Verapamil modulates astrocytic glycolytic dysfunction via TXNIP inhibition in the hippocampus of 3 × Tg-AD mice.

Alzheimer's disease (AD) is a gradually worsening neurodegenerative condition marked by the accumulation of amyloid-β plaques and a decline in cognitive abilities. Emerging research emphasizes astrocytic metabolic disturbances as contributors to AD development. This study investigates the therapeutic effects of Verapamil (VPM), a clinically approved calcium channel blocker, on astrocytic glycolysis in 3 × Tg-AD mice, focusing on the involvement of the thioredoxin-interacting protein (TXNIP)/glucose transporter 1 (GLUT1) pathway.

Zwitterionic chitosan-modified amorphous ZnCuAl-LDH eye drops for efficient treatment of bacterial keratitis.

Bacterial keratitis caused by microbial invasion represents a significant cause of visual impairment characterized by corneal perforation, epithelial defect, intense pain, and conjunctival congestion. The widespread misuse of antibiotic eye drops in clinical treatment has accelerated the global rise of antibiotic-resistant infections, dimming the prospects for antibiotic therapy. In response, inorganic nanomaterial-based antibacterial eye drops have been developed for bacterial keratitis leveraging their structural controllability, composition diversity and ease of functionalization, However, they typically exert antibacterial effects with the assistance of laser, ultrasound, or X-ray irradiation that may cause irritation or damage to the human eye, or involve intricate structural modifications for antibacterial activation.

Rhythmic TDP-43 affects RNA splicing of USP13, resulting in alteration of BMAL1 ubiquitination.

Circadian rhythm disorders are common characteristics of neurodegenerative diseases. The pathological aggregation of transactive response DNA-binding protein 43 (TDP-43) is associated with multiple neurodegenerative diseases, such as amyotrophic lateral sclerosis. However, the relationship between TDP-43 and circadian rhythm remains unknown.

Associations between air pollution and daily outpatient visits for dry eye disease and the effect modification of temperature.

Background: Dry eye disease (DED) is one of the most common ocular surface disorders caused by various contributors. Air pollutants are considered a risk factor for ocular surface diseases. We aimed to investigate the associations between air pollutants (PM, PM, NO, SO, CO and O) and PM constituents and daily outpatient visits for DED, as well as the modifying effect of temperature on the associations.

Halide-free deep eutectic solvents constructed from natural compounds for converting carbon dioxide to cyclic carbonate.

Halide-free deep eutectic solvents (DESs) derived from natural biological compounds were used to gently catalyze the cycloaddition reaction between CO and epoxides, with a TOF of 645 h. The DFT calculation result was in good agreement with the experiment result, indicating that the ring closure process was the rate-determining step.

An injectable shape-adaptive hydrogel system for subconjunctival injuries: and permanently releases rapamycin to prevent fibrosis promoting autophagy.

Subconjunctival fibrosis (SCF) is a common and refractory eye disease that is a serious threat to vision. The severe side effects of existing drugs and low drug bioavailability due to the ocular barrier are major challenges in SCF treatment. Hence, there is an urgent need to explore safer and more effective strategies for administering anti-SCF drugs.

Sex-Stratified Bidirectional Mendelian Randomization Analysis of Eating Habits and Female Pelvic Peritoneal Adhesions.

Background: Female pelvic peritoneal adhesions (FPPA) represent a significant global health burden. Dietary habits play a crucial role in health outcomes, yet their influence on FPPA remains unclear. This study aims to explore the bidirectional causal relationships between 72 eating habits and FPPA using sex-stratified Mendelian randomization (MR).

Tau Isoform-Regulated Schwann Cell Proliferation and Migration Improve Peripheral Nerve Regeneration After Injury.

Tau is a microtubule-associated protein that plays a vital role in the mammalian nervous system. Alternative splicing of the gene leads to the formation of tau isoforms with varying N-terminal inserts and microtubule-binding repeats. Dysregulation of tau alternative splicing has been linked to diseases in the central nervous system, but the roles of tau isoforms in the peripheral nervous system remain unclear.

Modification effects of immigration status and comorbidities on associations of heat and heatwave with stroke morbidity.

Background: Heat and heatwave have been associated with stroke morbidity, but it is still unclear whether immigrants from different geographic regions and patients with comorbidity are more vulnerable to heat and heatwave.

Methods: Time-stratified case-crossover design combined with generalized additive quasi-Poisson models were used to quantify the relative risks (RRs) of heat and heatwave on first-ever stroke morbidity during 0-7 lag days. Attributable fractions (AFs) were estimated to assess the first-ever stroke morbidity burden due to heat and heatwave.

Celastrol alleviates subconjunctival fibrosis induced by silicone implants mimicking glaucoma surgery.

Subconjunctival fibrosis is critical to the outcomes of several ophthalmic conditions or procedures, such as glaucoma filtering surgery. This study aimed to investigate the anti-fibrotic effect of celastrol on subconjunctival fibrosis and to further reveal the underlying mechanisms. We used celastrol-loaded nanomicelles hydrogel hybrid as a sustained-release drug.

Dual-ROS-scavenging and dual-lingering nanozyme-based eye drops alleviate dry eye disease.

Efficiently removing excess reactive oxygen species (ROS) generated by various factors on the ocular surface is a promising strategy for preventing the development of dry eye disease (DED). The currently available eye drops for DED treatment are palliative, short-lived and frequently administered due to the short precorneal residence time. Here, we developed nanozyme-based eye drops for DED by exploiting borate-mediated dynamic covalent complexation between n-FeZIF-8 nanozymes (n-Z(Fe)) and poly(vinyl alcohol) (PVA) to overcome these problems.

Dual-specificity tyrosine phosphorylation-regulated kinase 1A promotes the inclusion of amyloid precursor protein exon 7.

Extracellular amyloid plaques made of Amyloid-β (Aβ) derived from amyloid precursor protein (APP) is one of the major neuropathological hallmarks of Alzheimer's disease (AD). There are three major isoforms of APP, APP, APP, and APP generated by alternative splicing of exons 7 and 8. Exon 7 encodes the Kunitz protease inhibitor (KPI) domain.

An injectable thermoresponsive-hydrogel for lamellar keratoplasty: In-situ releases celastrol and hampers corneal scars.

Corneal stromal fibrosis is a common cause of visual impairment resulting from corneal injury, inflammation and surgery. Therefore, there is an unmet need for inhibiting corneal stromal fibrosis. However, bioavailability of topical eye drops is very low due to the tear and corneal barriers.

Dual-Atom Nanozyme Eye Drops Attenuate Inflammation and Break the Vicious Cycle in Dry Eye Disease.

Dry eye disease (DED) is a major ocular pathology worldwide, causing serious ocular discomfort and even visual impairment. The incidence of DED is gradually increasing with the high-frequency use of electronic products. Although inflammation is core cause of the DED vicious cycle, reactive oxygen species (ROS) play a pivotal role in the vicious cycle by regulating inflammation from upstream.

M2 macrophages promote subconjunctival fibrosis through YAP/TAZ signalling.

Purpose: To evaluate the role of M2 macrophages in subconjunctival fibrosis after silicone implantation (SI) and investigate the underlying mechanisms.

Materials And Methods: A model of subconjunctival fibrosis was established by SI surgery in rabbit eyes. M2 distribution and collagen deposition were evaluated by histopathology.

Neuronal aerobic glycolysis exacerbates synapse loss in aging mice.

Brain consumes nearly 20% supply of energy from glucose metabolism by oxidative phosphorylation and aerobic glycolysis. Less active state of glycolytic enzymes results in a limited capacity of glycolysis in the neurons of adult brain. Here we identified that Warburg effect is enhanced in hippocampal neurons during aging.

Tau truncation in the pathogenesis of Alzheimer's disease: a narrative review.

Alzheimer's disease is characterized by two major neuropathological hallmarks-the extracellular β-amyloid plaques and intracellular neurofibrillary tangles consisting of aggregated and hyperphosphorylated Tau protein. Recent studies suggest that dysregulation of the microtubule-associated protein Tau, especially specific proteolysis, could be a driving force for Alzheimer's disease neurodegeneration. Tau physiologically promotes the assembly and stabilization of microtubules, whereas specific truncated fragments are sufficient to induce abnormal hyperphosphorylation and aggregate into toxic oligomers, resulting in them gaining prion-like characteristics.

Two simple assays for assessing the seeding activity of proteopathic tau.

The regional distribution of neurofibrillary tangles of hyperphosphorylated tau aggregates is associated with the progression of Alzheimer's disease (AD). Misfolded proteopathic tau recruits naïve tau and templates its misfolding and aggregation in a prion-like fashion, which is believed to be the molecular basis of propagation of tau pathology. A practical way to assess tau seeding activity is to measure its ability to recruit/bind other tau molecules and to induce tau aggregation.

A dicyanoisophorone-based ICT fluorescent probe for the detection of Hg in water/food sample analysis and live cell imaging.

Mercury ions are notoriously difficult to biodegradable, and its abnormal bioaccumulation in the human body through the food chain can cause various diseases. Therefore, the quantitative and real-time detection of Hg is very extremely important. Herein, we have brilliant designed and synthesized (E)-O-(4-(2-(3-(dicyanomethylene)-5,5-dimethylcyclohex-1-en-1-yl)vinyl)phenyl) O-phenyl carbonothioate (ICM-Hg) as a selective fluorescent probe for Hg detection in real samples and intracellular staining.

Celastrol Alleviates Corneal Stromal Fibrosis by Inhibiting TGF-β1/Smad2/3-YAP/TAZ Signaling After Descemet Stripping Endothelial Keratoplasty.

Purpose: The purpose of this study was to investigate the effect of celastrol (CEL) on corneal stromal fibrosis after Descemet stripping endothelial keratoplasty (DSEK) and its associated mechanism.

Methods: Rabbit corneal fibroblasts (RCFs) were isolated, cultured, and identified. A CEL-loaded positive nanomedicine (CPNM) was developed to enhance corneal penetration.

Passive immunization inhibits tau phosphorylation and improves recognition learning and memory in 3xTg-AD mice.

Tau pathology is essential in the pathogenesis of Alzheimer's disease (AD) and related tauopathies. Tau immunotherapy aimed at reducing the progression of tau pathology provides a potential therapeutic strategy for treating these diseases. By screening monoclonal antibodies 43D, 63B, 39E10, and 77G7 that recognize epitopes ranging from tau's N-terminus to C-terminus, we found the 77G7, which targets the microtubule-binding domain promoted tau clearance in a dose-dependent manner by entering neuronal cells in vitro.

Defect Surface Engineering of Hollow NiCoS Nanoprisms towards Performance-Enhanced Non-Enzymatic Glucose Oxidation.

Transition metal sulfides have been explored as electrode materials for non-enzymatic detection. In this work, we investigated the effects of phosphorus doping on the electrochemical performances of NiCoS electrodes (P-NiCoS) towards glucose oxidation. The fabricated non-enzymatic biosensor displayed better sensing performances than pristine NiCoS, with a good sensitivity of 250 µA mM cm, a low detection limit (LOD) of 0.

Organic radicals stabilization above 300 °C in Eu-based coordination polymers for solar steam generation.

Organic radicals feature unpaired electrons, and these compounds may have applications in biomedical technology and as materials for solar energy conversion. However, unpaired electrons tend to pair up (to form chemical bonds), making radicals unstable and hampering their applications. Here we report an organic radical system that is stable even at 350 °C, surpassing the upper temperature limit (200 °C) observed for other organic radicals.

Prism-like bimetallic (Ni-Co) alkaline carboxylate-based non-enzymatic sensor capable of exceptionally high catalytic activity towards glucose.

In this study, we fabricated a novel non-enzymatic glucose sensor based on prism-like bimetallic alkaline carboxylate (CoNi-MIM). The morphology and structure of CoNi-MIM were carefully investigated by scanning electron microscopy (SEM), transmission electron microscopy (TEM), powder X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). The electrochemical glucose oxidation of the synthesized sensor was then explored by cyclic voltammetry (CV) and chronoamperometry in alkaline medium.