Potassium homeostasis is maintained primarily by the kidney, yet potassium is increasingly recognized not only as a regulated electrolyte but also as a key determinant of renal physiology and kidney health. Experimental, epidemiologic, and clinical evidence supports a reciprocal relationship in which kidney function governs potassium balance, whereas dietary potassium intake and plasma potassium concentration influence renal sodium transport, blood pressure regulation, and susceptibility to kidney injury. Both potassium deficiency and excess are associated with adverse cardiorenal outcomes, emphasizing the importance of maintaining potassium within an optimal physiologic range. Evidence suggests that the kidney adapts to changes in potassium availability through coordinated feedforward and feedback mechanisms, including a putative gut-kidney signaling axis and nephron-intrinsic potassium-sensing pathways. Along the nephron, inwardly rectifying potassium channels function as extracellular potassium sensors that couple changes in potassium concentration to alterations in epithelial transport and metabolism. Recent studies have identified potassium-responsive signaling pathways in the proximal tubule that regulate sodium transport, cellular growth, and kidney injury during potassium deficiency. In the distal convoluted tubule, related mechanisms regulate the thiazide-sensitive sodium-chloride cotransporter through the renal "potassium switch," linking potassium balance to sodium handling and blood pressure control. These mechanistic advances have renewed interest in potassium supplementation and potassium-containing additives as therapeutic interventions. Epidemiologic and emerging clinical data suggest that physiologically appropriate potassium intake, particularly from potassium-rich diets or bicarbonate/citrate-containing supplements, may provide cardiovascular and renal benefits. However, because impaired potassium excretion increases susceptibility to hyperkalemia in advanced chronic kidney disease, potassium supplementation and restriction should be individualized according to kidney function and patient risk.

Mole-rats are subterranean rodents with sensory and physiological adaptations to life in underground tunnels, yet their neurobiology remains largely unexplored. We present methods for in vivo electrophysiological recordings in awake, head-fixed, and freely moving African mole-rats (Fukomys anselli and Fukomys micklemi), addressing their unique anatomy and physiology. We report anesthesia, analgesia, and surgical procedures and find that elevated carbon dioxide concentrations are beneficial for recovery, likely due to a mutation in the potassium-chloride symporter KCC2. We also present a stereotaxic mole-rat brain atlas to guide electrode placement. Using tetrodes and silicon probes, we recorded single-unit activity and local field potentials in the cortex, hippocampus, and superior colliculus. Lastly, we present combined tissue clearing, light-sheet imaging, rehydration, and vibratome sectioning to enable 3D and 2D probe-track analyses within the same brain. The methodology will facilitate comparative studies among subterranean rodents, including the naked mole-rat (Heterocephalus glaber), to elucidate neurobiological adaptations to dark subterranean environments.

Deep eutectic solvents of type III, such as reline, a mixture of choline chloride and urea, are a relatively new class of green solvents that display physical properties intermediate between conventional salt solutions and ionic liquids. Well-established models used to explain colloidal stability and macromolecule conformation in usual solvents, including the hydrophobic effect and the formation of the electrical double layer, are not applicable to these solvents and their mixtures with water due to strong nonideal behavior and high ionic strength of those solvents. Hence, in this work, molecular dynamics simulations were performed to evaluate the thermodynamic stability of sodium dodecyl sulfate micelles in reline/water mixtures with different compositions by potential of mean force calculations and splitting the contributions from the surfactant ionic head and the hydrophobic tail. The presence of reline reduces the favorable contribution of the surfactant alkyl tail to aggregation, indicating a reduction of the hydrophobic effect, which is explained by a smaller number of water molecules in contact with the surfactant. However, the high adsorption of choline cations over the micelle surface also reduces the repulsion between the charged heads. The second effect dominates over the reduction of the hydrophobic effect, resulting in a more negative aggregation free energy and improved micelle stability in the presence of reline. The electrostatic potential from the anionic micelle was also computed and does not follow the usual electrical double layer models, presenting oscillations away from the micelle surface in mixtures with high reline concentration and with the choline cations almost completely replacing the sodium counterions from the micelle surface.

Currently, the time-averaged root-mean-square RF field (B1+rms) and specific absorption rate (SAR) are being evaluated to monitor and control RF-induced heating near conductive metallic implants, such as deep brain stimulation (DBS) leads, during MRI. However, experimental methods to assess the relationship between RF power, B1+rms, and SAR are lacking for RF coils, RF pulse sequences, metallic implants, and ionic solutions. A method is developed to evaluate the variation in RF power, B1+rms, and SAR with RF coils, metallic implants, and ionic solutions using phantoms consisting of water (H2O) and sodium chloride (NaCl) with four ionic concentrations (0, 1, 2, 3%), four metallic wavelengths (0, λ/2, λ, 2λ), two RF coils (body, head), transmit/receive (Tx/Rx) combinations, and five RF pulse flip angles (30, 45, 60, 75, 90 degrees) in two B0 fields (1.5T and 3T). The scanner-reported RF power and SAR varied with RF pulse sequences, RF coils, Tx/Rx, metallic implants, and ionic solutions, whereas B1+rms varied only with RF pulse sequences. The RF power, B1+rms, and SAR relationship depends on RF pulse sequences, RF coils, Tx/Rx, metallic implant wavelengths, and ionic concentrations. SAR (whole-body, head) scaled with RF power by absorption ratios (α) variable with experimental conditions.

Inflammatory bowel disease (IBD) is characterized by aberrant immune responses in the gut. Mas-related G protein-coupled receptor D (MrgprD), which is primarily expressed in sensory neurons of the dorsal root ganglia (DRG), is known to promote neuroinflammation. However, its potential role in driving intestinal inflammation remains undefined. Here, we show that systemic Mrgprd KO alleviated dextran sodium sulfate (DSS)-induced acute colitis. We found that MrgprD was expressed in colonic macrophages and DSS treatment increased its expression. Mrgprd global deletion reduced macrophage infiltration in the colon and suppressed their pro-inflammatory M1 polarization following DSS challenge. Using conditional KO mouse lines, we further demonstrate that myeloid-specific Mrgprd deletion conferred stronger protection than its neuronal deletion. This is evidenced by preserved colon length, reduced histopathology scores, improved barrier integrity, and decreased M1 macrophage proportions. Notably, neuron-specific, but not myeloid-specific, Mrgprd KO accelerated intestinal motility under physiological conditions. MrgprD deficiency reduced M1-associated gene expression and suppressed NF-κB signaling activation in both colonic lamina propria cells and bone marrow-derived macrophages (BMDMs), whereas activation of MrgprD by its agonist enhanced these responses in BMDMs. Bioinformatic analysis further supports the involvement of the MRGPRD-NF-κB signaling axis in human IBD. Collectively, our findings identify MrgprD as a novel driver of acute colitis, acting primarily through NF-κB-mediated pro-inflammatory macrophage polarization in the colon. © 2026 The Pathological Society of Great Britain and Ireland.

Opiranserin (VVZ-149) is a novel non-opioid, non-steroidal intravenous analgesic with triple antagonistic activity at glycine transporter 2 (GlyT2), purine 2 receptor 3 (P2X3), and serotonin receptor (5-HT2A). Its half-maximal inhibitory concentrations are 0.86, 0.87, and 1.3 μM for GlyT2, P2X3, and 5-HT2A, in the order of strength of inhibition. GlyT2 is a sodium- and chloride-dependent transporter that recycles Gly from the synaptic cleft into the presynaptic Gly terminals in the spinal cord, brainstem, and cerebellum. Inhibition of GlyT2 allows Gly to remain longer in the synaptic cleft and bind to postsynaptic Gly receptors, thereby enhancing inhibitory neurotransmission and potentially relieving chronic neuropathic pain. P2X3 antagonists are being investigated for refractory chronic cough, overactive bladder, endometriosis, and chronic pain, especially diabetic neuropathic pain. A 5-HT2A antagonist is used to treat psychiatric disorders, cardiovascular disorders, and nausea/vomiting. It also attenuates pain-related behavior and suppresses 5-HT2A expression in the dorsal root ganglion. Based on the triple analgesic mechanisms, opiranserin is mainly suitable for neuropathic pain which can contribute to pain chronification and partially helpful for nociceptive pain. Among the three proposed analgesic targets of opiranserin, published studies have focused on the effects mediated by GlyT2 and 5-HT2A antagonism, whereas the contribution of P2X3 antagonism has not been adequately investigated. Therefore, therapeutic effects and adverse events related to P2X3 cannot be fully anticipated. The major clinical concern is that opiranserin cannot be added to disposable intravenous patient-controlled analgesia devices due to their limited volume. Repeated administration may accumulate its active metabolite, VVZ-368 (N-desmethyl-VVZ-149).

The widespread presence of microplastics in the environment has raised concerns about potential health effects following oral exposure in humans, particularly in individuals with impaired intestinal barrier function. This study investigated the effects of dietary polyvinyl chloride (PVC) microplastics fragments (< 25 μm) in healthy and dextran sodium sulfate (DSS)-induced colitis Wistar rats, with a complementary assessment in a human 3D intestinal microtissue model. Rats received control feed or feed supplemented with 0.1% (w/w) PVC for three weeks, with or without 3 % DSS administration during the first week to induce mild colitis. Intestinal permeability was evaluated using a FITC-dextran assay, tight junctions' proteins were investigated by Western blot, histopathology was assessed in colon sections, and transcriptomic changes were analysed in jejunum and colon tissue by RNA sequencing followed by pathway enrichment analysis. In parallel, human EpiIntestinal FT microtissues were exposed to PVC and/or DSS to assess viability, barrier integrity, and tissue morphology. PVC exposure was well tolerated and did not affect weight gain or overall well-being of the animals. Intestinal permeability increased in female rats exposed to PVC or DSS alone, whereas no significant changes were observed in males. Histological alterations were subtle and mainly focal. Transcriptomic analyses revealed pronounced sex- and tissue-specific responses, with stronger effects in females, particularly in the colon and under inflammatory conditions. Altered genes and enriched pathways were primarily related to apoptosis, lipid metabolism, immune and inflammatory signalling, energy homeostasis, and hormone signalling, including PPAR-associated pathways. Male rats showed fewer and less consistent transcriptional changes. No adverse effects were observed in the human intestinal model, suggesting limited acute toxicity. Overall, short-term oral PVC exposure induced modest but distinct sex-dependent molecular responses, highlighting the importance of considering sex and pre-existing inflammatory status when assessing microplastic toxicity.

Eggshell membrane is an abundant agricultural by-product from the egg-processing industry, most of which is landfilled and thus deprived of high-value valorization. Herein, a mild one-step alkaline procedure was developed to simultaneously extract keratin and gelatin from waste eggshell membrane. Composite protein coacervates were prepared by adjusting pH, sodium chloride concentration and gelatin-to-keratin mass ratio. Their phase behavior, microstructure, molecular interactions and functional properties were characterized to elucidate protein synergistic mechanisms. Quantitative experiments determined the optimal conditions: pH 4.5, 50 mmol/L NaCl, and a gelatin/keratin mass ratio of 8:2. Electrostatic interactions triggered coacervation, while hydrogen bonds, hydrophobic forces and thiol interactions stabilized the network alongside protein conformational transitions and disulfide-bond rearrangement. The optimized 8:2 coacervate showed a compact microstructure, improved rheological and emulsifying performance, and 23.4% free-radical-scavenging activity. This facile green strategy achieves full-value recovery of egg-processing waste and promotes sustainable valorisation of agricultural by-products.

Alzheimer's disease (AD), a progressive neurodegenerative disorder, characterized by the deposition of amyloid-β plaques in the hippocampus, leading to cognitive and behavioral impairments. This study investigated the neuroprotective outcome of Dapagliflozin (DAPA), a sodium-glucose cotransporter 2 inhibitor primarily used for glycemic control, which also exhibits notable anti-inflammatory, antioxidant, and neuroprotective properties. Using an aluminum chloride (AlCl3)-induced rat model of AD, the research evaluates behavioral, biochemical, and neuroinflammatory changes, particularly focusing on the nuclear factor kappa-B protein (NF-κB) signaling pathway. Rats were orally administered AlCl3 to induce AD-like pathology, followed by DAPA treatment (1 and 2 mg/kg, p.o.) over a 28-day period. Behavioral assessments, including the Morris water maze and Elevated Plus Maze, were used to evaluate spatial memory and anxiety. On day 29, hippocampal tissues were collected to assess neurotransmitter levels, oxidative stress markers (LPO, GSH, nitrite), and inflammatory cytokines (interleukin-1 beta, interleukin-6), along with the expression of NF-κB. AlCl3 exposure led to significant alterations in neurotransmitter balance (AChE, GABA, and glutamate), heightened oxidative stress, and increased neuroinflammatory responses. DAPA treatment significantly mitigated these changes, notably downregulating NF-κB, which correlated with decreased amyloid beta and expression in the hippocampus. These findings suggest that beyond its antidiabetic action, DAPA offers promising neuroprotection against AlCl3-induced neurotoxicity, potentially via modulation of the NF-κB signaling pathway.