Cellular and molecular mechanisms of the blood-brain barrier dysfunction in neurodegenerative diseases.

BACKGROUND: Maintaining the structural and functional integrity of the blood-brain barrier (BBB) is vital for neuronal equilibrium and optimal brain function. Disruptions to BBB performance are implicated in the pathology of neurodegenerative diseases. MAIN BODY: Early indicators of multiple neurodegenerative disorders in humans and animal models include impaired BBB stability, regional cerebral blood flow shortfalls, and vascular inflammation associated with BBB dysfunction. Understanding the cellular and molecular mechanisms of BBB dysfunction in brain disorders is crucial for elucidating the sustenance of neural computations under pathological conditions and for developing treatments for these diseases. This paper initially explores the cellular and molecular definition of the BBB, along with the signaling pathways regulating BBB stability, cerebral blood flow, and vascular inflammation. Subsequently, we review current insights into BBB dynamics in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. The paper concludes by proposing a unified mechanism whereby BBB dysfunction contributes to neurodegenerative disorders, highlights potential BBB-focused therapeutic strategies and targets, and outlines lessons learned and future research directions. CONCLUSIONS: BBB breakdown significantly impacts the development and progression of neurodegenerative diseases, and unraveling the cellular and molecular mechanisms underlying BBB dysfunction is vital to elucidate how neural computations are sustained under pathological conditions and to devise therapeutic approaches.

Robust and Flexible Rubber Composite with High Photothermal Properties Achieved by In Situ ZDMA Assisted Dispersion of Eumelanin and its Hydrophobic Photothermal Application.

Eumelanin, a natural, biocompatible, and biodegradable photothermal agent derived from biomass, has attracted increasingly considerable attention due to its outstanding photothermal conversion efficiency. Unfortunately, its tendency to aggregate in flexible non-polar polymers, owing to its abundant polar groups on the surface, severely restricted the application of eumelanin in photothermal composite field. Herein, a feasible strategy is proposed to disperse eumelanin in non-polar rubber matrix via in situ generation of Zinc dimethacrylate (ZDMA). The graft-polymerization of ZDMA promotes the interfacial compatibility between styrene butadiene rubber (SBR) and eumelanin, achieving a uniform dispersion of eumelanin in SBR. The rubber composite exhibits a considerable tensile strength of 11.4 MPa, acceptable elongation at break of 146%, and outstanding photothermal conversion efficiency of up to 75.2% with only 1 wt% of eumelanin. Furthermore, based on the easy-processing of SBR matrix, the composite is treated with a sandpaper template technique and sprayed with trimethoxy(1H,1H,2H,2H-perfluorodecyl)silane (PFDTMS) to endow the material with near superhydrophobicity (water contact angle of 147.9°) capacity. Hydrophobicity provides excellent icing resistance, with droplet surfaces extending more than twice as long to freeze. Moreover, this hydrophobic photothermal material exhibits remarkable anti-frosting, de-frosting, and de-icing capabilities.

Self-Assembly for Creating Vertically-Aligned Graphene Micro Helices with Monolayer Graphene as Chiral Metamaterials.

Graphene's emergence enables creating chiral metamaterials in helical shapes for terahertz (THz) applications, overcoming material limitations. However, practical implementation remains theoretical due to fabrication challenges. This paper introduces a dual-component self-assembly technique that enables creating vertically-aligned continuous monolayer graphene helices at microscale with great flexibility and high controllability. This assembly process not only facilitates the creation of 3D microstructures, but also positions the 3D structures from a horizontal to a vertical orientation, achieving an aspect ratio (height/width) of ≈2700. As a result, an array of vertically-aligned graphene helices is formed, reaching up to 4 mm in height, which is equivalent to 4 million times the height of monolayer graphene. The benefit of these 3D chiral structures made from graphene is their capability to infinitely extend in height, interacting with light in ways that are not possible with traditional 2D layering methods. Such an impressive height elevates a level of interaction with light that far surpasses what is achievable with traditional 2D layering methods, resulting in a notable enhancement of optical chirality properties. This approach is applicable to various 2D materials, promising advancements in innovative research and diverse applications across fields.

Efficient Host Materials for Lithium-Sulfur Batteries: Ultrafine CoP Nanoparticles in Black Phosphorus-Carbon Composite.

The pursuit of efficient host materials to address the sluggish redox kinetics of sulfur species has been a longstanding challenge in advancing the practical application of lithium-sulfur batteries. In this study, amorphous carbon layer loaded with ultrafine CoP nanoparticles prepared by a one-step in situ carbonization/phosphating method to enhance the inhibition of 2D black phosphorus (BP) on LiPSs shuttle. The carbon coating layer facilitates accelerated electron/ion transport, enabling the active involvement of BP in the conversion of soluble lithium polysulfides (LiPSs). Concurrently, the ultra-fine CoP nanoparticles enhance the chemical anchoring ability and introduce additional catalytic sites. As a result, S@BP@C-CoP electrodes demonstrate exemplary cycling stability (with a minimal capacity decay of 0.054 % over 500 cycles at 1 C) and superior rate performance (607.1 mAh g-1 at 5 C). Moreover, at a sulfur loading of 5.5 mg cm-2, the electrode maintains an impressive reversible areal capacity of 5.45 mAh cm-2 after 50 cycles at 0.1 C. This research establishes a promising approach, leveraging black phosphorus-based materials, for developing high-efficiency Li-S batteries.

The Efficacy of Tiaoshen Acupuncture in Traditional Chinese Medicine for Insomnia Treatment: A Systematic Review and Meta-analysis.

Background: In recent years, Tiaoshen acupuncture in Traditional Chinese Medicine (TCM) has been employed for treating patients with insomnia, but the clinical efficacy remains to be substantiated. Objective: To assess the efficacy and safety of acupuncture in treating insomnia using the Tiaoshen method in TCM. Design: A systematic review and meta-analysis was conducted. Setting: The research was conducted in Shenzhen. Methods: Electronic databases, including Chinese National Knowledge Infrastructure (CNKI), Wanfang, SinoMed, Weipu, PubMed, Web of Science, EMBASE, and Cochrane databases, were retrieved up to September 15, 2023. Randomized controlled trials (RCTs) meeting inclusion criteria were screened. Quality assessment of included articles was performed using the Cochrane Risk of Bias tool. Valid data were then extracted and analyzed via meta-analysis using Review Manager 5.3. The study was registered in the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), 2023100051. Results: A total of 13 articles were included, comprising 849 patients with insomnia (diagnosed as chronic insomnia or primary insomnia). Meta-analysis results indicated that acupuncture with the Tiaoshen method could decrease the Pittsburgh Sleep Quality Index (PSQI) score [RR=-3.03, 95% CI (-3.73, -2.33), P < .00001], hyperarousal (HAS) scale score [RR=-7.75, 95% CI (-12.29, -3.22), P < .0008], and fatigue scale-14 (FS-14) score [RR=-2.11, 95% CI (-2.83, -1.38), P < .00001] compared with superficial acupuncture on non-effective acupoints or conventional acupuncture manipulation. Additionally, acupuncture with the Tiaoshen method demonstrated safety. However, the funnel plot suggested the presence of publication bias. Conclusions: Acupuncture with the Tiaoshen method could enhance sleep quality and efficiency. Due to the low quality of some literature, further high-quality RCTs are needed to improve the level of evidence.

Simultaneous qualitative and quantitative determination of 104 fat-soluble synthetic dyes in foods using disperse solid-phase extraction and UHPLC-Q-Orbitrap HRMS analysis.

Public exposure to synthetic dyes through foods has attracted ongoing and serious attention. Here we developed and validated a simultaneous screening and quantitation method for the analysis of fat-soluble synthetic dyes that most frequently found in foods, using C18 d-SPE clean-up and UHPLC-Q-Orbitrap HRMS on Full-MS/dd-MS2 mode. During a single run, 104 dyes including 6 pairs of isomers were distinguished based on chromatographic separation and unique product ions. The method showed satisfactory linearity (R > 0.99), recoveries (61.3 %-118.8 %), precision (<20 %) and limit of quantification (0.05-0.5 mg/kg). For 98 % of test dyes, screening detection limits ranged from 2.5 to 25 µg/kg. The validated method was successfully applied to real commercial foodstuffs revealing the presence of two selected illegal dyes in three samples.

Targeting the dynamics of cancer metabolism in the era of precision oncology.

Cancer metabolic reprogramming is a promising target for cancer therapy. The progression of tumors, including their growth, development, metastasis, and spread, is a dynamic process that varies over time and location. This means that the metabolic state of tumors also fluctuates. A recent study found that energy production efficiency is lower in solid tumors but increases significantly in tumor metastasis. Despite its importance for targeted tumor metabolism therapy, few studies have described the dynamic metabolic changes of tumors. In this commentary, we discuss the limitations of past targeted tumor metabolism therapy and the key findings of this study. We also summarize its immediate clinical implications for dietary intervention and explore future research directions for understanding the dynamic changes in tumor metabolic reprogramming.

Intraoperative Neck Angles in Endoscopic and Microscopic Otologic Surgeries.

OBJECTIVE: To quantitatively compare the ergonomic risk of otologic surgeries performed with endoscopes and microscopes. STUDY DESIGN: Observational cross-sectional study. SETTING: Operating room of a tertiary academic medical center. METHODS: Intraoperative neck angles of otolaryngology attendings, fellows, and residents were assessed during 17 otologic surgeries using inertial measurement unit sensors. Sensors were attached midline between the shoulder blades and on the posterior scalp of participants and were calibrated just prior to beginning each case. Quaternion data were used to calculate neck angles during periods of active surgery. RESULTS: Endoscopic and microscopic cases included similar percentages of time in high-risk neck positions, 75% and 73%, respectively, according to a validated ergonomic risk assessment tool, the Rapid Upper Limb Assessment. However, microscopic cases included a higher percentage of time spent in extension (25%) compared to endoscopic cases (12%) (p < .001). When examining the magnitude of average flexion and extension angles, endoscopic and microscopic cases were not significantly different. CONCLUSION: Utilizing intraoperative sensor data, we found that both endoscopic and microscopic approaches in otologic surgery were associated with high-risk neck angles, which can result in sustained neck strain. These results suggest that optimal ergonomics may be better achieved by the consistent application of basic ergonomic principles than by changing the technology in the operating room.

Covalent Grafting of 5-Aminolevulinic Acid onto Polylactic Acid Films and Their Photodynamic Potency in Preserving Salmon.

A novel photodynamic inactivation (PDI)-mediated antimicrobial film of polylactic acid/5-aminolevulinic acid (PLA/ALA) was successfully fabricated by a covalent grafting method using low-temperature plasma. The chemical structure, surface morphology, hydrophilic ability, and mechanical and barrier properties of the films were characterized, and their antibacterial, anti-biofilm potency and preservation effects on ready-to-eat salmon were investigated during storage. Results showed that the amino group of ALA was covalently grafted with the carboxyl group on the surface of PLA after the plasma treatment, with the highest grafting rate reaching ∼50%. The fabricated PLA/ALA films displayed an enhanced barrier ability against water vapor and oxygen. Under blue light-emitting diode illumination, the PLA/ALA films generated massive reactive oxygen species from the endogenous porphyrins in cells induced by ALA and then fatally destroyed the cell wall of planktonic cells and the architectural structures of sessile biofilms of the pathogens (Listeria monocytogenes and Vibrio parahaemolyticus) and spoilage bacterium (Shewanella putrefaciens). More importantly, the PDI-mediated PLA/ALA films potently inhibited 99.9% native bacteria on ready-to-eat salmon and significantly suppressed the changes of its drip loss, pH, and lipid oxidation (MDA) during storage, and on this basis, the shelf life of salmon was extended by 4 days compared with that of the commercial polyethylene film. Therefore, the PDI-mediated PLA/ALA films are valid in inactivating harmful bacterial and preserving the quality of seafood.

Sox11b regulates the migration and fate determination of Müller glia-derived progenitors during retina regeneration in zebrafish.

The transcription factor Sox11 plays important roles in retinal neurogenesis during vertebrate eye development. However, its function in retina regeneration remains elusive. Here we report that Sox11b, a zebrafish Sox11 homolog, regulates the migration and fate determination of Müller glia-derived progenitors (MGPCs) in an adult zebrafish model of mechanical retinal injury. Following a stab injury, the expression of Sox11b was induced in proliferating MGPCs in the retina. Sox11b knockdown did not affect MGPC formation at 4 days post-injury, although the nuclear morphology and subsequent radial migration of MGPCs were altered. At 7 days post-injury, Sox11b knockdown resulted in an increased proportion of MGPCs in the inner retina and a decreased proportion of MGPCs in the outer nuclear layer, compared with controls. Furthermore, Sox11b knockdown led to reduced photoreceptor regeneration, while it increased the numbers of newborn amacrines and retinal ganglion cells. Finally, quantitative polymerase chain reaction analysis revealed that Sox11b regulated the expression of Notch signaling components in the retina, and Notch inhibition partially recapitulated the Sox11b knockdown phenotype, indicating that Notch signaling functions downstream of Sox11b. Our findings imply that Sox11b plays key roles in MGPC migration and fate determination during retina regeneration in zebrafish, which may have critical implications for future explorations of retinal repair in mammals.

Two-Dimensional (PEA)2PbBr4 Perovskites Sensors for Highly Sensitive Ethanol Vapor Detection.

Two-dimensional (2D) perovskite have been widely researched for solar cells, light-emitting diodes, photodetectors because of their excellent environmental stability and optoelectronic properties in comparison to three-dimensional (3D) perovskite. In this study, we demonstrate the high response of 2D-(PEA)2PbBr4 perovskite of the horizontal vapor sensor was outstandingly more superior than 3D-MAPbBr3 perovskite. 2D transverse perovskite layer have the large surface-to-volume ratio and reactive surface, with the charge transfer mechanism, which was suitable for vapor sensing and trapping. Thus, 2D perovskite vapor sensors demonstrate the champion current response ratio R of 107.32 under the ethanol vapors, which was much faster than 3D perovskite (R = 2.92).

Context-dependent effects of inflammation on retina regeneration.

Inflammation is required for the proliferation of Müller glia (MG) into multipotent progenitors (MGPCs) in the injured fish and avian retinas. However, its function in retina regeneration has not been fully understood. Here we investigated the role of inflammation in three different retinal regeneration paradigms in zebrafish (stab-injury, NMDA-injury and insulin treatment). We first show that different types of immune cells and levels of inflammatory cytokines were found in the retinas of these paradigms. Though zymosan injection alone was insufficient to induce MG proliferation in the uninjured retina, immune suppression significantly inhibited MGPC formation in all three paradigms. Enhancing inflammation promoted MGPC formation after stab-injury, while exhibiting a context-dependent role in the NMDA or insulin models. We further show that proper levels of inflammation promoted MG reprogramming and cell cycle re-entry after stab- or NMDA-injury, but excessive inflammation also suppressed MG proliferation in the latter model. Finally, inflammation differentially affected neuronal regeneration in various injury paradigms. Our study reveals the complex and context-dependent role of inflammation during retinal repair in fish and suggests accurate inflammation management may be crucial for successful retina regeneration in mammals.

Realization of Curved Circular Nanotubes Using In Situ Monitored Self-Assembly.

Curved fluidic channels with a circular cross-section play an important role in biology, chemistry, and medicine. However, in nanofluidics, a problem that is largely unsolved is the lack of an effective fabrication method for curved circular nanotubes (10-1000 nm). In this work, an electron-beam-induced self-assembly process was applied to achieve fine curved nanostructures for the realization of nanofluidic devices. The diameter of the tube could be precisely controlled by an atomic layer deposition process. Fluid transported through the nanochannels was verified and characterized using a dark-field microscope under an optical diffraction limit size. The fluid flow demonstrates that the liquid's evaporation (vapor diffusion) in the nanochannel generates compressed vapor, which pumps the liquid and pushes it forward, resulting in a directional flow behavior in the ∼100 nm radius of tubes. This phenomenon could provide a useful platform for the development of diverse nanofluidic devices.

Magnetic Solid-Phase Extraction Based on Magnetic Sulfonated Reduced Graphene Oxide for HPLC-MS/MS Analysis of Illegal Basic Dyes in Foods.

In this study, a magnetic solid-phase extraction (MSPE) method coupled with High-Performance Liquid Chromatography Mass Spectrometry (HPLC-MS/MS) for the determination of illegal basic dyes in food samples was developed and validated. This method was based on Magnetic sulfonated reduced graphene oxide (M-S-RGO), which was sensitive and selective to analytes with structure of multiaromatic rings and negatively charged ions. Several factors affecting MSPE efficiency such as pH and adsorption time were optimized. Under the optimum conditions, the calibration curves exhibited good linearity, ranging from 5 to 60 µg/g with correlation coefficients >0.9950. The limits of detection of 16 basic dyes were in the range of 0.01-0.2 µg/L. The recoveries ranged from 70% to 110% with RSD% < 10%. The results indicate that M-S-RGO is an efficient and selective adsorbent for the extraction and cleanup of basic dyes. Due to the MSPE procedures, matrix effect and interference were eliminated in the analysis of HPLC-MS/MS without the matrix-matched standards. Thus, validation data showed that the proposed MSPE-HPLC-MS/MS method was rapid, efficient, selective, and sensitive for the determination of illegal basic dyes in foods.

Qualitative screening and quantitative determination of multiclass water-soluble synthetic dyes in foodstuffs by liquid chromatography coupled to quadrupole Orbitrap mass spectrometry.

A LC-Q-Orbitrap HRMS analytical method for both qualitative screening and quantitative determination of 90 synthetic dyes including ten groups of isomers in foods has been established. An in-house synthetic dyes database and characteristic ions were also developed. Based on Q-Orbitrap HRMS, mass spectrum and fragmentation patterns of synthetic dyes were studied, which indicated that double charged ions were usually the main precursor ions. Matrix effects were successfully eliminated by the C18 d-SPE clean-up coupled with dilute and shoot approach with methanol-water (1:4, v/v) in 100-fold. For most of the compounds, mean recoveries were satisfactory between 70% and 120% with RSD < 20% at three spiked level in the range of 0.025-1.0 mg/kg. The screening detection limits ranged from 0.025 - 1.0 mg/kg. Method validation showed that the established method was efficient, rapid and high-throughput, which has been successfully applied to the monitoring of these water-soluble synthetic dyes in foods.

CY-09 attenuates the progression of osteoarthritis via inhibiting NLRP3 inflammasome-mediated pyroptosis.

Excessive activation of inflammation in chondrocyte has been considered to be a major reason cause of cellular death and degeneration in osteoarthritis (OA) development. The NLRP3 inflammasome-mediated pyroptosis pathway is closely related to inflammation regulation. This research was conducted to confirm whether NLRP3 expression and activity are impacted in the development of OA and to detect the role of CY-09, a selective and direct inhibitor of NLRP3 in the in vitro and in vivo models of OA. Our findings corroborated that the expression of NLRP3 is stimulated in OA cartilage. CY-09 can maintain extracellular matrix (ECM) homeostasis and regulate inflammation in TNF-α treated chondrocytes via inhibition of NLRP3 inflammasome-mediated pyroptosis. Moreover, the chondrocyte protective effects of CY-09 were further confirmed in vivo in a DMM-induced OA model. In conclusion, our research indicates that experimental OA activated the NLRP3 activity, and pharmacological inhibition of NLRP3 inflammasome activation by CY-09 protects chondrocytes against inflammation and attenuates OA development.

Oroxylin A attenuates osteoarthritis progression by dual inhibition of cell inflammation and hypertrophy.

The imbalance between the anabolism and catabolism of the extracellular matrix (ECM) is of great importance to osteoarthritis (OA) development. Aberrant inflammatory responses and hypertrophic changes of chondrocytes are the main contributors to these metabolic disorders. In the present study, we found that Oroxylin A (ORA), a flavonoid compound derived from Oroxylum indicum, maintained ECM hemostasis of chondrocytes by Interleukin-1ß (IL-1ß) stimulation. Besides, it was demonstrated that IL-1ß induced over-production of inflammatory mediators was attenuated by ORA treatment. Moreover, ORA could rescue IL-1ß mediated hypertrophic alterations of chondrocytes. Mechanistically, ORA's protective effects were found to be associated with both NF-κB and Wnt/ß-catenin signaling inhibition. Meanwhile, molecular docking analysis revealed that ORA could strongly bind to the inhibitor kappa B kinaseß (IKKß) and dishevelled, Dsh Homolog 2 (Dvl2), the upstream molecules of the NF-κB axis and ß-catenin axis, respectively. In addition, ORA driven chondroprotective effects were also affirmed in a surgically induced OA mouse model. Taken together, the current study suggested that ORA might be a promising therapeutic option for the treatment of OA.

Self-Assembled 3D Nanosplit Rings for Plasmon-Enhanced Optofluidic Sensing.

Plasmonic sensors are commonly defined on two-dimensional (2D) surfaces with an enhanced electromagnetic field only near the surface, which requires precise positioning of the targeted molecules within hotspots. To address this challenge, we realize segmented nanocylinders that incorporate plasmonic (1-50 nm) gaps within three-dimensional (3D) nanostructures (nanocylinders) using electron irradiation triggered self-assembly. The 3D structures allow desired plasmonic patterns on their inner cylindrical walls forming the nanofluidic channels. The nanocylinders bridge nanoplasmonics and nanofluidics by achieving electromagnetic field enhancement and fluid confinement simultaneously. This hybrid system enables rapid diffusion of targeted species to the larger spatial hotspots in the 3D plasmonic structures, leading to enhanced interactions that contribute to a higher sensitivity. This concept has been demonstrated by characterizing an optical response of the 3D plasmonic nanostructures using surface-enhanced Raman spectroscopy (SERS), which shows enhancement over a 22 times higher intensity for hemoglobin fingerprints with nanocylinders compared to 2D nanostructures.

Simultaneous determination of multiclass illegal dyes with different acidic-basic properties in foodstuffs by LC-MS/MS via polarity switching mode.

Simultaneous determination of multiclass illegal dyes possessing different chemical properties is difficult. By using LC-MS/MS via negative/positive ion switching mode, an efficient and fast multi-residual method for simultaneous determination of multiclass 52 illegal dyes with different acidic-basic properties in foodstuffs was developed and validated during one single run, including 23 fat-soluble neutral azo dyes, 8 acidic sulfonated azo dyes, 12 triphenylmethane basic dyes, three basic indole dyes, three xanthene dyes, one quinoline dye, and two anthraquinones dyes. The illegal dyes were extracted with methanol-acetonitrile and further purified with d-SPE procedure to reduce interference. Sample dilution with 100-fold was used for the elimination of matrix effects of the quantitation of LC-MS/MS analysis. Validation data showed the good recoveries in the range of 71.2-111.2%, with relative standard deviations less than 20%, suggesting the developed method is suitable for the identification and quantitation of multiclass illegal dyes at trace levels in foods.

Tunable reflective color filters based on asymmetric Fabry-Perot cavities employing ultrathin Ge2Sb2Te5 as a broadband absorber.

We demonstrated a tunable structural color filter based on an asymmetric Fabry-Perot cavity employing germanium antimony tellurium alloy Ge2Sb2Te5 (GST) as a switchable ultrathin lossy layer. The color tunability and switch mechanism of our designed structure were investigated by both simulation and analytical approaches. Both numerical simulations and analytical results show that the tunable reflective colors can be generated through the reversible phase transition of GST from amorphous to crystalline. Additionally, the generated colors possess high brightness, high saturation, and a wide gamut. Our designed structure will inspire phase-transition-based systems' potential applications in colorimetric sensing, smart windows, full-color printing and displays, anti-counterfeiting, and data encryption.