Search Results (491)

Prostate stem cell antigen (PSCA) is a Ly6/uPAR protein that targets neuronal nicotinic acetylcholine receptors (nAChRs). It exists in membrane-tethered and soluble forms, with the latter upregulated in Alzheimer’s disease. We hypothesize that PSCA may be linked to a wider spectrum of neurological diseases and could induce neuroinflammation. Indeed, PSCA expression is significantly upregulated in the brain of patients with multiple sclerosis, Huntington’s disease, Down syndrome, bipolar disorder, and HIV-associated dementia. To investigate PSCA’s structure, pharmacology, and inflammatory function, we produced a correctly folded water-soluble recombinant analog (ws-PSCA). In primary hippocampal neurons and astrocytes, ws-PSCA differently regulates secretion of inflammatory factors and adhesion molecules and induces pro-inflammatory responses by increasing TNFβ secretion. Heteronuclear NMR and ¹⁵N relaxation measurements reveal a classical β-structural three-finger fold with conformationally disordered loops II and III. Positive charge clustering on the molecular surface suggests the functional importance of ionic interactions by these loops. Electrophysiological studies in Xenopus oocytes point on ws-PSCA inhibition of α3β2-, high-, and low-sensitive variants of α4β2- (IC₅₀ ~50, 27, and 15 μM, respectively) but not α4β4-nAChRs, suggesting targeting of the β2 subunit. Ensemble docking and molecular dynamics simulations predict PSCA binding to high-sensitive α4β2-nAChR at α4/β2 and β2/β2 interfaces. Complexes are stabilized by ionic and hydrogen bonds between PSCA’s loops II and III and the primary and complementary receptor subunits, including glycosyl groups. This study gives new structural and functional insights into PSCA’s interaction with molecular targets and provides clues to understand its role in the brain function and mental disorders. Full article

Background/Objectives: Glutamatergic neurotransmission is essential for the normal functioning of the retina. Photoreceptor to bipolar and bipolar to ganglion cell signaling is mediated by L-glutamate, which is stored in and released from vesicular glutamate transporter 1 (VGLUT1) containing synaptic vesicles. VGLUT1 is expressed postnatally, P2 onwards, and is required for the glutamatergic retinal wave observed between P10 and P12 in the developing mouse retina. P9–P13 postnatal age is critical for retinal development as VGLUT1 expressing ribbon synapses activate in the outer and inner plexiform layers, and rod/cone mediated visual signaling commences in that period. Although it has been hypothesized that glutamatergic extrinsic signaling drives cell cycle exit and initiates cellular differentiation in the developing retina, it is not clear whether intracellular, synaptic, or extrasynaptic vesicular glutamate release contributes to this process. Recent studies have attempted to decipher VGLUT’s role in retinal development. Here, we investigate the potential effect of genetic loss of VGLUT1 on early postnatal histogenesis and development of retinal neural circuitry. Methods: We employed immunohistochemistry and electrophysiology to ascertain the density of glutamatergic, cholinergic, and dopaminergic cells, spontaneous retinal activity, and light responses in VGLUT1 null retina, and contrasted them with wildtype (WT) and melanopsin null retina. Results: We have demonstrated here that VGLUT1 null retina shows signs of age dependent retinal degeneration, similar to other transgenic mice models with dysfunctional photoreceptor to bipolar cell synapses. The loss of VGLUT1 specifically alters glutamatergic cell density and morphological maturation of retinal ganglion cells. Moreover, VGLUT2 expression is lost in the majority of VGLUT2 cones in the absence of VGLUT1 coexpression, except when VGLUT2 coexpresses transiently with VGLUT3 in these cones, or when VGLUT1 null mice are dark reared. Conclusions: We present the first evidence that synaptic or extrasynaptic postnatal glutamate release from VGLUT1 containing vesicles impacts histogenesis of glutamatergic cells, pruning of retinal ganglion cell dendrites and VGLUT2 expression in cones. Full article

Maternal Immune Activation (MIA) is a phenomenon of pathophysiological stimulation of the maternal immune system during gestation which potentially leads to functional and structural disturbances of fetal neurogenesis. It occurs due to the alteration of paracrine signals between the maternal organism and the developing nervous system of the fetus. Any disturbances in the brain at embryonic and early postnatal stages might compromise its natural developmental trajectory, which could potentially increase the risk of developing neuropsychiatric disorders, such as schizophrenia, autistic spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), major depressive and bipolar disorders, etc. Presumably, all these conditions could initiate the development of age-related cognitive impairment in late ontogenesis, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and others. As the main immune cell population in the CNS, microglia both mediate its proper development and receive pathological stimuli from the maternal organism. This could lead to microglia premature activation and could become a part of the mechanisms of the fetal CNS development alterations. In this review, we discuss the role of prenatal activation of microglia in neuropsychiatric disorders and neurodegenerative disease development. We highlight approaches to modeling MIA, as well as sex differences in the morphological and functional state of microglia in the context of physiological conditions. There is a hypothesis discussed regarding the contribution of these distinctions to neuropsychiatric disorders and neurodegenerative disease incidence, prevalence, and progression in males and females. Full article

Due to the exceptional corrosion resistance, chemical stability, and dense microstructure, carbon-based thin films are extensively employed in hydrogen energy systems. This study employed magnetron sputtering to fabricate amorphous carbon (a-C) films on SS316L substrates, aiming to improve the corrosion resistance of bipolar plates (BPs) in proton exchange membrane fuel cells (PEMFCs). Using a Taguchi design, the effects of working pressure, sputtering power, substrate bias, and deposition time on film properties were systematically examined and optimized. Films were examined via field emission scanning electron microscopy (FE-SEM), contact angle measurements, and electrochemical tests. Comprehensive evaluation by the Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) method identified optimal conditions of 1.5 Pa pressure, 150 W radio frequency (RF) power, −250 V bias voltage, and 60 min deposition, yielding dense, uniform films with a corrosion current density of 1.61 × 10⁻⁶ A·cm⁻² and a contact angle of 106.36°, indicative of lotus leaf-like hydrophobicity. This work enriches the theoretical understanding of a-C film process optimization, offering a practical approach for modifying fuel cell bipolar plates to support hydrogen energy applications. Full article

Over the past two decades, several add-on modules for computational fluid dynamics (CFD) software focusing on modelling electrochemical processes and two-phase effects within fuel cells have been described in the literature. Most of these models are based on custom-written code that is not openly accessible to everyone. Furthermore, several commercial CFD codes offer specific modules for modelling fuel cells. Here, code modification is difficult to achieve. This work analyses and further develops the PEMFC toolbox of Kone et al. for use in OpenFOAM to simulate low temperature (LT-)PEM fuel cells. This model is freely available under the GNU GPLv3 licence. The present work focuses on enhanced physical and electrochemical modelling and improved user-friendliness. The major improvements compared to the original toolbox will be detailed in the article, together with the first results obtained. The improved PEMFC toolbox is validated using experimental data from an automotive fuel cell stack design. Furthermore, these results are compared to the original Kone model, and a commercially available CFD model. The improved toolbox reproduces both the experimentally measured polarisation curve and the current density distribution quite accurately, producing results that are fairly comparable to the more sophisticated commercial model. Full article

NiTi alloy has emerged as a promising bipolar plate (BP) material for proton exchange membrane fuel cells (PEMFCs), combining Ti-like corrosion resistance with Ni-like electrical conductivity through its intermetallic characteristics. However, its performance faces greater challenges under aggressive operating conditions (70 °C, F⁻-containing acidic solution with air bubbling). This study demonstrates that Nb alloying effectively enhances NiTi while preserving its balanced properties. The developed NiTiNb alloy exhibits improved performance with 26% lower corrosion current density (i_c) and 29% reduced interfacial contact resistance (ICR) compared to conventional NiTi, effectively overcoming the conventional corrosion–conductivity trade-off in metallic BPs. The alloy also shows superior electrochemical stability and microhardness relative to pure Ti and Ni. These enhancements stem from a unique dual-phase microstructure comprising a NiTi (B2) matrix with continuous β-Nb grain boundary networks. During operation, this structure enables in situ formation of protective TiO₂-Nb₂O₅ films while maintaining conductive Nb/Nb₂O₅ pathways and metallic Ni domains. The findings establish Nb alloying as a viable optimization strategy for NiTi-based BP substrate in demanding PEMFC applications. Full article

Metal nitride coatings have been considered as a promising approach to improve the performance of metal bipolar plates for proton exchange membrane fuel cells (PEMFCs). In this study, NbN_x coatings with three different ratios of N₂/Ar (1:2, 1:1 and 3:1) were prepared on TC4 alloy substrates using the double glow plasma alloying technology. The NbN_x coatings are homogeneous and dense, and the phase of the coating transforms from hexagonal β-Nb₂N to δ′-NbN phase as the nitrogen content increases. All coatings demonstrate high protective efficiency, with the coating (N₂/Ar ratio of 3:1) displaying the lowest current density of 8.92 × 10⁻⁶ A/cm² at a working voltage of 0.6 V. The EIS results also show that this coating has the best corrosion resistance. Notably, it also presents the lowest interfacial contact resistance of 7.29 mΩ·cm² at 1.5 MPa and good hydrophobicity. More importantly, this study provides a new idea and method for corrosion-resistant coatings of metal bipolar plates for PEMFC applications. Full article

The geometric design of flow channels in bipolar plates is one of the critical features of proton exchange membrane fuel cells (PEMFCs), as it determines the power output of the fuel cell and has a significant impact on its performance and durability. The function of the bipolar plate is to guide the transfer of reactant gases to the gas diffusion layer and catalytic layer inside the PEMFC, while removing unreacted gases and gas–liquid byproducts. Therefore, the design of the bipolar plate flow channel is directly related to the water and thermal management of the PEMFC. In order to improve the comprehensive performance of PEMFCs and ensure their safe and stable operation, it is necessary to design the flow channels in bipolar plates rationally and effectively. This study addresses the limitations of existing bipolar plate flow channels by proposing a new coupling of serpentine and radial channels. The distribution of oxygen, water concentrations, and temperature inside the channel is simulated using the multi-physics simulation software COMSOL Multiphysics 6.0. The performance of this novel design is compared with conventional flow channels, with a particular focus on the pressure drop and current density to evaluate changes in the output performance of the PEMFC. The results show that the maximum current density of this novel design is increased by 67.36% and 10.43% compared to straight channel and single serpentine channels, respectively. The main contribution of this research is the innovative design of a new coupling of serpentine and radial channels in bipolar plates, which improves the overall performance of the PEMFC. This study provides theoretical support for the design of bipolar plate flow channels in PEMFCs and holds significant importance for the green development of energy. Full article

High-frequency (h. f.) harmonic distortion (HD) of advanced SiGe heterojunction bipolar transistor (HBT)-based power cells (PwCs), featuring optimized metallization interconnections between individual HBTs, was investigated. Single tone input power (P_in) excitations at 1, 2, 5, and 10 GHz frequencies were employed. The output power (P_out) of the fundamental tone and its harmonics were analyzed in both the frequency and time domains. A rapid increase in the third harmonic of P_out was observed at input powers exceeding −8 dBm for a fundamental frequency of 10 GHz in two different PwC technologies. This increase in the third harmonic was analyzed in terms of nonlinear current waveforms, the nonlinearity of the HBT p-n junction diffusion capacitances, substrate current behavior versus P_in, and avalanche multiplication current. To assess the RF power performance of the PwCs, scalar and vectorial load-pull (LP) measurements were conducted and analyzed. Under matched conditions, the SiGe PwCs demonstrated good linearity, particularly at high frequencies. The key power performance of the PwCs was measured and simulated as follows: input power 1 dB compression point (P_{in_1dB}) of −3 dBm, transducer power gain (G_T) of 15 dB, and power added efficiency (PAE) of 50% at 30 GHz. All measured data were corroborated with simulations using the compact model HiCuM L2. Full article

Calcium channel blockers (CCBs), originally developed for cardiovascular indications, have gained attention for their therapeutic potential in neuropsychiatric, endocrine, and pain-related disorders. In neuropsychiatry, nimodipine and isradipine, both L-type CCBs, show mood-stabilizing and neuroprotective effects, with possible benefits in depression, bipolar disorder, and schizophrenia. In endocrinology, verapamil, a non-dihydropyridine L-type blocker, has been associated with the preservation of pancreatic β-cell function and reduced insulin dependence in diabetes. CCBs may also aid in managing primary aldosteronism and pheochromocytoma, particularly in patients with calcium signaling mutations. In pain medicine, α2δ ligands and selective blockers of N-type and T-type channels demonstrate efficacy in neuropathic and inflammatory pain. However, their broader use is limited by challenges in central nervous system (CNS) penetration, off-target effects, and heterogeneous trial outcomes. Future research should focus on pharmacogenetic stratification, novel delivery platforms, and combination strategies to optimize repurposing of CCBs across disciplines. Full article

The vertebrate retina is a complex neural tissue composed of a repeating array of distinct cell types that communicate through specialized synaptic connections. The neurochemistry underlying these connections reveals the synaptic chemistry, including the neurotransmitters involved and their corresponding receptors. The basic pattern of communication is that the pathway from photoreceptors to bipolar cells to ganglion cells typically uses glutamate as the signaling transmitter, with three ionotropic and one metabotropic receptor types. In contrast, much of the lateral feedback, performed by horizontal cells and amacrine cells, uses the inhibitory neurotransmitter GABA, while other amacrine cells use glycine or dopamine. This review examines all of these neurotransmitter systems for each retinal cell type, along with how these systems process the visual signals transmitted to the lateral geniculate nucleus and the visual cortex. Full article

The efficacy of in vitro fertilization (IVF) is significantly hindered by early embryonic developmental failure and oocyte maturation arrest. Recent findings in reproductive genetics have identified several oocyte-specific genes—TUBB8, KIF11, and CKAP5—as essential regulators of meiotic spindle formation and cytoskeletal dynamics. Mutations in these genes can lead to significant meiotic defects, fertilization failure, and embryo arrest. The links between genotype and phenotype, along with the underlying biological mechanisms, remain inadequately characterized despite the increasing number of identified variations. This systematic review was conducted in accordance with PRISMA 2020 guidelines. Relevant papers were retrieved from the PubMed and Embase databases using combinations of the keywords “TUBB8,” “KIF11,” “CKAP5,” “oocyte maturation arrest,” “embryonic arrest,” and “IVF failure.” Studies were included if they contained clinical, genomic, and functional data on TUBB8, KIF11, or CKAP5 mutations in women undergoing IVF. Molecular data, including gene variant classifications, inheritance models, in vitro tests (such as microtubule network analysis in HeLa cells), and assisted reproductive technology (ART) outcomes, were obtained. Eighteen trials including 35 women with primary infertility were included. Over fifty different variants were identified, the majority of which can be attributed to TUBB8 mutations. TUBB8 disrupted α/β-tubulin heterodimer assembly due to homozygous missense mutations, hence hindering meiotic spindle formation and leading to early embryo fragmentation or the creation of many pronuclei and cleavage failure. KIF11 mutations resulted in spindle disorganization and chromosomal misalignment via disrupting tubulin acetylation and microtubule transport. Mutations in CKAP5 impaired bipolar spindle assembly and microtubule stabilization. In vitro validation studies showed cytoskeletal disturbances, protein instability, and dominant negative effects in transfected animals. Donor egg IVF was the sole effective treatment; however, no viable pregnancies were documented in patients with pathogenic mutations of TUBB8 or KIF11. TUBB8, KIF11, and CKAP5 are essential for safeguarding oocyte meiotic competence and early embryonic development at the molecular level. Genetic differences in these genes disrupt microtubule dynamics and spindle assembly, resulting in various aspects of oocyte maturation and fertilization. Functional validation underscores the necessity of routine genetic screening for women experiencing unresolved IVF failure, as it substantiates their causal role in infertility. Future therapeutic avenues in ART may be enhanced by tailored counseling and innovative rescue methodologies like as gene therapy. Full article

Posterior pituitary tumors (PPTs) are rare, non-neuroendocrine neoplasms derived from pituicytes of the neurohypophysis or infundibulum. According to the 2025 WHO classification, PPTs comprise four distinct but related low-grade entities: pituicytoma, granular cell tumor of the sellar region, spindle cell oncocytoma, and ependymal pituicytoma. All share nuclear TTF-1 expression, confirming their common origin, but differ in morphology, immunophenotype, and ultrastructure. Histologically, pituicytomas consist of bipolar spindle cells in fascicles; granular cell tumors show polygonal cells with PAS-positive, diastase-resistant cytoplasmic granules; spindle cell oncocytomas display oncocytic change and abundant mitochondria; and ependymal pituicytomas exhibit perivascular pseudorosettes and EMA positivity in apical or dot-like patterns. Immunohistochemically, all are S100 and vimentin positive, and negative for pituitary hormones and lineage-specific transcription factors. Clinically, PPTs are typically non-functioning but may be associated with corticotroph or somatotroph hyperfunction. Imaging features are nonspecific. Surgical resection is the treatment of choice, although hypervascularity and adherence—especially in spindle cell oncocytomas—can hinder complete excision. Radiotherapy is reserved for recurrences. Molecular analyses reveal recurrent alterations in MAPK/PI3K pathways (e.g., HRAS, BRAF, FGFR1, NF1, TSC1) and suggest a shared histogenesis. Copy number imbalances correlate with reduced progression-free survival in some subtypes. Despite a generally favorable prognosis, recurrence—particularly in spindle cell oncocytomas—necessitates long-term follow-up. The WHO 2025 update provides a unified framework for classification, diagnosis, and prognostic stratification of these rare tumors. Full article

High-temperature fuel cells and electrolyzers, particularly molten carbonate fuel cells (MCFCs) and Molten Carbonate Electrolyzers (MCEs), are expected to play a critical role in clean power generation, hydrogen production, and integrated CO₂ separation. Unfortunately, despite their potential, these technologies have not yet reached full commercialization. The main reason for this is material degradation. In particular, the corrosion of metallic components continues to be a leading cause of performance loss and system failure. This review provides a comprehensive assessment of degradation mechanisms in MCFC and MCE systems. It examines key metallic components, such as current collectors and bipolar plates, focusing on the performance of commonly used materials, including stainless steels and advanced alloys, under prolonged exposure to corrosive environments. To address degradation issues, this review evaluates current mitigation strategies and discusses material selection, protective coatings application, and the optimization of operational parameters. Advances in alloy development, coatings, surface treatments, and process controls have been compared in terms of effectiveness, scalability, and long-term stability. The review concludes with a synthesis of current best practices and future directions, emphasizing the need for integrated, multi-functional solutions to achieve the lifetimes required for full commercialization. By linking materials science, electrochemistry, and systems engineering, this review offers directions for the development of corrosion-resistant MCFC and MCE technologies in support of a hydrogen-based, carbon-neutral energy future. Full article

Ti/a-C:Cr multilayer films were deposited on 316L stainless steel (SS316L) substrates using medium-frequency alternating current magnetron sputtering, with a single-layer a-C:Cr film also prepared on a titanium substrate. The influence of sputtering pressure on the film’s structure and properties was systematically investigated. Film morphology and microstructure were analyzed via X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and atomic force microscopy (AFM). At a pressure of 1.4 MPa, the interfacial contact resistance (ICR) of SS316L bipolar plates (BPPs) coated with the films reached as low as 3.30 mΩ·cm², while that of titanium BPPs was 2.90 mΩ·cm². Under simulated proton exchange membrane fuel cell (PEMFC) cathode conditions (70 °C, 0.6 V vs. SCE, 0.5 M H₂SO₄, 5 ppm HF solution), the corrosion current density, Icorr, reached optimal values of 0.69 μA·cm⁻² for SS316L and 0.62 μA·cm⁻² for titanium. These results demonstrate that parameter optimization enables SS316L BPPs to functionally replace titanium counterparts, offering significant cost reductions for metal BPPs and accelerating the commercialization of PEMFC technology. Full article