Physicochemical control of solvation and molecular assembly of charged amphiphilic oligomers at air-aqueous interfaces.

HYPOTHESIS: Understanding the rules that control the assembly of nanostructured soft materials at interfaces is central to many applications. We hypothesize that electrolytes can be used to alter the hydration shell of amphiphilic oligomers at the air-aqueous interface of Langmuir films, thereby providing a means to control the formation of emergent nanostructures. EXPERIMENTS: Three representative salts - (NaF, NaCl, NaSCN) were studied for mediating the self-assembly of oligodimethylsiloxane methylimidazolium (ODMS-MIM+) amphiphiles in Langmuir films. The effects of the different salts on the nanostructure assembly of these films were probed using vibrational sum frequency generation (SFG) spectroscopy and Langmuir trough techniques. Experimental data were supported by atomistic molecular dynamic simulations. FINDINGS: Langmuir trough surface pressure - area isotherms suggested a surprising effect on oligomer assembly, whereby the presence of anions affects the stability of the interfacial layer irrespective of their surface propensities. In contrast, SFG results implied a strong anion effect that parallels the surface activity of anions. These seemingly contradictory trends are explained by anion driven tail dehydration resulting in increasingly heterogeneous systems with entangled ODMS tails and appreciable anion penetration into the complex interfacial layer comprised of headgroups, tails, and interfacial water molecules. These findings provide physical and chemical insight for tuning a wide range of interfacial assemblies.

Role of tumor-derived exosomes mediated immune cell reprograming in cancer.

Tumor-derived exosomes (TDEs), as topologies of tumor cells, not only carry biological information from the mother, but also act as messengers for cellular communication. It has been demonstrated that TDEs play a key role in inducing an immunosuppressive tumor microenvironment (TME). They can reprogram immune cells indirectly or directly by delivering inhibitory proteins, cytokines, RNA and other substances. They not only inhibit the maturation and function of dendritic cells (DCs) and natural killer (NK) cells, but also remodel M2 macrophages and inhibit T cell infiltration to promote immunosuppression and create a favorable ecological niche for tumor growth, invasion and metastasis. Based on the specificity of TDEs, targeting TDEs has become a new strategy to monitor tumor progression and enhance treatment efficacy. This paper reviews the intricate molecular mechanisms underlying the immunosuppressive effects induced by TDEs to establish a theoretical foundation for cancer therapy. Additionally, the challenges of TDEs as a novel approach to tumor treatment are discussed.

Active Dynamic Weighting for multi-domain adaptation.

Multi-source unsupervised domain adaptation aims to transfer knowledge from multiple labeled source domains to an unlabeled target domain. Existing methods either seek a mixture of distributions across various domains or combine multiple single-source models for weighted fusion in the decision process, with little insight into the distributional discrepancy between different source domains and the target domain. Considering the discrepancies in global and local feature distributions between different domains and the complexity of obtaining category boundaries across domains, this paper proposes a novel Active Dynamic Weighting (ADW) for multi-source domain adaptation. Specifically, to effectively utilize the locally advantageous features in the source domains, ADW designs a multi-source dynamic adjustment mechanism during the training process to dynamically control the degree of feature alignment between each source and target domain in the training batch. In addition, to ensure the cross-domain categories can be distinguished, ADW devises a dynamic boundary loss to guide the model to focus on the hard samples near the decision boundary, which enhances the clarity of the decision boundary and improves the model's classification ability. Meanwhile, ADW applies active learning to multi-source unsupervised domain adaptation for the first time, guided by dynamic boundary loss, proposes an efficient importance sampling strategy to select target domain hard samples to annotate at a minimal annotation budget, integrates it into the training process, and further refines the domain alignment at the category level. Experiments on various benchmark datasets consistently demonstrate the superiority of our method.

Anti-polyelectrolyte and polyelectrolyte effects on conformations of polyzwitterionic chains in dilute aqueous solutions.

Polyzwitterions (PZs) are considered as model synthetic analogs of intrinsically disordered proteins. Based on this analogy, PZs in dilute aqueous solutions are expected to attain either globular (i.e. molten, compact) or random coil conformations. Addition of salt is expected to open these conformations. To the best of our knowledge, these hypotheses about conformations of PZs have never been verified. In this study, we test these hypotheses by studying effects of added salt [potassium bromide (KBr)] on gyration and hydrodynamic radii of poly(sulfobetaine methacrylate) in dilute aqueous solutions using dynamic light scattering and small-angle X-ray scattering, respectively. Effects of zwitteration are revealed by direct comparisons of the PZs with the polymers of the same backbone but containing (1) no explicit charges on side groups such as poly(2-dimethylaminoethyl methacrylate)s and (2) explicit cationic side groups with tertiary amino bromide pendants. Zeta-potential measurements, transmission electron microscopy, and ab initio molecular dynamics simulations reveal that the PZs acquire net positive charge in near salt-free conditions due to protonation but retain coiled conformations. Added KBr leads to nonmonotonic changes exhibiting an increase followed by a decrease in radius of gyration (and hydrodynamic radius), which are called antipolyelectrolyte and polyelectrolyte effects, respectively. Charge regulation and screening of charge-charge interactions are discussed in relation to the antipolyelectrolyte and polyelectrolyte effects, respectively, which highlight the importance of salt in affecting net charge and conformations of PZs.

Evidence for long-term potentiation in phospholipid membranes.

Biological supramolecular assemblies, such as phospholipid bilayer membranes, have been used to demonstrate signal processing via short-term synaptic plasticity (STP) in the form of paired pulse facilitation and depression, emulating the brain's efficiency and flexible cognitive capabilities. However, STP memory in lipid bilayers is volatile and cannot be stored or accessed over relevant periods of time, a key requirement for learning. Using droplet interface bilayers (DIBs) composed of lipids, water and hexadecane, and an electrical stimulation training protocol featuring repetitive sinusoidal voltage cycling, we show that DIBs displaying memcapacitive properties can also exhibit persistent synaptic plasticity in the form of long-term potentiation (LTP) associated with capacitive energy storage in the phospholipid bilayer. The time scales for the physical changes associated with the LTP range between minutes and hours, and are substantially longer than previous STP studies, where stored energy dissipated after only a few seconds. STP behavior is the result of reversible changes in bilayer area and thickness. On the other hand, LTP is the result of additional molecular and structural changes to the zwitterionic lipid headgroups and the dielectric properties of the lipid bilayer that result from the buildup of an increasingly asymmetric charge distribution at the bilayer interfaces.

The Unexpected Role of Cations in the Self-Assembly of Positively Charged Amphiphiles at Liquid/Liquid Interfaces.

Conventional wisdom suggests that cations play a minimal role in the assembly of cationic amphiphiles. Here, we show that at liquid/liquid (L/L) interfaces, specific cation effects can modulate the assemblies of hydrophobic tails in an oil phase despite being attached to cationic headgroups in the aqueous phase. We used oligo-dimethylsiloxane (ODMS) methyl imidazolium amphiphiles to identify these specific interactions at hexadecane/aqueous interfaces. Small cations, such as Li+, bind to the O atoms in the ODMS tail and pin it to the interface, thereby imposing a kinked conformation─as evidenced by vibrational sum frequency generation spectroscopy and molecular dynamics simulations. While larger Cs+ ions more readily partition to the interface, they do not form analogous complexes. Our data not only point to ways for controlling amphiphile structure at L/L interfaces but also suggest a means for the separation of Li+, or related applications, in soft-matter electronics.

MST1 Suppresses Disturbed Flow Induced Atherosclerosis.

BACKGROUND: Atherosclerosis occurs mainly at arterial branching points exposed to disturbed blood flow. How MST1 (mammalian sterile 20-like kinase 1), the primary kinase in the mechanosensitive Hippo pathway modulates disturbed flow induced endothelial cells (ECs) activation and atherosclerosis remains unclear. METHODS: To assess the role of MST1 in vivo, mice with EC-specific Mst1 deficiency on ApoE-/- background (Mst1iECKOApoE-/-) were used in an atherosclerosis model generated by carotid artery ligation. Mass spectrometry, immunoprecipitation, proximity ligation assay, and dye uptake assay were used to identify the functional substrate of MST1. Human umbilical vein endothelial cells and human aortic endothelial cells were subjected to oscillatory shear stress that mimic disturbed flow in experiments conducted in vitro. RESULTS: We found that the phosphorylation of endothelial MST1 was significantly inhibited in oscillatory shear stress-exposed regions of human and mouse arteries and ECs. Ectopic lenti-mediated overexpression of wild-type MST1, but not a kinase-deficient mutant of MST1, reversed disturbed flow-caused EC activation and atherosclerosis in EC-specific Mst1 deficiency on ApoE-/- background (Mst1iECKOApoE-/-). Inhibition of MST1 by oscillatory shear stress led to reduced phosphorylation of Cx43 (connexin 43) at Ser255, the Cx43 hemichannel open, EC activation, and atherosclerosis, which were blocked by TAT-GAP19, a Cx43 hemichannel inhibitory peptide. Mass spectrometry studies identified that Filamin B fueled the translocation of Cx43 to lipid rafts for further hemichannel open. Finally, lenti-mediated overexpression of the Cx43S255 mutant into glutamate to mimic phosphorylation blunted disturbed flow-induced EC activation, thereby inhibiting the atherogenesis in both ApoE-/- and Mst1 iECKOApoE-/- mice. CONCLUSIONS: Our study reveals that inhibition of the MST1-Cx43 axis is an essential driver of oscillatory shear stress-induced endothelial dysfunction and atherosclerosis, which provides a new therapeutic target for the treatment of atherosclerosis.

Squeezing Out Interfacial Solvation: The Role of Hydrogen-Bonding in the Structural and Orientational Freedom of Molecular Self-Assembly.

Bioinspired membrane molecules with improved physical properties and enhanced stability can serve as functional models for conventional lipid or amphiphilic species. Importantly, these molecules can also provide new insights into emergent phenomena that manifest during self-assembly at interfaces. Here, we elucidate the structural response and mechanistic steps underlying the self-assembly of the amphiphilic, charged oligodimethylsiloxane imidazolium cation (ODMS-MIM+) at the air-aqueous interface using Langmuir trough methods with coincident surface-specific vibrational sum-frequency generation (SFG) spectroscopy. We find evidence for a new compression-induced desolvation step that precedes commonly known disordered-to-ordered phase transitions to form nanoscopic assemblies. The experimental data was supported by atomistic molecular dynamics (MD) simulations to provide a detailed mechanistic picture underlying the assembly and the role of water in these phase transitions. The sensitivity of the hydrophobic ODMS tail conformations to compression─owing to distinct water-ODMS interactions and tail-tail solvation properties─offers new strategies for the design of interfaces that can be further used to develop soft-matter electronics and low-dimensional materials using physical and chemical controls.

Rapid Access to Giant Unilamellar Liposomes with Upper Size Control: Membrane-Gated, Gel-Assisted Lipid Hydration.

Combining gel-assisted lipid hydration with membrane-based lipid extrusion, we demonstrate here a general procedure for rapid preparation of giant unilamellar liposomes with upper size control. Featured in this procedure are planar lipid stacks deposited on poly(vinyl alcohol) gel, which are further laminated atop with microporous polycarbonate membranes. Control of liposome size is thus realized through the uniform-sized pores of the latter, which provide the only access for the underlying lipids to enter the main aqueous phase upon hydration. Production of both single-phased and biphasic (Janus) liposomes using several commonly employed model lipids, including 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) and cholesterol, is presented. The size distribution, yield and lamellarity of these liposome products are characterized and analyzed in detail by confocal fluorescence microscopy. This procedure thus offers a simple and fast alternative route to giant unilamellar liposomes with upper size control.

Dipolar Janus liposomes: formation, electrokinetic motion and self-assembly.

Presented herein is the first report on dipolar Janus liposomes-liposomes that contain opposite surface charges decorating the two hemispheres of the same colloidal body. Such heterogeneous organization of surface charge is achieved through cholesterol-modulated lipid phase separation, which sorts anionic/cationic lipids into coexisting liquid-ordered/liquid-disordered domains. We present optimized experimental conditions to produce these liposomes in high yields, based on the gel-assisted hydration of ternary lipid systems consisting of cholesterol, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, and 1,2-dioleoyl-sn-glycero-3-phosphocholine. The size/charge distribution and domain configuration of these liposomes are characterized in detail by confocal fluorescence microscopy, nanosphere binding and zeta potential measurements. Using confocal fluorescence microscopy, we also follow the electrokinetic motion as well as the electrostatic self-assembly of these new dipolar Janus particles.

Janus Liposomes: Gel-Assisted Formation and Bioaffinity-Directed Clustering.

This article reports a high-yield procedure for preparing microsized (giant) Janus liposomes via gel-assisted lipid swelling and clustering behavior of these liposomes directed by biotin-avidin affinity binding. Confocal fluorescence microscopy reveals in detail that these new lipid colloidal particles display broken symmetry and heterogeneous surface chemistry similar to other types of Janus particles. An optimized formation procedure is presented, which reproducibly yields large liposome populations dominated by a single-domain configuration. This work further demonstrates that biotin-conjugated 1,2-dioleoyl- sn-glycero-3-phosphoethanolamine preferentially partitions into the liquid-disordered phase of the lipid matrix, rendering these Janus liposomes asymmetrical binding capacity toward avidin. This affinity binding drives irreversible and domain-specific cluster formation among Janus liposomes, whose structure and size are found to depend on the domain configuration of individual liposomes and incubation time.

Rational Design of Wide Spectral-Responsive Heterostructures of Au Nanorod Coupled Ag3PO4 with Enhanced Photocatalytic Performance.

Noble metallic nanomaterials with surface plasmon resonance (SPR) effects and hot electron cell effects open new opportunities for designing efficient visible-light-driven hybrid photocatalysts. In this work, we reported a broadband visible-light responsive photocatalyst by incorporating Au nanorods (AuNRs) into Ag3PO4 nanostructures. The longitudinal plasma of AuNRs enabled AuNRs/Ag3PO4 heterostructures to harvest light energy up to 800 nm. The obtained AuNRs/Ag3PO4 hybrid exhibited enhanced photocatalytic efficiency toward the degradation of rhodamine B (RhB) under solar irradiation. Ag3PO4, RhB, and AuNRs played different roles according to the distinct optical properties of each individual component. The dominant photocatalytic process in the different light regions were divided as follows: direct excitation of Ag3PO4 for λ ≥ 420 nm, RhB sensitization for λ ≥ 550 nm, and SPR effect for λ ≥ 600 nm. The relationship between the pathway of charge transfer and the photocatalytic activity of the AuNRs/Ag3PO4 heterostructures was investigated systematically, revealing the specific role of AuNRs in regulating the photocatalytic activity. This work presents an innovative strategy for determining the comprehensive function of the SPR effect in relevant semiconductor-based photocatalysis and functional nanodevices with a broadband light responses.

Voxel-based, brain-wide association study of aberrant functional connectivity in schizophrenia implicates thalamocortical circuitry.

BACKGROUND: Wernicke's concept of 'sejunction' or aberrant associations among specialized brain regions is one of the earliest hypotheses attempting to explain the myriad of symptoms in psychotic disorders. Unbiased data mining of all possible brain-wide connections in large data sets is an essential first step in localizing these aberrant circuits. METHODS: We analyzed functional connectivity using the largest resting-state neuroimaging data set reported to date in the schizophrenia literature (415 patients vs. 405 controls from UK, USA, Taiwan, and China). An exhaustive brain-wide association study at both regional and voxel-based levels enabled a continuous data-driven discovery of the key aberrant circuits in schizophrenia. RESULTS: Results identify the thalamus as the key hub for altered functional networks in patients. Increased thalamus-primary somatosensory cortex connectivity was the most significant aberration in schizophrenia (P=10(-18)). Overall, a number of thalamic links with motor and sensory cortical regions showed increased connectivity in schizophrenia, whereas thalamo-frontal connectivity was weakened. Network changes were correlated with symptom severity and illness duration, and support vector machine analysis revealed discrimination accuracies of 73.53-80.92%. CONCLUSIONS: Widespread alterations in resting-state thalamocortical functional connectivity is likely to be a core feature of schizophrenia that contributes to the extensive sensory, motor, cognitive, and emotional impairments in this disorder. Changes in this schizophrenia-associated network could be a reliable mechanistic index to discriminate patients from healthy controls.

Colorimetric detection of Hg²+ ions in aqueous media using CA-Au NPs.

Based on the selective interaction between Hg(2+) ions and cyanuric acid (CA) and the anti-aggregation of CA stabilized gold nanoparticles (CA-Au NPs), a simple colorimetric method was developed for detecting Hg(2+) ions. In a medium of pH 7.4 tris-HCl buffer containing 8×10(-3) M NaCl, the CA-Au NPs solution was red, which was due to CA adsorbed onto the surface of Au NPs, stabilizing Au NPs against aggregation. When CA-Hg(II)-CA complex was formed in the presence of Hg(2+), the stability of CA-Au NPs reduced, and then aggregation of Au NPs occurred. Consequently, the color of the solution changed from red to blue and could easily be measured with a common spectrophotometer. The aggregation of Au NPs was also validated using transmission electron microscopy (TEM). The controlled experiment showed that other ions including Ba(2+), Ca(2+), Zn(2+), Cd(2+), Co(2+), Mn(2+), Cu(2+), Mg(2+), and Ni(2+) ions did not induce any distinct spectral changes, which constituted a Hg(2+)-selective sensor. A dynamic range of 1.6-16×10(-6)M Hg(2+) ions was observed at the optimized reaction condition. This method provides a potentially useful tool for Hg(2+) detection.