Natural biomass-derived carbon dots as a potent solubilizer with high biocompatibility and enhanced antioxidant activity.

Numerous natural compounds exhibit low bioavailability due to suboptimal water solubility. The solubilization methods of the modern pharmaceutical industry in contemporary pharmaceutical research are restricted by low efficiency, sophisticated technological requirements, and latent adverse effects. There is a pressing need to elucidate and implement a novel solubilizer to ameliorate these challenges. This study identified natural biomass-derived carbon dots as a promising candidate. We report on natural fluorescent carbon dots derived from Aurantia Fructus Immatures (AFI-CDs), which have exhibited a remarkable solubilization effect, augmenting naringin (NA) solubility by a factor of 216.72. Subsequent analyses suggest that the solubilization mechanism is potentially contingent upon the oration of a nanostructured complex (NA-AFI-CDs) between AFI-CDs and NA, mediated by intermolecular non-covalent bonds. Concomitantly, the synthesized NA-AFI-CDs demonstrated high biocompatibility, exceptional stability, and dispersion. In addition, NA-AFI-CDs manifested superior free radical scavenging capacity. This research contributes foundational insights into the solubilization mechanism of naringin-utilizing AFI-CDs and proffers a novel strategy that circumvents the challenges associated with the low aqueous solubility of water-insoluble drugs in the field of modern pharmaceutical science.

Protective effect of carbon dots derived from scrambled Coptidis Rhizoma against ulcerative colitis in mice.

Introduction: Ulcerative colitis (UC) is a chronic and progressive inflammatory disease of the intestines. The primary symptoms, such as bloody diarrhea, can result in weight loss and significantly diminish the patient's quality of life. Despite considerable research endeavors, this disease remains incurable. The scrambled Coptidis Rhizoma (SCR) has a rich historical background in traditional Chinese medicine as a remedy for UC. Drawing from a wealth of substantial clinical practices, this study is focused on investigating the protective effects and underlying mechanisms of the active component of SCR, namely SCR-based carbon dots (SCR-CDs), in the treatment of UC. Methods: SCR-CDs were extracted and isolated from the decoction of SCR, followed by a comprehensive characterization of their morphological structure and functional groups. Subsequently, we investigated the effects of SCR-CDs on parameters such as colonic length, disease activity index, and histopathological architecture using the dextran sulfate sodium (DSS)-induced colitis mice model. Furthermore, we delved into the assessment of key aspects, including the expression of intestinal tight junction (TJ) proteins, inflammatory cytokines, oxidative stress markers, and gut microbial composition, to unravel the intricate mechanisms underpinning their therapeutic effects. Results: SCR-CDs displayed a consistent spherical morphology, featuring uniform dispersion and diameters ranging from 1.2 to 2.8 nm. These SCR-CDs also exhibited a diverse array of surface chemical functional groups. Importantly, the administration of SCR-CDs, particularly at higher dosage levels, exerted a noteworthy preventive influence on colonic shortening, elevation of the disease activity index and colonic tissue impairment caused by DSS. These observed effects may be closely associated with the hygroscopic capability and hemostatic bioactivity inherent to SCR-CDs. Concurrently, the application of SCR-CDs manifested an augmenting impact on the expression of intestinal TJ proteins, concomitantly leading to a significant reduction in inflammatory cell infiltration and amelioration of oxidative stress. Additionally, SCR-CDs treatment facilitated the restoration of perturbed gut microbial composition, potentially serving as a fundamental mechanism underlying their observed protective effects. Conclusion: This study demonstrates the significant therapeutic potential of SCR-CDs in UC and provides elucidation on some of their mechanisms. Furthermore, these findings hold paramount importance in guiding innovative drug discovery for anti-UC agents.

Anxiolytic effects of Chrysanthemum morifolium Ramat Carbonisata-based carbon dots in mCPP-induced anxiety-like behavior in mice: a nature-inspired approach.

Introduction: Anxiety disorders have emerged as a predominant health concern, yet existing pharmacological treatments for anxiety still present various challenges. Chrysanthemum morifolium Ramat Carbonisata (CMRC) has been utilized in China for approximately 400 years as a therapeutic intervention for anxiety disorders. In this study, a novel type of carbon dots derived from the decoction of Chrysanthemum morifolium Ramat Carbonisata (CMRC-CDs) was identified and isolated, and their morphological structure and functional groups were characterized. Furthermore, the effects of CMRC-CDs on m-chlorophenylpiperazine (mCPP)-induced anxiety-like behaviour in mice were examined and quantified. In order to investigate the potential mechanisms of their anxiolytic effects, concentrations of hypothalamic-pituitary-adrenal (HPA) axis hormones, amino acid neurotransmitters, and monoamine neurotransmitters were measured. Methods: In this study, we synthesized CMRC-CDs and evaluated their potential anti-anxiety effects in a controlled experiment involving 48 male ICR mice. The mice were randomly divided into six groups, treated with CMRC-CDs at different doses for 14 days, and subjected to Open-Field (OF) and Elevated Plus Maze (EPM) tests. Post-behavioral evaluations, blood samples and brain tissues were collected for neurotransmitter and Hypothalamic-Pituitary-Adrenal (HPA) axis hormone quantification via ELISA. Additionally, cytotoxicity of CMRC-CDs was assessed using a Cell Counting Kit-8 (CCK-8) assay on RAW 264.7 cells. Results and Discussion: CMRC-CDs were spherical and homogeneously dispersed, with diameters ranging from 1.4 to 4.0 nm and an abundance of chemical groups on their surface. In the open-field (OF) test, mice pre-treated with CMRC-CDs demonstrated an increased proportion of time spent in the central area and a higher frequency of entries into the central area. In the elevated plus maze (EPM) test, mice pre-treated with CMRC-CDs exhibited a greater number of entries into the open arm and an extended duration spent in the open arm. CMRC-CDs were observed to decrease serum concentrations of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT). Furthermore, CMRC-CDs were found to increase γ-aminobutyric acid (GABA) and 5-hydroxytryptamine (5-HT) levels, while concurrently reducing glutamic acid (Glu) concentrations in brain tissue. CMRC-CDs demonstrated anxiolytic effects, which may be attributed to their modulation of hormones and neurotransmitters. This finding suggests the potential therapeutic value of CMRC-CDs in the clinical treatment of anxiety disorders.

Aurantii fructus immaturus carbonisata-derived carbon dots and their anti-depression effect.

Introduction: Depression is a common illness worldwide. However, the current treatments available for depression only achieve relative success, often come with several side effects, and are associated with high costs. Aurantii Fructus Immaturus (AFI) has a rich historical legacy in Traditional Chinese Medicine (TCM) for its traditional use as a treatment for depression. In this research, our primary objective is to examine the potential antidepressant properties and the mechanisms at play behind a particular bioactive compound found in AFI, which is referred to as carbon dots derived from AFI Carbonisata (AFIC-CDs). Methods: Extracted and isolated the AFIC-CDs from the decoction of AFIC, then characterized the morphological structure and functional groups comprehensively. We then utilized two distinct models to investigate the anti-depressive properties of AFIC-CDs: the chronic unpredictable mild stress (CUMS) model and the reserpine-induced pain-depression dyad model. In the CUMS model, we assessed immobile time and measured neurotransmitter levels in the mouse brain cortex. In the pain-depression dyad model, we evaluated immobile time, neurotransmitter levels, interleukin-1 (IL-1ß) and tumor necrosis factor-α (TNF-α) levels, and the expression of mRNA of brain-derived neurotrophic factor (BDNF) and tryptophan hydroxylase 2 (Tph2). Results: AFIC-CDs were found to have abundant chemical groups, and their diameter ranged from 2 to 10 nm. In the CUMS model, AFIC-CDs demonstrated significant effects. They reduced the immobile time of the mice and increased the levels of serotonin (5-HT), dopamine (DA), and norepinephrine (NE) in the mouse brain cortex. In the pain-depression dyad model, the AFIC-CDs groups decreased the immobile time, showed effect in increasing both the neurotransmitters' levels and the expression of mRNA of BDNF and Tph2, and decreased the IL-1ß and TNF-α levels in mouse brain cortex. Taken together, these results strongly indicate that AFIC-CDs possess significant antidepressant activity. Conclusion: AFIC-CDs demonstrate promising therapeutic potential in the treatment of depression, suggesting that they may become a valuable candidate for depression management. This not only extends the understanding of the biological activity of carbon dots (CDs) but also opens up new possibilities for the development of effective depression treatment strategies.

Neuroregenerative gene therapy to treat temporal lobe epilepsy in a rat model.

Temporal lobe epilepsy (TLE) is a common drug-resistant epilepsy associated with abundant cell death in the hippocampus. Here, we develop a novel gene therapy-mediated cell therapy that regenerates GABAergic neurons using internal hippocampal astrocytes to suppress seizure activity in a rat TLE model. We discovered that TLE-induced reactive astrocytes in the hippocampal CA1 region can be efficiently converted into GABAergic neurons after overexpressing a neural transcription factor NeuroD1. The astrocyte-converted neurons showed typical markers of GABAergic interneurons, fired action potentials, and formed functional synaptic connections with other neurons. Following NeuroD1-mediated astrocyte-to-neuron conversion, the number of hippocampal interneurons was significantly increased, and the spontaneous recurrent seizure (SRS) activity was significantly decreased. Moreover, NeuroD1 gene therapy treatment rescued total neuronal loss in the CA1 region and ameliorated the cognitive and mood dysfunctions in the TLE rat model. These results suggest that regeneration of GABAergic interneurons through gene therapy approach may provide a novel therapeutic intervention to treat drug-resistant TLE.

Metformin inhibits MAPK signaling and rescues pancreatic aquaporin 7 expression to induce insulin secretion in type 2 diabetes mellitus.

Metformin is the first-line antidiabetic agent for type 2 diabetes mellitus (T2DM) treatment. Although accumulated evidence has shed light on the consequences of metformin action, the precise mechanisms of its action, especially in the pancreas, are not fully understood. Aquaporin 7 (AQP7) acts as a critical regulator of intraislet glycerol content, which is necessary for insulin production and secretion. The aim of this study was to investigate the effects of different doses of metformin on AQP7 expression and explore the possible mechanism of its protective effects in the pancreatic islets. We used an in vivo model of high-fat diet in streptozocin-induced diabetic rats and an in vitro model of rat pancreatic ß-cells (INS-1 cells) damaged by hyperglycemia and hyperlipidemia. Our data showed that AQP7 expression levels were decreased, whereas p38 and JNK mitogen-activated protein kinases (MAPKs) were activated in vivo and in vitro in response to hyperglycemia and hyperlipidemia. T2DM rats treated with metformin demonstrated a reduction in blood glucose levels and increased regeneration of pancreatic ß-cells. In addition, metformin upregulated AQP7 expression as well as inhibited activation of p38 and JNK MAPKs both in vivo and in vitro. Overexpression of AQP7 increased glycerol influx into INS-1 cells, whereas inhibition of AQP7 reduced glycerol influx, thereby decreasing subsequent insulin secretion. Our findings demonstrate a new mechanism by which metformin suppresses the p38 and JNK pathways, thereby upregulating pancreatic AQP7 expression and promoting glycerol influx into pancreatic ß-cells and subsequent insulin secretion in T2DM.

Facile one-step photolithographic method for engineering hierarchically nano/microstructured transparent superamphiphobic surfaces.

It is of great value to develop a simple, controllable, and scalable method of making superamphiphobic surfaces. Here we present a facile one-step photolithographic method to engineer superamphiphobic surfaces consisting of photoresist micropillars decorated with nanoparticles of the same photoresist. The surface or coating is optically transparent and versatile, and can be fabricated on a broad range of substrates including stretchable elastomers. During the development of the micropillar array, photoresist nanoparticles are spontaneously grown on the micropillars by a well-controlled emulsification process of the un-cross-linked residual photoresist. This creates a hierarchical structure with a re-entrant and convex morphology which is the key for superoleophobicity. The chemical bonding between the nanoparticles and the micropillars is strong producing a robust and durable coating. This facile method is scalable and industry-applicable for a variety of applications such as self-cleaning, antifouling, and deicing/antifrosting.

Optimization of gold nanoring arrays for biosensing in the fiber-optic communication window.

To improve the limit of detection in a nanoplasmonic sensor system, the optical performance of the metal nanostructures should be optimized according to the best spectral window of the measurement instrument. We propose that the spectral window from 1460 to 1610 nm can potentially provide ultrahigh instrumental resolution for biosensing. We optimized gold nanoring arrays such that the extinction peak position is inside the proposed window, the extinction peak is sharp enough to track the peak shift with high resolution and the figure of merit (sensitivity/linewidth) of the array is optimized at the same time. The peak-sharpening effect of the array caused by coherent interaction plays a central role in the optimization. The optimized array has a lattice constant in the range [1000 nm,1060 nm], a bulk index sensitivity of around 450 nm/RIU and a figure of merit larger than 4. It is an enabling sensor element for a near-infrared sensor chip with ultrahigh resolution.

An electrochemical Lab-on-a-CD system for parallel whole blood analysis.

Lab-on-a-CD, as a main branch of Lab-on-a-chip technology, has led to several very successful commercial products. Most of these existing Lab-on-a-CD systems present complex system designs and thus are relatively expensive. In this work, we have developed a simple but robust Lab-on-a-CD system for parallel whole blood analyses. This Lab-on-a-CD system incorporates electrochemical bioanalysis and a simple blood sample separation mechanism into the centrifugal platform, and thus reduces the system's complexity. To demonstrate the applicability, the system was applied to perform basic metabolic panel tests, for example, the concentrations of glucose, lactate and uric acids of whole blood samples. Using only 16 µL of whole blood, within a few minutes, the Lab-on-a-CD system could produce results that agreed in general with the data by a conventional system. Therefore, this proof-of-concept Lab-on-a-CD system has demonstrated the potential to become a robust and simple-to-use device for parallel blood analyses.

Fabrication of nanoporous thin-film working electrodes and their biosensing applications.

Electrochemical detection for point-of-care diagnostics is of great interest due to its high sensitivity, fast analysis time and ability to operate on a small scale. Herein, we report the fabrication of a nanoporous thin-film electrode and its application in the configuration of a simple and robust enzymatic biosensor. The nanoporous thin-film was formed in a planar gold electrode through an alloying/dealloying process. The nanoporous electrode has an electroactive surface area up to 40 times higher than that of a flat gold electrode of the same size. The nanoporous electrode was used as a substrate to build an enzymatic electrochemical biosensor for the detection of glucose in standard samples and control serum samples. The example glucose biosensor has a linear response up to 30 mM, with a high sensitivity of 0.50 µA mM⁻¹ mm⁻², and excellent anti-interference ability against lactate, uric acid and ascorbic acid. Abundant catalyst and enzyme were stably entrapped in the nanoporous structure, leading to high stability and reproducibility of the biosensor. Development of such nanoporous structure enables the miniaturization of high-performance electrochemical biosensors for point-of-care diagnostics or environmental field testing.