Sex and region-specific disruption of autophagy and mitophagy in Alzheimer's disease: linking cellular dysfunction to cognitive decline.

Macroautophagy and mitophagy are critical processes in Alzheimer's disease (AD), yet their links to behavioral outcomes, particularly sex-specific differences, are not fully understood. This study investigates autophagic (LC3B-II, SQSTM1) and mitophagic (BNIP3L, BNIP3, BCL2L13) markers in the cortex and hippocampus of male and female 3xTg-AD mice, using western blotting, transmission electron microscopy (TEM), and behavioral tests (novel object recognition and novel object placement). Significant sex-specific differences emerged: female 3xTg-AD mice exhibited autophagosome accumulation due to impaired degradation in the cortex, while males showed fewer autophagosomes, especially in the hippocampus, without significant degradation changes.

Achieving partial nitrification and denitrification coupled with simultaneous partial nitrification, anammox, and denitrification (PND-SNAD) by the inhibition of sulfide to accomplish stabilized nitrogen removal.

The simultaneous partial nitrification, anammox, and denitrification (SNAD) process is widely applied for treating high-ammonia wastewater, but its application to low-ammonia organic wastewater has been scarcely explored. In this study, a partial nitrification and denitrification coupled with simultaneous partial nitrification, anammox, and denitrification (PND-SNAD) system was established to treat organic wastewater with low ammonia concentration. Experimental results revealed that sulfide at 5 mg/L selectively inhibited nitrite-oxidizing bacteria (NOB) but had little effect on ammonium-oxidizing bacteria (AOB).

Effective organic matter removal via bio-adsorption prior to anammox process and utilization of carbon-rich sludge.

Excessive organic matter in the anaerobic ammonia oxidation (Anammox) leads to the growth of a large number of heterotrophic bacteria, which disrupts the anaerobic ammonia oxidation. The adsorption-anaerobic ammonia oxidation process can effectively reduce excessive organic matter, capturing it instead of consuming it, which is a sustainable development technology. In this study, utilizing the excellent adsorption performance of aerobic granular sludge (AGS), an adsorption-regeneration process was employed to remove organic matter at the front end of the Anammox process through bio-adsorption in an artificial simulated domestic sewage environment, and it was successfully used for denitrification.

Sex and Region-Specific Disruption of Autophagy and Mitophagy in Alzheimer's Disease: Linking Cellular Dysfunction to Cognitive Decline.

Macroautophagy and mitophagy are critical processes in Alzheimer's disease (AD), yet their links to behavioral outcomes, particularly sex-specific differences, are not fully understood. This study investigates autophagy (LC3B-II, SQSTM1) and mitophagy (BNIP3L, BNIP3, BCL2L13) markers in the cortex and hippocampus of male and female 3xTg-AD mice, using western blotting, transmission electron microscopy (TEM), and behavioral tests (novel object recognition and novel object placement). Significant sex-specific differences emerged: female 3xTg-AD mice exhibited autophagosome accumulation due to impaired degradation in the cortex, while males showed fewer autophagosomes, especially in the hippocampus, without significant degradation changes.

Ultra-Low-Dose UV-C Photo-stimulation Promotes Neural Stem Cells Differentiation via Presenilin 1 Mediated Notch and β-Catenin Activation.

Light-based photo-stimulation has demonstrated promising effects on stem cell behavior, particularly in optimizing neurogenesis. However, the precise parameters for achieving optimal results, including the wavelengths, light intensity, radiating energy, and underlying mechanisms, remain incompletely understood. In this study, we focused on utilizing ultraviolet-C (UV-C) at a specific wavelength of 254 nm, with an ultra-low dose at intensity of 330 μW/cm and a total energy of 594 mJ/cm per day over a period of seven days, to stimulate the proliferation and differentiation of mouse neural stem cells (NSCs).

Oxidized SOD1 accelerates cellular senescence in neural stem cells.

Background: Neural stem cells (NSCs), especially human NSCs, undergo cellular senescence characterized by an irreversible proliferation arrest and loss of stemness after prolonged culture. While compelling correlative data have been generated to support the oxidative stress theory as one of the primary determinants of cellular senescence of NSCs, a direct cause-and-effect relationship between the accumulation of oxidation-mediated damage and cellular senescence of NSCs has yet to be firmly established. Human SOD1 (hSOD1) is susceptible to oxidation.

C1q is essential for myelination in the central nervous system (CNS).

Myelin sheath in the central nervous system (CNS) is essential for efficient action potential conduction. Microglia, the macrophages in the CNS, are suggested to regulate myelin development. However, the specific involvement of microglia in initial myelination is yet to be elucidated.

ALS-linked SOD1 mutations impair mitochondrial-derived vesicle formation and accelerate aging.

Oxidative stress (OS) is regarded as the dominant theory for aging. While compelling correlative data have been generated to support the OS theory, a direct cause-and-effect relationship between the accumulation of oxidation-mediated damage and aging has not been firmly established. Superoxide dismutase 1 (SOD1) is a primary antioxidant in all cells.

Selective removal of misfolded SOD1 delays disease onset in a mouse model of amyotrophic lateral sclerosis.

Background: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease. There is no cure currently. The discovery that mutations in the gene SOD1 are a cause of ALS marks a breakthrough in the search for effective treatments for ALS.

Background and roles: myosin in autoimmune diseases.

The myosin superfamily is a group of molecular motors. Autoimmune diseases are characterized by dysregulation or deficiency of the immune tolerance mechanism, resulting in an immune response to the human body itself. The link between myosin and autoimmune diseases is much more complex than scientists had hoped.

Mitochondrial dysfunction in aging.

Aging is a complex process that features a functional decline in many organelles. Although mitochondrial dysfunction is suggested as one of the determining factors of aging, the role of mitochondrial quality control (MQC) in aging is still poorly understood. A growing body of evidence points out that reactive oxygen species (ROS) stimulates mitochondrial dynamic changes and accelerates the accumulation of oxidized by-products through mitochondrial proteases and mitochondrial unfolded protein response (UPR).

The Initial Myelination in the Central Nervous System.

Myelination contributes not only to the rapid nerve conduction but also to axonal insulation and protection. In the central nervous system (CNS), the initial myelination features a multistep process where oligodendrocyte precursor cells undergo proliferation and migration before differentiating into mature oligodendrocytes. Mature oligodendrocytes then extend processes and wrap around axons to form the multilayered myelin sheath.

Carbon monoxide preconditioning is mediated via activation of mitochondrial-derived vesicles.

Preconditioning with inhalative carbon monoxide (CO) at low concentrations provides protection against hypoxic and ischemic insults in the brain and heart. The present study aims to test a hypothesis that activation of mitochondrial-derived vesicles (MDVs) is a mechanism underlying the protective effect of CO preconditioning. Here we show that CO preconditioning induced mild oxidative stress and activated massive production of MDVs.

Cerebral Ischemic Preconditioning Aggravates Death of Oligodendrocytes.

Neurodegeneration can benefit from ischemic preconditioning, a natural adaptive reaction to sublethal noxious stimuli. Although there is growing interest in advancing preconditioning to preserve brain function, preconditioning is not yet considered readily achievable in clinical settings. One of the most challenging issues is that there is no fine line between preconditioning stimuli and lethal stimuli.

4,8-dicarboxyl-8,9-iridoid-1-glycoside Promotes Neural Stem Cell Differentiation Through MeCP2.

Background: Borojó (Borojoa patinoi Cuatrec) fruit has recently been shown to have a variety of health benefit, but the mechanisms have been little studied. The aim of this study was to investigate the effect of 4,8-dicarboxyl-8,9-iridoid-1-glycoside (388) on proliferation and differentiation of embryonic neural stem cells (NSCs).

Methods: NSCs were treated with 388 and stem cell differentiation was determined by western blotting and immunofluorescence staining.

Ketogenic diet protects myelin and axons in diffuse axonal injury.

Background: Ketogenic diet (KD) has been identified as a potential therapy to enhance recovery after traumatic brain injury (TBI). Diffuse axonal injury (DAI) is a common type of traumatic brain injury that is characterized by delayed axonal disconnection. Previous studies showed that demyelination resulting from oligodendrocyte damage contributes to axonal degeneration in DAI.

Selective Susceptibility of Oligodendrocytes to Carbon Monoxide Poisoning: Implication for Delayed Neurologic Sequelae (DNS).

Delayed neurologic sequelae (DNS) are recurrent-transient neuropsychiatric consequences of carbon monoxide (CO) intoxication. Pathologically DNS features damages to the brain white matter. Here we test a hypothesis that direct cytotoxicity of CO to oligodendrocytes plays a role in the development of DNS.

Compromised Lactate Efflux Renders Vulnerability of Oligodendrocyte Precursor Cells to Metabolic Stresses.

Among the brain cells, oligodendrocyte progenitor cells (OPCs) are the most vulnerable in response to hypoxic and ischemic insults, of which the mechanism remains unknown. Brain cells are known to import or export lactate via differentially expressed monocarboxylate transporters (MCTs) to maintain energy metabolism and pH homeostasis. The present study aims to determine the role of MCT1 in the high vulnerability of OPCs.

Manipulable Permeability of Nanogel Encapsulation on Cells Exerts Protective Effect against TNF-α-Induced Apoptosis.

Cell encapsulation using microgel and nanogel, as a strategy of cell surface engineering, can mimic the niches of cells and organoids. The established niche that seasons cells and tissues for the controllable development underlies the superiority of encapsulation on cells. Encapsulation by layer-by-layer nanogel coating is a bottom-up simulation of extracellular matrices via nano- or micropackaging of cells in a multiscale way.

Monocarboxylate transporter 1 and the vulnerability of oligodendrocyte lineage cells to metabolic stresses.

Aims: Oligodendrocytes, especially oligodendrocyte precursor cells, are known to be sensitive to hypoxic and metabolic stresses. Vulnerability of oligodendrocytes is considered a contributing factor to white matter dysfunction. However, little is known about the energy processing characteristics of oligodendrocyte lineage cells under basal and metabolic stress conditions.

Neuroprotection by Combined Administration with Maslinic Acid, a Natural Product from Olea europaea, and MK-801 in the Cerebral Ischemia Model.

Glutamate-mediated excitotoxicity is a major cause of ischemic brain damage. MK-801 confers neuroprotection by attenuating the activation of the N-methyl-d-aspartate (NMDA) receptor, but it failed in clinical use due to the short therapeutic window. Here we aim to investigate the effects of maslinic acid, a natural product from Olea europaea, on the therapeutic time window and dose range for the neuroprotection of MK-801.

Shengmai injection attenuates the cerebral ischemia/reperfusion induced autophagy via modulation of the AMPK, mTOR and JNK pathways.

Context Shengmai injection (SMI) is a patented Chinese medicine originated from the ancient Chinese herbal compound Shengmai san, which is used extensively for the treatment of cardiovascular and cerebrovascular disease in the clinic. Objective To determine the neuroprotective effect of SMI, we investigated the effect of SMI on cerebral ischemia/reperfusion (I/R) injury in mice as well as the mechanisms underlying this effect. Materials and methods Right middle cerebral artery was occluded by inserting a thread through internal carotid artery for 1 h, and then reperfused for 24 h in mice.

Mevalonate Cascade and Neurodevelopmental and Neurodegenerative Diseases: Future Targets for Therapeutic Application.

The mevalonate cascade is a key metabolic pathway that regulates a variety of cellular functions and is thereby implicated in the pathophysiology of most brain diseases, including neurodevelopmental and neurodegenerative disorders. Emerging lines of evidence suggest that statins and Rho GTPase inhibitors are efficacious and have advantageous properties in treatment of different pathologic conditions that are relevant to the central nervous system. Beyond the original role of statins in lowering cholesterol synthesis, they have anti-inflammatory, antioxidant and modulatory effects on signaling pathways.