Post-stroke cognitive impairment: exploring molecular mechanisms and omics biomarkers for early identification and intervention.

Post-stroke cognitive impairment (PSCI) is a major stroke consequence that has a severe impact on patients' quality of life and survival rate. For this reason, it is especially crucial to identify and intervene early in high-risk groups during the acute phase of stroke. Currently, there are no reliable and efficient techniques for the early diagnosis, appropriate evaluation, or prognostication of PSCI. Instead, plenty of biomarkers in stroke patients have progressively been linked to cognitive impairment in recent years. High-throughput omics techniques that generate large amounts of data and process it to a high quality have been used to screen and identify biomarkers of PSCI in order to investigate the molecular mechanisms of the disease. These techniques include metabolomics, which explores dynamic changes in the organism, gut microbiomics, which studies host-microbe interactions, genomics, which elucidates deeper disease mechanisms, transcriptomics and proteomics, which describe gene expression and regulation. We looked through electronic databases like PubMed, the Cochrane Library, Embase, Web of Science, and common databases for each omics to find biomarkers that might be connected to the pathophysiology of PSCI. As all, we found 34 studies: 14 in the field of metabolomics, 5 in the field of gut microbiomics, 5 in the field of genomics, 4 in the field of transcriptomics, and 7 in the field of proteomics. We discovered that neuroinflammation, oxidative stress, and atherosclerosis may be the primary causes of PSCI development, and that metabolomics may play a role in the molecular mechanisms of PSCI. In this study, we summarized the existing issues across omics technologies and discuss the latest discoveries of PSCI biomarkers in the context of omics, with the goal of investigating the molecular causes of post-stroke cognitive impairment. We also discuss the potential therapeutic utility of omics platforms for PSCI mechanisms, diagnosis, and intervention in order to promote the area's advancement towards precision PSCI treatment.

Molecular interaction mechanism for humic acids fouling resistance on charged, zwitterion-like and zwitterionic surfaces.

Humic acids (HA) are ubiquitous in surface waters, leading to significant fouling challenges. While zwitterion-like and zwitterionic surfaces have emerged as promising candidates for antifouling, a quantitative understanding of molecular interaction mechanism, particularly at the nanoscale, still remains elusive. In this work, the intermolecular forces between HA and charged, zwitterion-like or zwitterionic monolayers in aqueous environments were quantified using atomic force microscope. Compared to cationic MTAC ([2-(methacryloyloxy)ethyl]trimethylammonium chloride), which exhibited an adhesion energy of âˆ¼1.342 mJ/m2 with HA due to the synergistic effect of electrostatic attraction and possible cation-π interaction, anionic SPMA (3-sulfopropyl methacrylate) showed a weaker adhesion energy (∼0.258 mJ/m2) attributed to the electrostatic repulsion. Zwitterion-like MTAC/SPMA mixture, driven by electrostatic attraction between opposite charges, formed a hydration layer that prevented the interaction with HA, thereby considerably reducing adhesion energy to âˆ¼0.123 mJ/m2. In contrast, zwitterionic MPC (2-methacryloyloxyethyl phosphorylcholine) and DMAPS ([2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl) ammonium hydroxide) displayed ultralow adhesion energy (0.06-0.07 mJ/m2) with HA, arising from their strong dipole moments which could induce a tight hydration layer that effectively inhibited HA fouling. The pH-mediated electrostatic interaction resulted in the increased adhesion energy for MTAC but decreased adhesion energy for SPMA with elevated pH, while the adhesion energy for zwitterion-like and zwitterionic surfaces was independent of environmental pH. Density functional theory (DFT) simulation confirmed the strong binding capability of MPC and DMAPS with water molecules (∼-12 kcal mol-1). This work provides valuable insights into the molecular interaction mechanisms underlying humic-substance-fouling resistance of charged, zwitterion-like and zwitterionic materials at the nanoscale, shedding light on developing more effective strategy for HA antifouling in water treatment.

Determining individual suitability for neoadjuvant systemic therapy in breast cancer patients through deep learning.

BACKGROUND: The survival advantage of neoadjuvant systemic therapy (NST) for breast cancer patients remains controversial, especially when considering the heterogeneous characteristics of individual patients. OBJECTIVE: To discern the variability in responses to breast cancer treatment at the individual level and propose personalized treatment recommendations utilizing deep learning (DL). METHODS: Six models were developed to offer individualized treatment suggestions. Outcomes for patients whose actual treatments aligned with model recommendations were compared to those whose did not. The influence of certain baseline features of patients on NST selection was visualized and quantified by multivariate logistic regression and Poisson regression analyses. RESULTS: Our study included 94,487 female breast cancer patients. The Balanced Individual Treatment Effect for Survival data (BITES) model outperformed other models in performance, showing a statistically significant protective effect with inverse probability treatment weighting (IPTW)-adjusted baseline features [IPTW-adjusted hazard ratio: 0.51, 95% confidence interval (CI), 0.41-0.64; IPTW-adjusted risk difference: 21.46, 95% CI 18.90-24.01; IPTW-adjusted difference in restricted mean survival time: 21.51, 95% CI 19.37-23.80]. Adherence to BITES recommendations is associated with reduced breast cancer mortality and fewer adverse effects. BITES suggests that patients with TNM stage IIB, IIIB, triple-negative subtype, a higher number of positive axillary lymph nodes, and larger tumors are most likely to benefit from NST. CONCLUSIONS: Our results demonstrated the potential of BITES to aid in clinical treatment decisions and offer quantitative treatment insights. In our further research, these models should be validated in clinical settings and additional patient features as well as outcome measures should be studied in depth.

Nanoscale Insights into the Interaction Mechanism Underlying the Adsorption and Retention of Heavy Metal Ions by Humic Acid.

The mobility and distribution of heavy metal ions (HMs) in aquatic environments are significantly influenced by humic acid (HA), which is ubiquitous. A quantitative understanding of the interaction mechanism underlying the adsorption and retention of HMs by HA is of vital significance but remains elusive. Herein, the interaction mechanism between HA and different types of HMs (i.e., Cd(II), Pb(II), arsenate, and chromate) was quantitatively investigated at the nanoscale. Based on quartz crystal microbalance with dissipation tests, the adsorption capacities of Pb(II), Cd(II), As(V), and Cr(VI) ionic species on the HA surface were measured as ∼0.40, ∼0.25, ∼0.12, and ∼0.02 nmol cm-2, respectively. Atomic force microscopy force results showed that the presence of Pb(II)/Cd(II) cations suppressed the electrostatic double-layer repulsion during the approach of two HA surfaces and the adhesion energy during separation was considerably enhanced from ∼2.18 to ∼5.05/∼4.18 mJ m-2. Such strong adhesion stems from the synergistic metal-HA complexation and cation-π interaction, as evidenced by spectroscopic analysis and theoretical simulation. In contrast, As(V)/Cr(VI) oxo-anions could form only weak hydrogen bonds with HA, resulting in similar adhesion energies for HA-HA (∼2.18 mJ m-2) and HA-As(V)/Cr(VI)-HA systems (∼2.26/∼1.96 mJ m-2). This work provides nanoscale insights into quantitative HM-HA interactions, improving the understanding of HMs biogeochemical cycling.

Molecular Insights into the Interaction Mechanism Underlying the Aggregation of Humic Acid and Its Adsorption on Clay Minerals.

Humic acid (HA) is ubiquitous in both terrestrial and aquatic environments, and understanding the molecular interaction mechanisms underlying its aggregation and adsorption is of vital significance. However, the intermolecular interactions of HA-HA and HA-clay mineral systems in complex aqueous environments remain elusive. Herein, the interactions of HA with various model surfaces (i.e., HA, mica, and talc) were quantitatively measured in aqueous media at the nanoscale using an atomic force microscope. The HA-HA interaction was found to be purely repulsive during surface approach, consistent with free energy calculation; during retraction, pH-dependent adhesion was observed due to the protonation/deprotonation of HA that influences the formation of hydrogen bonds. Different from the mica case, hydrophobic interaction was detected for the HA-talc system at pH 5.8, contributing to the stronger HA-talc adhesion, as also evidenced by adsorption results. Notably, HA-mica adhesion strongly depended on the loading force and contact time, most likely because of the short-range and time-dependent interfacial hydrogen bonding interaction under confinement, as compared to the dominant hydrophobic interaction for the HA-talc case. This study provides quantitative insights into the fundamental molecular interaction mechanisms underlying the aggregation of HA and its adsorption on clay minerals of varying hydrophobicity in environmental processes.

Signal recovery in optical wireless communication using photonic convolutional processor.

Deep neural networks (DNNs) have been applied to recover signals in optical communication systems and have shown competence of mitigating linear and nonlinear distortions. However, as the data throughput increases, the heavy computational cost of DNNs impedes them from rapid and power-efficient processing. In this paper, we propose an optical communication signal recovery technology based on a photonic convolutional processor, which is realized by dispersion delay unit and wavelength division multiplexing. Based on the photonic convolutional processor, we implement an optoelectronic convolutional neural network (OECNN) for signal post-equalization and experimentally demonstrate on 16QAM and 32QAM of an optical wireless communication system. With system parameters optimization, we verify that the OECNN can achieve accurate signal recovery where the bit error ratio (BER) is below the 7% forward error correction threshold of 3.8×10-3 at 2Gbps. With adding the OECNN-based nonlinear compensation, compared with only linear compensation, we improve the quality (Q) factor by 3.35 dB at 16QAM and 3.30 dB at 32QAM, which is comparable to that of an electronic neural network. This work proves that the photonic implementation of DNN is promising to provide a fast and power-efficient solution for optical communication signal processing.

Surface interaction mechanisms in mineral flotation: Fundamentals, measurements, and perspectives.

As non-renewable natural resources, minerals are essential in a broad range of biological and technological applications. The surface interactions of mineral particles with other objects (e.g., solids, bubbles, reagents) in aqueous suspensions play a critical role in mediating many interfacial phenomena involved in mineral flotation. In this work, we have reviewed the fundamentals of surface forces and quantitative surface property-force relationship of minerals, and the advances in the quantitative measurements of interaction forces of mineral-mineral, bubble-mineral and mineral-reagent using nanomechanical tools such as surface forces apparatus (SFA) and atomic force microscope (AFM). The quantitative correlation between surface properties of minerals at the solid/water interface and their surface interaction mechanisms with other objects in complex aqueous media at the nanoscale has been established. The existing challenges in mineral flotation such as characterization of anisotropic crystal plane or heterogeneous surface, low recovery of fine particle flotation, and in-situ electrochemical characterization of collectorless flotation as well as the future work to resolve the challenges based on the understanding and modulation of surface forces of minerals have also been discussed. This review provides useful insights into the fundamental understanding of the intermolecular and surface interaction mechanisms involved in mineral processing, with implications for precisely modulating related interfacial interactions towards the development of highly efficient industrial processes and chemical additives.

Nanomechanical Insights into Versatile Polydopamine Wet Adhesive Interacting with Liquid-Infused and Solid Slippery Surfaces.

Mussel-inspired polydopamine (PDA) can be readily deposited on almost all kinds of substrates and possesses versatile wet adhesion. Meanwhile, slippery surfaces have attracted much attention for their self-cleaning capabilities. It remains unclear how the versatile PDA adhesive would interact with slippery surfaces. In this work, both liquid-infused poly(tetrafluoroethylene) (PTFE) (LI-PTFE) and solid slippery surfaces (i.e., self-assembly of small thiol-terminated organosilane, polysiloxane covalently attached to substrates) were fabricated to investigate their capability to prevent PDA deposition. It was found that PDA particles could be easily deposited on a PTFE membrane and the two types of solid slippery surfaces, which resulted in the alternation of their surface wettability and slippery behavior of water droplets. Adhesion was detected between a PDA-coated silica colloidal probe and the PTFE membrane or solid slippery surfaces through quantitative force measurements using an atomic force microscope (AFM), mainly due to van der Waals (vdW) and hydrophobic interactions, which led to the PDA deposition phenomenon. In contrast, LI-PTFE with a thin liquid lubricant film could effectively prevent PDA deposition, with negligible changes in surface morphology, wettability, and slippery characteristics. Although PDA particles could be loosely attached to the lubricant/water interface for LI-PTFE based on the capillary adhesion measured by AFM, they could be readily removed by gentle rinsing with water, as demonstrated by the ultralow friction over LI-PTFE as compared to PTFE using lateral force microscopy (LFM). Our results indicate that LI-PTFE possesses excellent antifouling and self-cleaning properties even when interacting with the versatile PDA wet adhesives. This work provides new insights into the deposition of PDA on slippery surfaces and their interaction mechanism at the nanoscale, with useful implications for the design and development of novel slippery surfaces.

Probing the intermolecular interaction mechanisms between humic acid and different substrates with implications for its adsorption and removal in water treatment.

Humic substance is a ubiquitous class of natural organic matter (NOM) in soil and aquatic ecosystems, which severely affects the terrestrial and aquatic environments as well as water-based engineering systems by adsorption on solids (e.g., soil minerals, nanoparticles, membranes) via different interaction mechanisms. Herein, the chemical force microscopy (CFM) technique was employed to quantitatively probe the intermolecular forces of humic acid (HA, a representative humic substance) interacting with self-assembled monolayers (SAMs, i.e., OH-SAMs, CH3-SAMs, NH2-SAMs and COOH-SAMs) in various aqueous environments at the nanoscale. The interaction forces measured during approach could be well fitted by the extended Derjaguin-Landau-Verwey-Overbeek (DLVO) theory by incorporating the hydrophobic interaction. The average adhesion energy followed the trend as: NH2-SAMs (∼3.11 mJ/m2) > CH3-SAMs (∼2.03 mJ/m2) > OH-SAMs (∼1.38 mJ/m2) > COOH-SAMs (∼0.52 mJ/m2) in 100 mM NaCl at pH 5.8, indicating the significant role of electrostatic attraction in contributing to the HA adhesion, followed by hydrophobic interaction and hydrogen bonding. The adhesion energy was found to be dependent on NaCl concentration, Ca2+ addition and pH. For the interaction between NH2-SAMs and HA, their electrostatic attraction at pH 5.8 turned to repulsion under alkaline condition which led to the sudden drop of adhesion energy. Such results promised the adsorption and release of HA using the recyclable magnetic Fe3O4 nanoparticles coated with (3-aminopropyl)tiethoxysilane (APTES). This work provides quantitative information on the molecular interaction mechanism underlying the adsorption of HA on solids of varying surface chemistry at the nanoscale, with useful implications for developing effective chemical additives to remove HA in water treatment and many other engineering processes.

Interfacial behavior and interaction mechanism of pentol/water interface stabilized with asphaltenes.

Emulsions stabilized with asphaltenes are undesirable in oil production due to the challenges associated with fouling, corrosion and environment contaminations. To understand the stabilization mechanism, the interfacial behavior and interaction mechanism of pentol/water interface in the presence of asphaltenes were investigated by interfacial tension (IFT) and atomic force microscopy (AFM) force measurements. The measured IFT increases as NaCl concentration increases from 0 to 3 M, and decreases as asphaltenes concentration increases from 50 to 1000 ppm. The drop probe AFM force measurements between two water droplets in pentol with interfacial asphaltenes show attraction during approach attributed to the solvophobic interaction. During retraction, interfacial adhesion Fadh/R is measured arising from the contact and interpenetration or local aggregation of asphaltenes molecules. Fadh/R gradually decreases with the increase of NaCl concentration, originated from the enhanced steric repulsion due to the accumulation of more asphaltenes at pentol/water interface with addition of salts. With increasing asphaltenes concentration, Fadh/R keeps decreasing due to the self-aggregation of large amounts of asphaltenes molecules at the interface. This work provides useful information on the stabilization mechanism of pentol/water interface with adsorbed asphaltenes, with implications for developing effective technologies or products to solve the challenging emulsion issues.

A two-step flocculation process on oil sands tailings treatment using oppositely charged polymer flocculants.

Water management and treatment of mineral tailings and oil sands tailings are becoming critical challenges for the sustainable development of natural resources. Polymeric flocculants have been widely employed to facilitate the flocculation and settling of suspended fine solid particles in tailings, resulting in the separation of released water and solid sediments. In this study, a new flocculation process was developed for the treatment of oil sands tailings by using two oppositely charged polymers, i.e. an anionic polyacrylamide and a natural cationic biopolymer, chitosan. The new process was able to not only improve the clarity of supernatant after settling but also achieve a high settling efficiency. Treatment of the oil sands tailings using pure anionic polyacrylamide showed relatively high initial settling rate (ISR) of ~10.3m/h but with poor supernatant clarity (>1000NTU); while the treatment using pure cationic polymer resulted in clear supernatant (turbidity as low as 22NTU) but relatively low ISR of >2m/h. In the new flocculation process, the addition of anionic polyacrylamide to the tailings was followed by a cationic polymer, which showed both a high ISR (~7.7m/h) and a low turbidity (71NTU) of the supernatant. The flocculation mechanism was further investigated via the measurements of floc size, zeta potential and surface forces. The new flocculation process was revealed to include two steps: (1) bridging of fine solids by anionic polyacrylamide, and (2) further aggregation and flocculation mediated by charge neutralisation of the cationic polymer, which significantly eliminated the fine solids in the supernatants as well as increases floc size. Our results provide insights into the basic understanding of the interactions between polymer flocculants and solid particles in tailings treatment, as well as the development of novel tailings treatment technologies.

Probing the interaction between air bubble and sphalerite mineral surface using atomic force microscope.

The interaction between air bubbles and solid surfaces plays important roles in many engineering processes, such as mineral froth flotation. In this work, an atomic force microscope (AFM) bubble probe technique was employed, for the first time, to directly measure the interaction forces between an air bubble and sphalerite mineral surfaces of different hydrophobicity (i.e., sphalerite before/after conditioning treatment) under various hydrodynamic conditions. The direct force measurements demonstrate the critical role of the hydrodynamic force and surface forces in bubble-mineral interaction and attachment, which agree well with the theoretical calculations based on Reynolds lubrication theory and augmented Young-Laplace equation by including the effect of disjoining pressure. The hydrophobic disjoining pressure was found to be stronger for the bubble-water-conditioned sphalerite interaction with a larger hydrophobic decay length, which enables the bubble attachment on conditioned sphalerite at relatively higher bubble approaching velocities than that of unconditioned sphalerite. Increasing the salt concentration (i.e., NaCl, CaCl2) leads to weakened electrical double layer force and thereby facilitates the bubble-mineral attachment, which follows the classical Derjaguin-Landau-Verwey-Overbeek (DLVO) theory by including the effects of hydrophobic interaction. The results provide insights into the basic understanding of the interaction mechanism between bubbles and minerals at nanoscale in froth flotation processes, and the methodology on probing the interaction forces of air bubble and sphalerite surfaces in this work can be extended to many other mineral and particle systems.

The protein kinase Hal5p is the high-copy suppressor of lithium-sensitive mutations of genes involved in the sporulation and meiosis as well as the ergosterol biosynthesis in Saccharomyces cerevisiae.

From a genome-scale genetic screen, we have identified 114 lithium-sensitive and 6 lithium-tolerant gene mutations in Saccharomyces cerevisiae. Twenty-five of these identified lithium-sensitive mutations are of genes previously reported to be involved in sporulation and meiosis, whereas thirty-six of them are of genes involved in the vacuolar protein sorting (VPS) pathway, mainly functioning in the membrane docking and fusion. Accordingly, the lithium-sensitive phenotypes for one third of identified VPS mutants well correlate to their intracellular lithium contents in response to lithium stress. This indicates the integrity of the VPS pathway is critic for the ion homeostasis in yeast cells. The halotolerant protein kinase Hal5p, a regulator of the potassium transporter Trk1p, is shown to be the high-copy suppressor of nearly one third of identified lithium-sensitive mutations of genes involved in the sporulation and meiosis as well as in the biosynthesis of ergosterol. These results suggest that Hal5p-mediated ion homeostasis is important for these two biological processes.