Search Results (2,667)

Cerebral ischemia–reperfusion injury (CIRI) is a complex pathological process that arises when blood flow is restored to the brain after ischemia, often resulting in significant neuronal damage and triggering secondary inflammatory responses. This review explores the immune mechanisms underlying CIRI, focusing on the activation and polarization of resident central nervous system (CNS) cells—particularly microglia and astrocytes—and the infiltration of peripheral immune cells such as neutrophils, monocytes/macrophages, and T lymphocytes. We discuss the central role of microglia in the neuroinflammatory cascade, their polarization between pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes, and how this process influences neuronal damage and tissue repair. This review highlights the roles of the complement system, inflammasome activation, and blood–brain barrier disruption as key drivers of inflammation and neuronal injury. Additionally, we elaborate on the dynamic interactions between resident and infiltrating immune cells, which amplify inflammation and impede post-ischemic recovery. Finally, we discuss emerging therapeutic strategies targeting immune modulation, including cytokine regulation, microglial reprogramming, and targeted drug delivery systems, which offer promising avenues for improving outcomes in ischemic stroke. Full article

Nicotinamide mononucleotide, known as NMN, is an important nicotinamide adenine dinucleotide (NAD⁺) precursor. It is integral in cellular metabolism, energy generation, and processes associated with aging. Since NMN provides healthy value, it becomes a major focus for the biotechnological industry. This study presents a new biosynthetic pathway for producing NMN without limits on intracellular PRPP (5′-phosphoribosyl pyrophosphate) metabolic flux. The route started by converting cytidine into 1-phosphoribose via pyrimidine-nucleoside phosphorylase (PyNP), after transforming into nicotinamide riboside (NR) through either purine-nucleoside phosphorylase (XapA) or nicotinate riboside kinase (NRK). NR was phosphorylated by NRK in the presence of nicotinamide (NAM) to produce NMN. We established an in vitro enzyme activity verification system for the feasibility check. The optimization of multienzyme cascade reactions was figured out for the NMN biosynthesis. Finally, the enzymes of PyNP and NRK were expressed in the cytidine-producing strain; we established a de novo biosynthesis pathway from glucose to NMN, achieving a production titer of 33.71 mg/L at a shake-flask scale. Full article

The traditional recycling process of spent lithium-ion battery(LIB) with high Mn content faces the defects of high cost of neutralization and precipitation, poor economics of Mn extraction, and serious Li loss. Therefore, this paper introduces a comprehensive hydrometallurgical method for extracting valuable metals from high-Mn spent LIB. Particularly, directional precipitation of Mn was achieved by utilizing its redox properties, and shot-process extraction and enrichment of Li was realized by using the extractant HBL121. In a sulfuric acid system, control of the oxidant dosage to 0.8% resulted in high leaching efficiencies for Li, Ni, Co, and Mn, with values of 96.58%, 96.13%, 95.22%, and 94.24%, respectively, under optimal conditions which were C(H₂SO₄) of 3.5 mol/L, V(H₂O₂) of 0.8% (v/v), L/S of 10:1, temperature of 60 °C, and time of 60 min. Subsequently, the addition of KMnO₄ dosage (K_p/K_t) in a ratio of 1:1 resulted in the precipitation of 98.47% of Mn as MnO₂, with Ni and Li precipitation efficiencies of 0.2% and 0.1%, respectively. Cascade extraction of Ni and Co was reached by using Cyanex272 extractant from the solution after Mn precipitation. At an organic-to-aqueous phase ratio (O/A) of 1:5, the Co extraction efficiency reached 98.68%, whereas the loss efficiency of Ni was 5.53%, and Li was less than 0.1%. Adjusting the O/A to 1:1 increased the Ni extraction efficiency to 89.99% and Li loss to 8.95%. Finally, the HBL121 extractant was utilized to extract Li from the Li-rich solution, achieving 95.08% extraction efficiency. The Li was stripped with 2 mol/L H₂SO₄ from the load organic phase, realizing a Li concentration of 11.44 g/L. Thus, this process facilitates the comprehensive and efficient recovery of valuable metals such as Li, Ni, Co, and Mn from spent high-Mn LIB. Full article

One hundred and eighteen years have passed since Alzheimer’s disease (AD) was first diagnosed by Alois Alzheimer as a multifactorial and complex neurodegenerative disorder with psychiatric components. It is inaugurated by a cascade of events initiating from amnesic-type memory impairment leading to the gradual loss of cognitive and executive capacities. Pathologically, there is overwhelming evidence that clumps of misfolded amyloid-β (Aβ) and hyperphosphorylated tau protein aggregate in the brain. These pathological processes lead to neuronal loss, brain atrophy, and gliosis culminating in neurodegeneration and fueling AD. Thus, at a basic level, abnormality in the brain’s protein function is observed, causing disruption in the brain network and loss of neural connectivity. Nevertheless, AD is an aging disorder caused by a combination of age-related changes and genetic and environmental factors that affect the brain over time. Its mysterious pathology seems not to be limited to senile plaques (Aβ) and neurofibrillary tangles (tau), but to a plethora of substantial and biological processes, which have also emerged in its pathogenesis, such as a breakdown of the blood–brain barrier (BBB), patients carrying the gene variant APOE4, and the immuno-senescence of the immune system. Furthermore, type 2 diabetes (T2DM) and metabolic syndrome (MS) have also been observed to be early markers that may provoke pathogenic pathways that lead to or aggravate AD progression and pathology. There are numerous substantial AD features that require more understanding, such as chronic neuroinflammation, decreased glucose utilization and energy metabolism, as well as brain insulin resistance (IR). Herein, we aim to broaden our understanding and to connect the dots of the multiple comorbidities and their cumulative synergistic effects on BBB dysfunction and AD pathology. We shed light on the path-physiological modifications in the cerebral vasculature that may contribute to AD pathology and cognitive decline prior to clinically detectable changes in amyloid-beta (Aβ) and tau pathology, diagnostic biomarkers of AD, neuroimmune involvement, and the role of APOE4 allele and AD–IR pathogenic link—the shared genetics and metabolomic biomarkers between AD and IR disorders. Investment in future research brings us closer to knowing the pathogenesis of AD and paves the way to building prevention and treatment strategies. Full article

The acquisition of nighttime remote-sensing visible-light images is often accompanied by low-illumination effects and haze interference, resulting in significant image quality degradation and greatly affecting subsequent applications. Existing low-light enhancement and dehazing algorithms can handle each problem individually, but their simple cascade cannot effectively address unknown real-world degradations. Therefore, we design a joint processing framework, WFDiff, which fully exploits the advantages of Fourier–wavelet dual-domain features and innovatively integrates the inverse diffusion process through differentiable operators to construct a multi-scale degradation collaborative correction system. Specifically, in the reverse diffusion process, a dual-domain feature interaction module is designed, and the joint probability distribution of the generated image and real data is constrained through differentiable operators: on the one hand, a global frequency-domain prior is established by jointly constraining Fourier amplitude and phase, effectively maintaining the radiometric consistency of the image; on the other hand, wavelets are used to capture high-frequency details and edge structures in the spatial domain to improve the prediction process. On this basis, a cross-overlapping-block adaptive smoothing estimation algorithm is proposed, which achieves dynamic fusion of multi-scale features through a differentiable weighting strategy, effectively solving the problem of restoring images of different sizes and avoiding local inconsistencies. In view of the current lack of remote-sensing data for low-light haze scenarios, we constructed the Hazy-Dark dataset. Physical experiments and ablation experiments show that the proposed method outperforms existing single-task or simple cascade methods in terms of image fidelity, detail recovery capability, and visual naturalness, providing a new paradigm for remote-sensing image processing under coupled degradations. Full article

Brain tumors elicit complex neuropsychiatric disturbances that frequently occur prior to radiological detection and hinder differentiation from major psychiatric disorders. These syndromes stem from tumor-dependent metabolic reprogramming, neuroimmune activation, neurotransmitter dysregulation, and large-scale circuit disruption. Dinucleotide hypermethylation (e.g., IDH-mutant gliomas), through the accumulation of 2-hydroxyglutarate (2-HG), execute broad DNA and histone hypermethylation, hypermethylating serotonergic and glutamatergic pathways, and contributing to a treatment-resistant cognitive-affective syndrome. High-grade gliomas promote glutamate excitotoxicity via system Xc⁻ transporter upregulation that contributes to cognitive and affective instability. Cytokine cascades induced by tumors (e.g., IL-6, TNF-α, IFN-γ) lead to the breakdown of the blood–brain barrier (BBB), which is thought to amplify neuroinflammatory processes similar to those seen in schizophrenia spectrum disorders and autoimmune encephalopathies. Frontal gliomas present with apathy and disinhibition, and temporal tumors lead to hallucinations, emotional lability, and episodic memory dysfunction. Tumor-associated neuropsychiatric dysfunction, despite increasing recognition, is underdiagnosed and commonly misdiagnosed. This paper seeks to consolidate the mechanistic understanding of these syndromes, drawing on perspectives from neuroimaging, molecular oncology, neuroimmunology, and computational psychiatry. Novel approaches, including lesion-network mapping, exosomal biomarkers or AI-based predictive modeling, have projected early detection and precision-targeted interventions. In the context of the limitations of conventional psychotropic treatments, mechanistically informed therapies, including neuromodulation, neuroimmune-based interventions, and metabolic reprogramming, are essential to improving psychiatric and oncological outcomes. Paraneoplastic neuropsychiatric syndromes are not due to a secondary effect, rather, they are manifestations integral to the biology of a tumor, so they require a new paradigm in both diagnosis and treatment. And defining their molecular and circuit-level underpinnings will propel the next frontier of precision psychiatry in neuro-oncology, cementing the understanding that psychiatric dysfunction is a core influencer of survival, resilience, and quality of life. Full article

The progression of inflammation during sepsis represents a multifaceted biological cascade that requires effective therapeutic interventions to improve survival. In septic neonatal foals, oxidative stress (OS) arises due to a compromised antioxidant defense system. Oxidative stress may disrupt the functionality of redox-sensitive organelles, such as the endoplasmic reticulum (ER). Endoplasmic reticulum stress disorder affects multiple cellular signaling pathways, including redox balance, inflammation, and apoptosis, and contributes to the pathogenesis of sepsis. The study aimed to elucidate whether OS conditions in sepsis influenced gene expression associated with ER stress. Blood samples were collected from 7 healthy and 21 hospitalized neonatal foals and processed for RNA extraction. RNA sequencing was employed to identify ER stress-responsive genes. Novel findings reported here indicate activation of the ER stress pathway in foals with sepsis. Several genes associated with ER stress, such as clusterin (CLU), BCL2-like 1 (BCL2L1), ubiquitin specific peptidase 14 (USP14), bifunctional apoptosis regulator (BFAR), and optic atrophy 1 (OPA1), were upregulated and positively correlated with sepsis scores and negatively correlated with the combined activities of antioxidant enzymes. In contrast, X-box binding protein 1 (XBP1), homocysteine inducible ER protein with ubiquitin-like domain 1 (HERPUD1), leucine-rich repeat kinase 2 (LRRK2), and selenoprotein S (SELENOS) were negatively correlated with sepsis scores and were downregulated in sepsis and positively correlated with the combined activities of antioxidant enzymes. Furthermore, a positive correlation was observed between cAMP responsive element binding protein 3 like 2 (CREB3L2) and BCL2L1, as well as between the expressions of USP14 and YOD1 deubiquitinase (YOD1) in sepsis. Similarly, the expression levels of XBP1 and Herpud1 demonstrated a positive correlation with each other in sepsis. Additionally, the downregulation of genes with protective function against OS, such as XBP1, HERPUD1, and SELENOS, in septic foals also highlights their significance in mitigating OS in sepsis treatment. The study reported here highlights the potential of ER stress as a promising therapeutic target and prognostic marker in septic foals. Full article

Facial features are critical visual indicators for understanding what a person is experiencing, providing valuable insights into their emotions and physical states. However, accurately detecting these features under diverse conditions remains a significant challenge, especially in computationally constrained environments. This paper presents a facial feature extraction method designed to identify regions of interest for detecting facial cues, with a focus on improving the accuracy of eye and mouth detection. Addressing the limitations of standard Haar cascade classifiers, particularly in challenging scenarios such as droopy eyes, red eyes, and droopy mouths, this method introduces a correction algorithm rooted in normal human facial anatomy, emphasizing symmetry and consistent feature placement. By integrating this correction algorithm with a feature-based refinement process, the proposed approach enhances detection accuracy from 67.22% to 96.11%. Through this method, the accurate detection of facial features like the eyes and mouth is significantly improved, offering a lightweight and efficient solution for real-time applications while maintaining computational efficiency. Full article

Oxaliplatin-induced peripheral neurotoxicity (OIPN) represents a major challenge in cancer therapy, characterized by dorsal root ganglia (DRG) inflammation and disruption of neuro-glio-vascular unit function. In this study, we investigated the involvement of the scaffold protein IQ Motif Containing GTPase Activating Protein 1 (IQGAP1) and dehydropeptidase-1 (DPEP1) in the DRG response to oxaliplatin (OxPt) and the modulatory effect of cilastatin. Behavioral assessment showed a robust nocifensive response to cold stimuli in OxPt-treated rats, attenuated by cilastatin co-treatment. Our confocal study revealed different cellular and subcellular expression patterns of IQGAP1 and DPEP1 in neurons, glia, and endothelial cells, where both signals overlap approximately one-third. OxPt enhanced cytosolic aggregation of IQGAP1 in neurons and upregulation of signal in glia, accompanied by co-expression of TNFα and IL-6, indicating involvement in the inflammatory process. DPEP1 showed altered subcellular distribution in OxPt-treated animals, suggesting a potential role in the inflammatory cascade. Notably, IQGAP1 expression was diminished in endothelial membranes under OxPt, while cilastatin preserved endothelial IQGAP1-CD31 colocalization, suggesting partial restoration of blood-nerve barrier integrity. These findings identify IQGAP1 and DPEP1 as key players in DRG inflammation and position cilastatin as a promising modulator of OIPN through neuro-glio-vascular stabilization. Full article

Macroinvertebrates are a crucial part of aquatic ecosystems and significantly contribute to the maintenance of their health and stability. Our aims were to explore spatio-temporal patterns in macroinvertebrate communities and evaluate the ecological health of various parts of the Poyang Lake Basin during the early stage of a fishing ban. We collected samples using a Peterson grab sampler and conducted ecological evaluations using the B-IBI index. A total of 107 species of macroinvertebrates were identified, and most species were arthropods. The density and biomass of macroinvertebrates significantly differed among seasons and water bodies. No significant differences in diversity among seasons were observed; however, diversity significantly varied among water bodies. Environmental parameters such as water depth, pH, turbidity, total nitrogen, total phosphorus, and chlorophyll a played a crucial role in shaping the community structure of macroinvertebrates. Most of the sampling sites were classified as healthy or sub-healthy, indicating that the fishing ban policy has started to have a positive effect. The effects of this ban are achieved through a cascading sequence of processes, including the elimination of fishing disturbance, the restoration of habitat structure, and the reallocation of trophic energy, in addition to increases in microhabitat diversity associated with habitat heterogeneity. Together, these processes drive the multidimensional recovery of macroinvertebrate communities, manifested as increased species richness, higher density and biomass, and elevated B-IBI scores. Full article

Epstein-Barr Virus (EBV) is a causative agent of infectious mononucleosis and is strongly associated with Burkitt lymphoma, Hodgkin lymphoma, and nasopharyngeal carcinoma. EBV encodes a deubiquitinating enzyme, BPLF1, which is important for infectious virus production, B-cell immortalization, and tumorigenesis. To elucidate BPLF1’s role, an affinity-based mass spectrometry screen was performed, which suggested that BPLF1 and mTOR interact. mTOR, a critical mediator within cellular signaling cascades and oncogenesis, exists in two distinct complexes: mTOR Complex 1 (mTORC1) and mTOR Complex 2 (mTORC2). Here, we show that BPLF1 has direct deubiquitinating (DUB) activity on mTOR, removing both K48- and K63-ubiquitin linkages. Additionally, WT BPLF1 decreased mTORC1 localization to the lysosome and decreased the phosphorylation of mTORC1 downstream effectors, 4E-BP1 and S6K1. BPLF1 also had DUB activity on Raptor and Rictor, which have both been shown to preferentially cause the formation of mTORC2 over mTORC1 when not ubiquitinated. Immunoprecipitation of mTOR shows decreased mTORC1 formation in the presence of WT BPLF1. Importantly, treatment with rapamycin, an mTORC1 inhibitor, increased infectious virus production, while JR-AB2-011, an mTORC2 inhibitor, reduced infectious virus production. Taken together, these data demonstrate that BPLF1’s effect on the mTOR signaling cascade regulates cellular and viral processes during EBV infectivity and replication. Full article

Rod pump systems are complex nonlinear processes, and conventional efficiency prediction methods for such systems typically rely on high-order fractional partial differential equations, which severely constrain real-time inference. Motivated by the increasing availability of measured electrical power data, this paper introduces a series of prediction models for nonlinear fractional-order PDE systems efficiency based on multimodal feature fusion. First, three single-model predictions—Asymptotic Cross-Fusion, Adaptive-Weight Late-Fusion, and Two-Stage Progressive Feature Fusion—are presented; next, two ensemble approaches—one based on a Parallel-Cascaded Ensemble strategy and the other on Data Envelopment Analysis—are developed; finally, by balancing base-learner diversity with predictive accuracy, a multi-strategy ensemble prediction model is devised for online rod pump system efficiency estimation. Comprehensive experiments and ablation studies on data from 3938 oil wells demonstrate that the proposed methods deliver high predictive accuracy while meeting real-time performance requirements. Full article

Cleanrooms are a fundamental setup of every semiconductor and life science factory, representing strictly controlled ambient conditions designed to minimize the air contamination that could affect a product within the production process. A cleanroom pressure cascade is a technological process associated with the ventilation and air treatment in these plants, with the goal of keeping the rooms within strict parameters. From a control systems perspective, it represents an MIMO ensemble of coupled control loops related to the technological process of air dynamics. In this research, we solve the multivariable control problem and present a novel, systematic approach with a conceptual solution for the following: (1) technological process and modeling challenges; (2) system identification and black-box MIMO process modeling; (3) full-blown controller design with model predictive control in its central place. This research was conducted on a real system at the “Fabrika COVID Vakcina” factory in Belgrade, Serbia. Full article

The detection of gamma-ray burst GRB 221009A has attracted significant attention due to its record brightness and first-ever detection of multi-TeV $\mathit{\gamma }$-rays from a GRB. Located at redshift $z=0.151$, this event is relatively nearby by GRB standards yet remains cosmologically distant, making the survival of multi-TeV photons surprising. The Large High Altitude Air Shower Observatory detected photons with energies up to ∼13 TeV during the early afterglow phase, challenging standard EBL models. We investigate whether several theoretical frameworks can explain this anomalous emission: reduced EBL opacity due to cosmic voids along the line of sight, novel emission mechanisms within the GRB environment, secondary $\mathit{\gamma }$-ray production through cosmic-ray cascades, and new physics scenarios involving Lorentz invariance violation or axion-like particles. Our analysis reveals areas of consensus regarding the exceptional nature of this event, while highlighting ongoing theoretical tensions about the dominant physical processes. We discuss the limitations of current models and identify specific observational signatures that future multi-wavelength and multi-messenger observations could provide to discriminate between competing explanations. The continued study of similar events with next-generation facilities will be crucial for resolving these theoretical challenges and advancing our understanding of extreme particle acceleration processes in astrophysical environments. Full article

Basic Pentacysteine (BPC) represents a class of plant-exclusive transcription factors, serving pivotal roles in orchestrating developmental processes and mediating responses to both biotic and abiotic stressors. However, the genome-wide characteristics and low-temperature response mechanism of the BPC gene family in cotton remain unclear. Employing a genome-wide screening approach, this study characterized 60 distinct BPC transcription factor genes across ten Gossypium species. Conserved structural analysis showed that all BPC members carried a highly conserved GAGA-binding domain. Concurrently, the exploration of cis-acting elements within promoter regions demonstrated the potential involvement of these BPC transcription factors in modulating developmental processes, hormone signaling cascades, and abiotic stress adaptation mechanisms. Genomic collinearity analysis shows that segmental duplication is the core mechanism for the expansion of this gene family. Expression analysis indicated that the transcription level of GhBPC4 was significantly increased under low-temperature stress. Genetic function studies displayed that VIGS-mediated GhBPC4 silencing reduced cotton cold tolerance. This study systematically analyzed the genomic characteristics of the cotton BPC transcription factor family and functionally validated the molecular mechanism of GhBPC4-mediated cryogenic response. These findings establish an important foundation for subsequent analysis of multidimensional regulatory networks and the breeding of cold-resistant cotton germplasms. Full article