The biophysics of water, has been debated over more than a century. Although its importance is still underestimated, significant breakthroughs occurred in recent years. The influence of protein condensation on water availability control was documented, new findings on water-transport proteins emerged, and the way water molecules rearrange to minimize free energy at interfaces was deciphered, influencing membrane thermodynamics. The state of knowledge continued to progress in the field of deep-sea marine biology, highlighting unknown effects of high hydrostatic pressure and/or temperature on interactions between proteins and ligands in extreme environments, and membrane structure adaptations. The role of osmolytes in protein stability control under stress is also discussed here in relation to fish egg hydration/buoyancy. The complexity of water movements within the cell is updated, all these findings leading to a better view of their impact on many cellular processes. The way water flow and osmotic gradients generated by ion transport work together to produce the driving force behind cell migration is also relevant to both marine biology and cancer research. Additional common points concern water dynamic changes during the neoplastic transformation of cells and tissues, or embryo development. This could improve imaging techniques, early cancer diagnosis, and understanding of the molecular and physiological basis of buoyancy for many marine species.

Flexible zinc-air batteries are the leading candidates as the next-generation power source for flexible/wearable electronics. However, constructing safe and high-performance solid-state electrolytes (SSEs) with intrinsic hydroxide ion (OH-) conduction remains a fundamental challenge. Herein, by adopting the natural and robust cellulose nanofibers (CNFs) as building blocks, the biomass SSEs with penetrating ion and water channels are constructed by knitting the OH--conductive CNFs and water-retentive CNFs together via an energy-efficient tape casting. Benefiting from the abundant ion and water channels with interconnected hydrated OH- wires for fast OH- conduction under a nanoconfined environment, the biomass SSEs reveal the high water-uptake, impressive OH- conductivity of 175 mS cm-1 and mechanical robustness simultaneously, which overcomes the commonly existed dilemma between ion conductivity and mechanical property. Remarkably, the flexible zinc-air batteries assemble with biomass SSEs deliver an exceptional cycle lifespan of 310 h and power density of 126 mW cm-2. The design methodology for water and ion channels opens a new avenue to design high-performance SSEs for batteries.

Demand for kidney grafts outpaces supply, limiting kidney transplantation as a treatment for kidney failure. Xenotransplantation has the potential to make kidney transplantation available to many more patients with kidney failure, but the ability of xenografts to support human physiologic homeostasis has not been established. A brain-dead adult decedent underwent bilateral native nephrectomies followed by 10 gene-edited (four gene knockouts, six human transgenes) pig-to-human xenotransplantation. Physiologic parameters and laboratory values were measured for seven days in a critical care setting. Data collection aimed to assess homeostasis by measuring components of the renin-angiotensin-aldosterone system, parathyroid hormone signaling, glomerular filtration rate, and markers of salt and water balance. Mean arterial blood pressure was maintained above 60 mmHg throughout. Pig kidneys secreted renin (post-operative day three to seven mean and standard deviation: 47.3 ± 9 pg/mL). Aldosterone and angiotensin II levels were present (post-operative day three to seven, 57.0 ± 8 pg/mL and 5.4 ± 4.3 pg/mL, respectively) despite plasma renin activity under 0.6 ng/mL/hr. Parathyroid hormone levels followed ionized calcium. Urine output down trended from 37 L to 6 L per day with 4.5 L of electrolyte free water loss on post-operative day six. Aquaporin 2 channels were detected in the apical surface of principal cells, supporting pig kidney response to human vasopressin. Serum creatinine down trended to 0.9 mg/dL by day seven. Glomerular filtration rate ranged 90-240 mL/min by creatinine clearance and single-dose inulin clearance. Thus, in a human decedent model, xenotransplantation of 10 gene-edited pig kidneys provided physiologic balance for seven days. Hence, our in-human study paves the way for future clinical study of pig-to-human kidney xenotransplantation in living persons.

Aquaporins (AQPs) allow the diffusion of hydrogen peroxide (H2O2) and act as ROS scavenging systems, which are important for controlling the redox state of cells. Recently, cerium oxide nanoparticles were found to increase the water and H2O2 permeability by modulating AQPs. To further analyze the action of nanoparticles (NPs) on AQP, we examined the effect of the NPs presenting different core compositions (CeO2, Gd2O3, Fe3O4, and TiO2), hydrodynamic sizes, and surface functionalization. The NPs produced an increase in H2O and H2O2 permeability as a general trend. The hydrodynamic sizes of the NPs in the range of 22-100 nm did not produce any significant effect. The chemical nature of the NPs\' core did not modify the effect and its intensity. On the other hand, the NPs\' functionalized surface plays a major role in influencing both water and H2O2 permeability. The results suggest that NPs can play a significant role in controlling oxidative stress in cells and might represent an innovative approach in the treatment of a number of pathologies associated with an increased oxidative status.

Despite of the major role of aquaporin (AQP) water channels in controlling transmembrane water fluxes, alternative ways for modulating water permeation have been proposed. In the Central Nervous System (CNS), Aquaporin-4 (AQP4) is reported to be functionally coupled with the calcium-channel Transient-Receptor Potential Vanilloid member-4 (TRPV4), which is controversially involved in cell volume regulation mechanisms and water transport dynamics. The present work aims to investigate the selective role of TRPV4 in regulating plasma membrane water permeability in an AQP4-independent way. Fluorescence-quenching water transport experiments in Aqp4-/- astrocytes revealed that cell swelling rate is significantly increased upon TRPV4 activation and in the absence of AQP4. The biophysical properties of TRPV4-dependent water transport were therefore assessed using the HEK-293 cell model. Calcein quenching experiments showed that chemical and thermal activation of TRPV4 overexpressed in HEK-293 cells leads to faster swelling kinetics. Stopped-flow light scattering water transport assay was used to measure the osmotic permeability coefficient (Pf, cm/s) and activation energy (Ea, kcal/mol) conferred by TRPV4. Results provided evidence that although the Pf measured upon TRPV4 activation is lower than the one obtained in AQP4-overexpressing cells (Pf of AQP4 = 0.01667 ± 0.0007; Pf of TRPV4 = 0.002261 ± 0.0004; Pf of TRPV4 + 4αPDD = 0.007985 ± 0.0006; Pf of WT = 0.002249 ± 0.0002), along with activation energy values (Ea of AQP4 = 0.86 ± 0.0006; Ea of TRPV4 + 4αPDD = 2.73 ± 1.9; Ea of WT = 8.532 ± 0.4), these parameters were compatible with a facilitated pathway for water movement rather than simple diffusion. The possibility to tune plasma membrane water permeability more finely through TRPV4 might represent a protective mechanism in cells constantly facing severe osmotic challenges to avoid the potential deleterious effects of the rapid cell swelling occurring via AQP channels.

The altered expression of known brain Aquaporin (AQP) channels 1, 4 and 9 has been correlated with neuropathological AD progression, but possible roles of other AQP classes in neurological disease remain understudied. The levels of transcripts of all thirteen human AQP subtypes were compared in healthy and Alzheimer\'s disease (AD) brains by statistical analyses of microarray RNAseq expression data from the Allen Brain Atlas database. Previously unreported, AQPs 0, 6 and 10, are present in human brains at the transcript level. Three AD-affected brain regions, hippocampus (HIP), parietal cortex (PCx) and temporal cortex (TCx), were assessed in three subgroups: young controls (n = 6, aged 24-57); aged controls (n = 26, aged 78-99); and an AD cohort (n = 12, aged 79-99). A significant positive correlation (p < 10-10) was seen for AQP transcript levels as a function of the subject\'s age in years. Differential expressions correlated with brain region, age, and AD diagnosis, particularly between the HIP and cortical regions. Interestingly, three classes of AQPs (0, 6 and 8) upregulated in AD compared to young controls are permeable to H2O2. Of these, AQPs 0 and 8 were increased in TCx and AQP6 in HIP, suggesting a role of AQPs in AD-related oxidative stress. The outcomes here are the first to demonstrate that the expression profile of AQP channels in the human brain is more diverse than previously thought, and transcript levels are influenced by both age and AD status. Associations between reactive oxygen stress and neurodegenerative disease risk highlight AQPs 0, 6, 8 and 10 as potential therapeutic targets.

Forward osmosis (FO) membranes have the advantages of low energy consumption, high water recovery rate, and low membrane pollution trend, and they have been widely studied in many fields. However, the internal concentration polarization (ICP) caused by the accumulation of solutes in the porous support layer will reduce permeation efficiency, which is currently unavoidable. In this paper, we doped Graphene oxide (GO) nanoparticles (50~150 nm) to a polyamide (PA) active layer and/or polysulfone (PSF) support layer, investigating the influence of GO on the morphology and properties of thin-film composite forward osmosis (TFC-FO) membranes. The results show that under the optimal doping amount, doping GO to the PA active layer and PSF support layer, respectively, is conducive to the formation of dense and uniform nano-scale water channels perpendicular to the membrane surface possessing a high salt rejection rate and low reverse solute flux without sacrificing high water flux. Moreover, the water channels formed by doping GO to the active layer possess preferable properties, which significantly improves the salt rejection and water permeability of the membrane, with a salt rejection rate higher than 99% and a water flux of 54.85 L·m-2·h-1 while the pure PSF-PA membrane water flux is 12.94 L·m-2·h-1. GO-doping modification is promising for improving the performance and structure of TFC-FO membranes.

Some aquaporins (AQPs) allow the diffusion of hydrogen peroxide (H2O2), the most abundant ROS, through the cell membranes. Therefore, the possibility of regulating the AQP-mediated permeability to H2O2, and thus ROS scavenging, appears particularly important for controlling the redox state of cells in physiological and pathophysiological conditions. Several compounds have been screened and characterized for this purpose. This study aimed to analyze the effect of cerium oxide nanoparticles (CNPs) presenting antioxidant activity on AQP functioning. HeLa cells express AQP3, 6, 8, and 11, able to facilitate H2O2. AQP3, 6, and 8 are expressed in the plasma membrane and intracellularly, while AQP11 resides only in intracellular structures. CNPs but not cerium ions treatment significantly increased the water and H2O2 permeability by interacting with AQP3, 6, and especially with AQP8. CNPs increased considerably the AQP-mediated water diffusion in cells with oxidative stress. Functional experiments with silenced HeLa cells revealed that CNPs increased the H2O2 diffusion mainly by modulating the AQP8 permeability but also the AQP3 and AQP6, even if to a lesser extent. Current findings suggest that CNPs represent a promising pharmaceutical agent that might potentially be used in numerous pathologies involving oxidative stress as tumors and neurodegenerative diseases.

We studied cell recruitment following optic tectum (OT) injury in zebrafish (Danio rerio), which has a remarkable ability to regenerate many of its organs, including the brain. The OT is the largest dorsal layered structure in the zebrafish brain. In juveniles, it is an ideal structure for imaging and dissection. We investigated the recruited cells within the juvenile OT during regeneration in a Pdgfrβ-Gal4:UAS-EGFP line in which pericytes, vascular, circulating, and meningeal cells are labeled, together with neurons and progenitors. We first performed high-resolution confocal microscopy and single-cell RNA-sequencing (scRNAseq) on EGFP-positive cells. We then tested three types of injury with very different outcomes (needle (mean depth in the OT of 200 µm); deep-laser (depth: 100 to 200 µm depth); surface-laser (depth: 0 to 100 µm)). Laser had the additional advantage of better mimicking of ischemic cerebral accidents. No massive recruitment of EGFP-positive cells was observed following laser injury deep in the OT. This type of injury does not perturb the meninx/brain-blood barrier (BBB). We also performed laser injuries at the surface of the OT, which in contrast create a breach in the meninges. Surprisingly, one day after such injury, we observed the migration to the injury site of various EGFP-positive cell types at the surface of the OT. The migrating cells included midline roof cells, which activated the PI3K-AKT pathway; fibroblast-like cells expressing numerous collagen genes and most prominently in 3D imaging; and a large number of arachnoid cells that probably migrate to the injury site through the activation of cilia motility genes, most likely being direct targets of the FOXJ1a gene. This study, combining high-content imaging and scRNAseq in physiological and pathological conditions, sheds light on meninges repair mechanisms in zebrafish that probably also operate in mammalian meninges.

Achiral 2-hydroxy-N-(diphenylmethyl)acetamide (HNDPA) crystallizes in the P61 chiral space group as a hydrate, building up permeable chiral crystalline helical water channels. The crystallization-driven chiral self-resolution process is highly robust, with the same air-stable crystalline form readily obtained under a variety of conditions. Interestingly, the HNDPA supramolecular helix inner pore is filled by a helical water wire. The whole edifice is mainly stabilized by robust hydrogen bonds involving the HNDPA amide bonds and CH… π interactions between the HNDPA phenyl groups. The crystalline structure shows breathing behavior, with completely reversible release and re-uptake of water inside the chiral channel under ambient conditions. Importantly, the HNDPA channel is able to transport water very efficiently and selectively under biomimetic conditions. With a permeability per channel of 3.3 million water molecules per second in large unilamellar vesicles (LUV) and total selectivity against NaCl, the HNDPA channel is a very promising functional nanomaterial for future applications.