Search Results (32,224)

The translocator protein (TSPO), an evolutionarily conserved protein located on the outer mitochondrial membrane, is typically expressed at low levels in the central nervous system under normal physiological conditions. However, its expression can increase in response to various pathological conditions, such as neurodegenerative diseases and neuroinflammation. Retinitis pigmentosa (RP) refers to a group of inherited degenerative diseases of the retina; the progression of the pathology is linked to a chronic inflammatory state that leads to the progressive loss of photoreceptors and ultimately to blindness. One of the key processes contributing to the gradual loss of photoreceptors is neuroinflammation, a mechanism in which the TSPO plays a newly studied role. In this context, TSPO could be an excellent target. In the current study, rd10 mice of both sexes were treated with a TSPO ligand, PIGA1138, as an ophthalmic suspension (1 mg/mL) from post-natal day (P)18 to P30, P60, and P90. Retinal function was evaluated through electroretinography, while visual acuity was assessed using the Prusky Water Maze task. Additionally, molecular analyses were performed to assess TSPO expression, alongside examinations of retinal morphology. Results showed significant retinal preservation, reduced photoreceptor loss, and improved retinal responses, suggesting preserved visual function. These findings highlight PIGA1138’s potential in mitigating retinal degeneration and preserving function in retinal diseases like RP. Full article

Sarcodon aspratus fruiting polysaccharides (SAFP) exhibit multiple therapeutic properties. In this study, a type 2 diabetes mellitus (T2DM) mouse model was established using a high-fat diet (HFD) and streptozotocin to evaluate the antidiabetic potential of SAFP. Then the benefits of SAFP on glucolipid metabolism, gut barrier integrity and intestinal microbiota were evaluated. The results indicated that SAFP alleviated disturbances in glycolipid metabolism and insulin resistance through activating Adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway. Furthermore, SAFP ameliorated hepatic inflammation and hepatic steatosis, as well as restored dysbiosis in hepatic function. Notably, SAFP enhanced intestinal mucosal architecture and strengthened epithelial barrier functionality through upregulated expression of tight junction components such as Zonula occludens-1(ZO-1), Claudin-1, and Occludin proteins. The 16S rRNA analysis indicated that SAFP has the potential to restore the intestinal microbial barrier in T2DM mice through elevation of short-chain fatty acids (SCFAs) concentrations and regulation of microbial community imbalances. This research offers foundational evidence supporting the utilization of SAFP as an innovative dietary supplement or prospective prebiotic component in functional food formulations targeting diabetes management. Full article

Climate change and socio-economic transformation increasingly challenge the stability of China’s food supply. This study aims to optimize grain crop layouts by integrating natural suitability and nutritional supply within a unified analytical framework. Using the MaxEnt model incorporating bioclimatic, topographic, and soil variables, we simulated the natural suitability of major grain crops and compared it with actual planting patterns based on the SPAM dataset. Results revealed substantial spatial discrepancies between actual and suitable distributions, with national planting diversity index increasing by 26.42% (from 0.53 to 0.67) under suitable conditions. Wheat and maize are most suited to northern China, rice and tuber crops to southern regions, while soybean performs optimally in the northeast. Nutrient supply potential also improved substantially under the suitable scenario, with energy, protein, fat, and carbohydrate increasing by 56.9 × 10⁸ KJ, 77.2 × 10⁶ g, 23.3 × 10⁶ g, and 48.6 × 10⁶ g per million people, respectively. Among alternative structures, maize-soybean and maize-based planting structures better aligned with both natural adaptability and nutritional balance (e.g., in Inner Mongolia and Heilongjiang), whereas rice-based structure showed weaker correspondence (e.g., in Shanghai). These findings demonstrate that naturally adaptive optimization can enhance both environmental compatibility and nutritional adequacy, providing scientific guidance for developing climate-resilient and nutrition-oriented crop layout strategies in China. Full article

H9N2 avian influenza virus (AIV) is widely prevalent in poultry in China. To understand the genetic characteristics and evolution of H9N2 AIVs in Guangxi, southern China, the complete genomes of H9N2 AIVs from 1999–2023 were systematically analysed. Maximum likelihood (ML) trees indicated that H9N2 AIV gene sublineage diversity contributed to genotype diversity, yielding 17 genotypes (G1–G17). Since 2010, genotype G14 (also known as genotype S or G57) has become predominant in poultry in Guangxi. Phylogenetic analysis in the HA has resulted in the distancing of recent Guangxi isolates from the vaccine strains. This study also revealed that the genotypes of H9N2 AIVs infecting swine, equines and canines in Guangxi were consistent with those found in avian species at the same time, highlighting the capacity of H9N2 AIVs to be transmitted across species. The antigenic residues in the HA head region and NA protein of the Guangxi isolates from 2020–2023 changed significantly compared to the vaccine strains, suggesting possible antigenic drift in these viruses. Amino acid analysis of the HA protein revealed that 84.9% (73/86) of H9N2 AIV isolates from Guangxi, including those from live poultry markets, preferentially bound to α-2,6 sialic acid receptors. Considerable attention should be given to cross-species transmission of H9N2 AIV in the region. On the basis of these findings, strengthening the monitoring of H9N2 AIV in poultry in Guangxi is essential. Full article

Background/Objectives: In the present study, the Metabolic dysfunction-associated fatty liver disease (MAFLD) and Metabolic dysfunction-associated steatotic liver disease (MASLD) diagnostic criteria were applied to evaluate the relative performance in predicting short-term advanced fibrosis (AF) progression (AFpr) and hepatocellular carcinoma (HCC), as well as an ancillary outcome, i.e., the occurrence of acute cardiovascular events (ACEs) in steatotic liver disease (SLD) patients. Methods: We retrospectively analyzed the data stored in the University Hospital (UH)’s Official Health Documents Digitization Archive of 931 SLD patients, with a follow-up of 3 years. Based on the Body Mass Index (BMI), patients were subdivided into lean “L” (BMI < 25 kg/m²) (n = 134) and not-lean “NL” (n = 797), and, subsequently, into NL-MASLD (n = 206), NL-MASLD/MAFLD (n = 481), NL-MAFLD (n = 110), L-MASLD (n = 39), L-MASLD/MAFLD (n = 68), and L-MAFLD (n = 27). All study outcomes (AFpr, HCC, and ACE) were primarily evaluated in NL-SLD and by conducting a sub-analysis of L-SLD individuals. Results: MASLD and MAFLD criteria similarly estimated [p = 0.076] the overall 3-year risk of AF progression in NL-SLD. In the L-SLD sub-analysis, MAFLD criteria better estimated the overall 3-year risk of AF progression [p = 0.006]. Multivariate competing risk analysis (adjusted for sex, age, diabetes, steatosis, and fibrosis severity) revealed diabetes [adjusted Hazard Ratio (aHR) = 2.113, p = 0.001], high-sensitivity C-reactive protein (aHR = 1.441; p = 0.02), and Homeostatic Model Assessment for Insulin Resistance (aHR = 1.228; p = 0.03) as being associated with AF progression in L-MAFLD. Compared to MAFLD, MASLD diagnostic criteria similarly estimated the 3-year risk of HCC occurrence both in NL [HR = 1.104, C.I. 95%: 0.824–1.593, p = 0.741] and L [HR = 1.260, C.I. 95%: 0.768–2.104, p = 0.701] patients. Finally, no significant differences were reported between the MAFLD or MASLD criteria for ACE risk occurrence in all study groups. Conclusions: The MAFLD criteria better estimate the AF progression risk, limited to L-SLD patients. Full article

Voltage-sensing phosphatases (VSPs) provide a conserved framework for dissecting the mechanics of voltage sensing and for engineering genetically encoded voltage indicators (GEVIs). To evaluate how natural sequence diversity shapes function, we compared VSP voltage-sensing domains (VSDs) from multiple species by replacing the phosphatase domain with a fluorescent protein to enable optical detection of VSD responses. Every construct that reached the plasma membrane produced a voltage-dependent optical signal, underscoring the deep conservation of voltage sensing across VSP orthologs. Yet lineage-specific substitutions generated strikingly different phenotypes. A plankton VSP ortholog from Eurytemora carolleeae and the Sea Hare (Aplysia californica) VSP exhibited left-shifted activation ranges, producing robust fluorescence transitions during modest depolarizations of the plasma membrane. The human VSD of hVSP2 yielded weak, sluggish responses with poor recovery, but reintroduction of a conserved arginine in S1 (G95R) partially restored reversibility, implicating lipid-facing residues in conformational stability. The Chinese hamster (Cricetulus griseus) VSD, with atypical S4 sensing charges (RWIR), generated a slow fluorescence increase during depolarization, while reverting to the consensus arginine (RRIR) inverted the polarity to a decrease. These contrasting behaviors show that single residue changes can reshape how VSD movements influence the fluorescent reporter, highlighting the molecular precision revealed by GEVI measurements. Together, these results show that voltage-dependent signaling is deeply conserved across VSPs but shaped by lineage-specific sequence variation, establishing VSPs as powerful models for probing voltage sensing and guiding GEVI design. Full article

Background: Neurological disorders are the leading cause of disability, affecting over three billion people worldwide. Amyotrophic lateral sclerosis (ALS) is among the most feared and uniformly fatal neurodegenerative diseases, with no therapy capable of restoring lost function. Methods: We report the first application of therapeutic fever to ALS using Computerized Brain-Guided Intelligent Thermofebrile Therapy (CBIT²). This fully noninvasive treatment, delivered through an FDA-approved computerized platform, digitally reengineers the 1927 Nobel Prize-recognized malarial fever therapy into a modern treatment guided by the Brain–Eyelid Thermoregulatory Tunnel. CBIT² induces therapeutic fever through synchronized hypothalamic feedback, activating heat shock proteins, which are known to restore proteostasis and neuronal function. Case presentation: A 56-year-old woman was diagnosed with progressive ALS at the Mayo Clinic, with electromyography (EMG) demonstrating fibrillation and fasciculation indicative of denervation corroborated by neurological and MRI findings; the patient was informed that she had an expected survival of three to five years. A neurologist from Northwestern University confirmed the diagnosis and thus maintained the patient on FDA-approved ALS drugs (riluzole and edaravone). Her condition rapidly worsened despite pharmacological treatment, and she underwent CBIT², resulting in (i) electrophysiological reversal with complete disappearance of denervation; (ii) biomarker correction, including reductions in neurofilament and homocysteine, IL-10 normalization (previously linked to mortality), and robust HSP70 induction; (iii) restoration of gait, swallowing, respiration, speech, and cognition; (iv) reconstitution of tongue structure; and (v) return to complex motor tasks, including golf, pickleball, and swimming. Discussion: This case provides the first documented evidence that ALS can be reversed through digitally reengineered fever therapy aligned with thermoregulation, which induces heat shock response and upregulates heat shock proteins, resulting in the patient no longer meeting diagnostic criteria for ALS and discontinuation of ALS-specific medications. Beyond ALS, shared protein-misfolding pathology suggests that CBIT² may extend to Alzheimer’s, Parkinson’s, and related disorders. By modernizing this Nobel Prize-recognized therapeutic principle with computerized precision, CBIT² establishes a framework for large-scale clinical trials. A century after fever therapy restored lost brain function and so decisively reversed dementia paralytica such that it earned the 1927 Nobel Prize in Medicine, CBIT² now safely harnesses the therapeutic power of fever through noninvasive, intelligent, brain-guided thermal modulation. Amid a global brain health crisis, fever-based therapies may offer a path to preserve thought, memory, movement, and independence for the more than one-third of humanity currently affected by neurological disorders. Full article

Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular disorder with high mortality and long-term disability. It is more prevalent in women than men, but most preclinical research has been performed in male animals. Upregulation of lipocalin-2 (Lcn2), an acute-phase protein involved in iron homeostasis and neuroinflammation, has been implicated in hemorrhagic brain injury in male animals. The purpose of this study was to examine whether genetic deletion of Lcn2 also reduces early brain injury after SAH in female mice. Adult female wild-type (WT) and Lcn2 knockout (KO) mice were subjected to endovascular perforation to induce SAH. Lcn2 expression was assessed by immunohistochemistry and Western blotting, while brain injury was evaluated using MRI T2 lesion measurement, blood–brain barrier (BBB) permeability assays, Fluoro-Jade C staining, and Garcia’s neurological scoring. We found that Lcn2 expression was upregulated in multiple brain regions after SAH, particularly in astrocytes. Compared with WT mice, Lcn2 KO mice exhibited significantly reduced oxidative stress, attenuated ferritin induction, smaller T2 lesions, decreased BBB leakage, reduced neuronal degeneration, and improved neurological recovery over 7 days. These findings identify Lcn2 as a critical mediator of early brain injury after SAH in female mice. These results further support targeting Lcn2 as a therapeutic strategy to reduce brain damage and improve outcomes in SAH patients. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, amyloid-β (Aβ) pathology, synaptic degeneration, impaired neurogenesis, and chronic neuroinflammation. KBN2202, a small-molecule salicylic acid derivative [2-[(2-naphthalen-1-yloxy)ethyl]amino]-4-hydroxybenzoic acid], was investigated for its potential as a multi-target therapeutic agent in advanced-stage AD. To this end, 9-month-old 5xFAD mice with established AD-like pathology received daily oral KBN2202 (5 or 20 mg/kg) or vehicle for 12 weeks. KBN2202 demonstrated broad histopathological benefits. It preserved hippocampal CA1 cytoarchitecture and increased dendritic length in cortical neurons. Neurogenic activity was also enhanced, with elevated doublecortin (DCX) expression in the subventricular zone (SVZ). At the molecular level, KBN2202 reduced amyloid precursor protein C-terminal fragments (APP-CTFs), key intermediates in amyloidogenic processing, and histological staining confirmed a significant reduction in fibrillar and diffuse Aβ plaque burden in the cortex and hippocampus. Furthermore, KBN2202 attenuated astrocytic and microglial activation, indicating suppression of chronic neuroinflammation. In behavioral assessments, KBN2202 significantly improved recognition memory in the novel object recognition (NOR) test, while Y-maze performance remained unchanged. Overall, the compound exhibited robust neuroprotective, pro-neurogenic, anti-amyloid, and anti-inflammatory effects. These findings support the therapeutic potential of KBN2202 as a multi-functional candidate for symptomatic-stage AD. Full article

Fecal sludge (FS) requires effective management to mitigate environmental and public health risks and enable resource recovery. This study evaluated the effects of microwave (MW) treatment on FS characteristics and subsequent anaerobic digestion (AD) performance. MW treatment raised FS temperatures to ~96 °C, reducing FS volume by 50% and inducing three thermal phases. Soluble chemical oxygen demand (sCOD) showed a multi-phase pattern, with a maximum solubilization of 29.8% during initial heating due to the solubilization of proteins and carbohydrates. Scanning electron microscopy (SEM) revealed morphological changes, while Fourier transform infrared (FTIR) spectroscopy confirmed that core functional groups remained unchanged. MW-pretreated FS enhanced AD performance, achieving a 17% increase in cumulative methane yield, alongside 18% and 33% improvements in organic loading and methane production rates, respectively. MW treatment influenced the phase distribution of digestate components, showing a shift in nutrient portioning towards the liquid fraction. These results suggest that integrating MW pretreatment into FS management systems can improve energy recovery, reduce treatment costs, and support resource-efficient sanitation solutions. Full article

In COVID-19 (coronavirus disease 2019), multi-organ complications depend on the immune system’s activity. α1-Acid glycoprotein (AGP) is a highly glycosylated positive acute-phase protein having multifaceted immunomodulatory and protective effects. We were interested in changes in serum AGP concentrations, expression of its glycans, and oxidation-reduction potential (ORP) between severe COVID-19 patients, convalescents, and healthy controls, and whether any of the analyzed parameters could serve as an additional diagnostic biomarker of severe COVID-19 and/or help monitor recovery. We were also interested in associations between the examined parameters. AGP concentrations were measured using an immunoturbidimetric method. The profile and degree of AGP glycosylation were analyzed using lectin-ELISA with lectins: sialo-specific from Sambucus nigra (SNA) and Maackia amurensis (MAA), fucose-specific from Lotus tetragonolobus (LTA) and Aleuria aurantia (AAL). The static and capacitive ORP (sORP and cORP, respectively) were measured using MiOXSYS C+^® device (Caerus Biotechnologies, Vilnius, Lithuania). Statistica13.3PL software was used for statistical analysis. AGP concentrations increased in COVID-19 patients, showing high clinical usefulness in distinguishing them from convalescents and controls. AGP α2,6-sialylation (reactivity with SNA) was reduced in COVID-19 vs. other study groups, while α2,3-sialylation (reactivity with MAA) was reduced in convalescents vs. controls. The expression of LTA-reactive fucose (Lewis^x structures, Le^x) was reduced in COVID-19 patients compared to controls and convalescents, but AGP reactivity with AAL did not differ between the study groups. The sORP was reduced, and the cORP was increased in COVID-19. The observed negative correlations between sORP and AGP levels may suggest the antioxidant effect of AGP during severe COVID-19. Higher levels of serum AGP in severe COVID-19, together with low expression of sialic acid α2,6-linked and Le^x structures, accompanied by reduced sORP, constitute a characteristic pattern of biomarker expression during severe COVID-19. The increased expression of SNA-reactive sialic acid and Le^x structures may reflect the recovery process after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. The observed negative correlations between AGP and sORP levels may suggest that serum AGP in COVID-19 also plays a role as an antioxidative molecule. Full article

Silage is an essential tool for maintaining productivity, especially during the dry season and when pasture availability is limited. However, it is necessary to establish increasingly efficient methods for producing this feed, seeking to minimize losses and provide maximum nutritional benefit. This study aimed to evaluate the quality of Cenchrus purpureus (Schumach.) Morrone cv. BRS Capiaçu silage with cornmeal addition or after 3 or 5 days of wilting, focusing on fermentative profile, chemical composition, and in situ degradation. A completely randomized design with four treatments and three replicates was used: Control (CON), ensilage with 8% ground cornmeal (SGC), wilting for 3 days (WI3), and wilting for 5 days (WI5), totaling 12 silos. After 120 days, the silages were analyzed for pH, volatile fatty acids, chemical composition, and rumen degradability using three cannulated cows. Data were subjected to ANOVA and Tukey’s test (p < 0.05). The SGC and WI3 treatments showed lower pH (4.55 and 4.52) and butyric acid (0.27 and 0.33%) and higher lactic acid (2.32 and 1.57%) contents compared with CON and WI5 (p < 0.001). They also presented higher dry matter (257.2 and 318.3 g/kg) and crude protein (63.8 and 58.5 g/kg) and lower fiber fractions (p < 0.001). For rumen degradability, SGC had the highest values for fraction “A” and effective degradability of dry matter at 5 and 8%/h passage rates (p = 0.001). Cornmeal addition and 3-day wilting improved silage quality, but only cornmeal enhanced degradability. Full article

Background: Pseudomonas aeruginosa infection is a major driver of morbidity and mortality in cystic fibrosis (CF), yet disease severity varies widely among people with CF (pwCF). This clinical heterogeneity suggests the involvement of host genetic modifiers beyond CFTR. We previously identified sphingosine 1-phosphate receptor 1 (S1PR1) as a candidate gene associated with susceptibility to P. aeruginosa. Here, we investigated its role in modulating airway epithelial responses to infection. Methods: Using CRISPR/Cas9, we generated S1PR1-knockout bronchial epithelial cells with (IB3-1) and without (C38) CFTR mutations. We assessed cell viability, cytotoxicity, and interleukin-8 secretion following exposure to P. aeruginosa exoproducts. S1PR1 protein expression was evaluated in lung tissue from pwCF and non-CF individuals using immunohistochemistry. Results: S1PR1-mutant cells produced truncated, non-functional peptides. In CFTR-mutant cells, S1PR1 loss reduced viability, increased cytotoxicity, and significantly enhanced interleukin-8 production in response to P. aeruginosa exoproducts. These effects were not observed in CFTR-competent cells. Notably, S1PR1 protein levels were markedly lower in lung tissue from pwCF compared to non-CF individuals. Conclusions: S1PR1 deficiency exacerbates epithelial damage and inflammatory responses to P. aeruginosa in CF models. These findings highlight S1PR1 as a potential contributor to infection severity and a promising target for therapeutic strategies in pwCF. Full article

Alzheimer’s disease (AD), epilepsy, and vascular dementia (VaD) are highly prevalent neurological diseases and lead global drivers of morbidity. While these conditions have been historically treated as distinct entities, they now appear to share convergent molecular and cellular processes that drive disease initiation and progression. This narrative review collates evidence from studies published from 2000 to 2025 to investigate overlapping mechanisms and therapeutic opportunities for the three conditions. Five interconnected mechanisms, excitotoxicity, neuroinflammation, oxidative stress, mitochondrial dysfunction, and vascular impairment, were identified as key driving processes resulting in self-sustaining cycles leading to neuronal injury, cognitive impairment, and seizure susceptibility. Clinically, this is represented by shared cognitive, behavioral, and functional impairments, and often, seizures can be overlooked during the dementia process. Therapeutic strategies which may be useful across diseases could include anti-inflammatory treatments, mitochondrial stabilizers, vascular health treatments, and protein aggregation changes. Important translational gaps also exist for practice particularly in the biomarker space and trials that allow intervention across diseases. Each of these conditions, in essence, represent the same inter-relationships at the level of pathophysiology and provides opportunities for multi-targeted treatment approaches and integrated research trajectories to ease the worldwide burden of neurodegenerative disorder. Full article

Background: Periostin can be considered a stimulator of Wnt. Elucidating the relationship between Wnt10a and Periostin in dental pulp stem cells is considered necessary for a deeper understanding of the mechanisms of dental pulp regeneration. Methods: Regenerated dental pulp from ectopic root grafts was double-stained with BrdU and Wnt10a, and the positivity rates were analyzed. Furthermore, the expression levels of Wnt10a, LRP5/6, DKK1, and Periostin within the regenerated tissue were analyzed by PCR. The expression levels of Wnt10a, LRP5/6, DKK1, and Periostin in cells stimulated with Periostin were analyzed by PCR. Wnt10a protein expression was analyzed by Western blotting and ELISA. Similar evaluations were performed with co-stimulation by Periostin and DKK1(Sample size:4). In each experiment, cells not stimulated with periostin served as the control group. Statistical analysis involved confirming the normal distribution of data using QQ plots, followed by one-way analysis of variance and post hoc Turkey’s test. Results: Migrating dental pulp stem cells expressed Wnt10a, and migration was additionally inhibited by its antagonist DKK1. Furthermore, Periostin stimulation increased Wnt10a secretion and suppressed DKK1. Conclusions: Periostin significantly increased Wnt10a expression and DPSC migration, while DKK1 inhibited these effects. Full article