Fluorescence nanoprobes bearing low temperature-derived biochar nanoparticles as efficient quenchers for the detection of single-stranded DNA and 17ß-estradiol and their analytical potential.

Bagasse-derived biochar nanoparticles obtained under a low pyrolysis condition (400 °C) were first revealed to be capable of highly efficiently quenching the fluorescence of 6-carboxyfluorescein, with a significantly improved quenching rate constant over that of other quenchers and high-temperature prepared ones, and were designated as bagasse-derived quencher nanoparticles (BQNPs). The BQNPs are suitable for the construction of fluorescence nanoprobes, taking advantage of their various beneficial properties, including low cost, environmental friendliness, high dispersibility, and rich functional groups that allow their easy and versatile molecular modification. They were demonstrated to be capable of stably binding single-stranded oligonucleotides through both adsorption and covalent interactions and were utilized for the construction of both BQNPs/DNA and BQNPs/aptamer probes. The BQNPs/DNA probe had strong resistance against degradation by deoxyribonuclease I and showed high precision and selectivity for the detection of single-stranded DNA, with a limit of detection of 1.04 nM. Moreover, the BQNPs/aptamer probe demonstrated the rapid and sensitive detection of 17ß-estradiol (E2) with a limit of detection of 0.4 ng mL-1 with no cross-reactivity with the analogues, and it was also applied for real environmental sample detection and demonstrated reasonable signal recoveries. Benefiting from their strong quenching ability, low cost, and great dispersibility, the BQNPs show great potential for the development of cost-effective and sensitive fluorescence sensors.

Ion-Selective Transport Promotion Enabled by Angstrom-Scale Nanochannels in Dendrimer-Assembled Polyamide Nanofilm for Efficient Electrodialysis.

The ion permeability and selectivity of membranes are crucial in nanofluidic behavior, impacting industries ranging from traditional to advanced manufacturing. Herein, we demonstrate the engineering of ion-conductive membranes featuring angstrom-scale ion-transport channels by introducing ionic polyamidoamine (PAMAM) dendrimers for ion separation. The exterior quaternary ammonium-rich structure contributes to significant electrostatic charge exclusion due to enhanced local charge density; the interior protoplasmic channels of PAMAM dendrimer are assembled to provide additional degrees of free volume. This facilitates the monovalent ion transfer while maintaining continuity and efficient ion screening. The dendrimer-assembled hybrid membrane achieves high monovalent ion permeance of 2.81 mol m-2 h-1 (K+), reaching excellent mono/multivalent selectivity up to 20.1 (K+/Mg2+) and surpassing the permselectivities of state-of-the-art membranes. Both experimental results and simulating calculations suggest that the impressive ion selectivity arises from the significant disparity in transport energy barrier between mono/multivalent ions, induced by the "exterior-interior" synergistic effects of bifunctional membrane channels.

DNA demethylase Tet2 promotes the terminal maturation of natural killer cells.

The cytotoxicity feature to eliminate malignant cells makes natural killer (NK) cells a candidate for tumor immunotherapy. However, this scenario is currently hampered by inadequate understanding of the regulatory mechanisms of NK cell development. Ten-Eleven-Translocation 2 (Tet2) is a demethylase whose mutation was recently shown to cause phenotypic defects in NK cells. However, the role of Tet2 in the development and maturation of NK cells is not entirely clear. Here we studied the modulatory role of Tet2 in NK cell development and maturation by generating hematopoietic Tet2 knockout mice and mice with Tet2 conditional deletion in NKp46+ NK cells. The results showed that both hematopoietic and NK cell conditional deletion of Tet2 had no effect on the early steps of NK cell development, but impaired the terminal maturation of NK cells defined by CD11b, CD43, and KLRG1 expression. In the liver, Tet2 deletion not only prevented the terminal maturation of NK cells, but also increased the proportion of type 1 innate lymphoid cells (ILC1s) and reduced the proportion of conventional NK cells (cNK). Moreover, hematopoietic deletion of Tet2 lowered the protein levels of perforin in NK cells. Furthermore, hematopoietic deletion of Tet2 downregulated the protein levels of Eomesodermin (Eomes), but not T-bet, in NK cells. In conclusion, our results demonstrate that Tet2 plays an important role in the terminal maturation of NK cells, and the Eomes transcription factor may be involved.

Weighted Mostar invariants of chemical compounds: An analysis of structural stability.

The concept of the weighted Mostar invariant is a mathematical tool used in chemical graph theory to study the stability of chemical compounds. Several recent studies have explored the weighted Mostar invariant of various chemical structures, including hydrocarbons, alcohols, and other organic compounds. One of the key advantages of the weighted Mostar invariant is that it can be easily computed for large and complex chemical structures, making it a valuable tool for studying the stability of a wide range of chemical compounds. This notion has been utilized to build novel approaches for forecasting chemical compound stability, such as machine learning algorithms. The focus of the paper is to demonstrate the weighted Mostar indices of three specific nanostructures: silicon dioxide (SIO2, poly-methyl methacrylate network (PMMA(s)), and melem chains (MC(h)). The authors seek to provide the findings of their investigation of these nanostructures using the weighted Mostar invariant.

Elevation-associated pathways mediate aquatic biodiversity at multi-trophic levels along a plateau inland river.

Aquatic biodiversity plays a significant role in maintaining the ecological balance and the overall health of riverine ecosystems. Elevation is an important factor influencing biodiversity patterns. However, it is still unclear through which pathway elevation influences riverine biodiversity at different trophic levels. In this study, the elevation-associated pathways affecting aquatic biodiversity at different trophic levels were explored using structural equation modeling (SEM) and taking the Bayin River, China as the case. The results showed that the elevational patterns were different among aquatic organisms at different trophic levels. For macroinvertebrates and bacteria, the pattern was hump-shaped; while for phytoplankton and zooplankton, it was U-shaped. Building upon these observed elevational patterns, our investigation delved into the direct and indirect pathways through which elevation influences aquatic biodiversity. We found that elevation exerts an impact on aquatic biodiversity via indirect pathways. For all aquatic organisms investigated, the major pathway through which elevation influences biodiversity is mediated by water temperature and water quality. For aquatic organisms at higher trophic levels, like macroinvertebrates and zooplankton, the crucial pathway is also mediated by the landscape. The results of this study contributed to understanding the effects of elevation on aquatic organisms at different trophic levels and provided an important basis for the assessment of riverine biodiversity at large scales.

Harnessing Graphdiyne for Selective Cu2+ Detection: A Promising Tool for Parkinson's Disease Diagnostics and Pathogenesis.

Cu2+ accelerates the viral-like propagation of α-synuclein fibrils and plays a key role in the pathogenesis of Parkinson's disease (PD). Therefore, the accurate detection of Cu2+ is essential for the diagnosis of PD and other neurological diseases. The Cu2+ detection process is impeded by substances that have similar electrochemical properties. In this study, graphdiyne (GDY), a new kind of carbon allotrope with strong electron-donating ability, was utilized for the highly selective detection of Cu2+ by taking advantage of its outstanding adsorption capacity for Cu2+. Density functional theory (DFT) calculations show that Cu atoms are adsorbed in the cavity of GDY, and the absorption energy between Cu and C atoms is higher than that of graphene (GR), indicating that the cavity of GDY is favorable for the adsorption of Cu atoms and electrochemical sensing. The GDY-based electrochemical sensor can effectively avoid the interference of amino acids, metal ions and neurotransmitters and has a high sensitivity of 9.77 µA·µM-1·cm-2, with a minimum detectable concentration of 200 nM. During the investigating pathogenesis and therapeutic process of PD with α-synuclein as the diagnostic standard, the concentration of Cu2+ in cells before and after L-DOPA and GSH treatments were examined, and it was found that Cu2+ exhibits high potential as a biomarker for PD. This study not only harnesses the favorable adsorption of the GDY and Cu2+ to improve the specificity of ion detection but also provide clues for deeper understanding of the role of Cu2+ in neurobiology and neurological diseases.

mTOR Signaling Promotes Rapid m6A mRNA Methylation to Regulate NK-Cell Activation and Effector Functions.

NK cells can be rapidly activated in response to cytokines during host defense against malignant cells or viral infection. However, it remains unclear what mechanisms precisely and rapidly regulate the expression of a large number of genes involved in activating NK cells. In this study, we discovered that NK-cell N6-methyladenosine (m6A) methylation levels were rapidly upregulated upon short-term NK-cell activation and were repressed in the tumor microenvironment (TME). Deficiency of methyltransferase-like 3 (METTL3) or METTL14 moderately influenced NK-cell homeostasis, while double-knockout of METTL3/14 more significantly impacted NK-cell homeostasis, maturation, and antitumor immunity. This suggests a cooperative role of METTL3 and METTL14 in regulating NK-cell development and effector functions. Using methylated RNA immunoprecipitation sequencing, we demonstrated that genes involved in NK-cell effector functions, such as Prf1 and Gzmb, were directly modified by m6A methylation. Furthermore, inhibiting mTOR complex 1 activation prevented m6A methylation levels from increasing when NK cells were activated, and this could be restored by S-adenosylmethionine supplementation. Collectively, we have unraveled crucial roles for rapid m6A mRNA methylation downstream of the mTOR complex 1-S-adenosylmethionine signal axis in regulating NK-cell activation and effector functions.

Superoxide dismutase nanozymes: current status and future perspectives on brain disease treatment and diagnosis.

Superoxide dismutase (SOD) is an important metalloenzyme that catalyzes the dismutation of superoxide radicals (O2˙-) into hydrogen peroxide (H2O2) and oxygen (O2). However, the clinical application of SOD is severely limited due to its structural instability and high cost. Compared with natural enzymes, nanomaterials with enzyme-like activity, nanoenzymes, are more stable, economical and easy to modify and their activity can be adjusted. Certain nanozymes that exhibit SOD-like activity have been created and shown to help prevent illnesses brought about by oxidative stress. These SOD-like nanozymes offer an important solution to the problems associated with the clinical application of SOD. In this review, we briefly introduce neurodegenerative diseases, present the research progress of SOD-like nanoenzymes in the diagnosis and treatment of brain diseases, review their mechanism of action in the treatment and diagnosis of brain diseases, and discuss the shortcomings of the current research with a view to providing a reference for future research. We expect more highly active SOD-like nanoenzymes to be developed with a wide range of applications in the diagnosis and treatment of brain diseases.

Nano La(OH)3 modified lotus seedpod biochar: A novel solution for effective phosphorus removal from wastewater.

Effective removal of phosphorus from water is crucial for controlling eutrophication. Meanwhile, the post-disposal of wetland plants is also an urgent problem that needs to be solved. In this study, seedpods of the common wetland plant lotus were used as a new raw material to prepare biochar, which were further modified by loading nano La(OH)3 particles (LBC-La). The adsorption performance of the modified biochar for phosphate was evaluated through batch adsorption and column adsorption experiments. Adsorption performance of lotus seedpod biochar was significantly improved by La(OH)3 modification, with adsorption equilibrium time shortened from 24 to 4 h and a theoretical maximum adsorption capacity increased from 19.43 to 52.23 mg/g. Moreover, LBC-La maintained a removal rate above 99% for phosphate solutions with concentrations below 20 mg/L. The LBC-La exhibited strong anti-interference ability in pH (3-9) and coexisting ion experiments, with the removal ratio remaining above 99%. The characterization analysis indicated that the main mechanism is the formation of monodentate or bidentate lanthanum phosphate complexes through inner sphere complexation. Electrostatic adsorption and ligand exchange are also the mechanisms of LBC-La adsorption of phosphate. In the dynamic adsorption experiment of simulated wastewater treatment plant effluent, the breakthrough point of the adsorption column was 1620 min, reaching exhaustion point at 6480 min, with a theoretical phosphorus saturation adsorption capacity of 6050 mg/kg. The process was well described by the Thomas and Yoon-Nelson models, which indicated that this is a surface adsorption process, without the internal participation of the adsorbent.

A cross-sectional study of the relationship between premenstrual syndrome and missed nursing care among female nursing staff.

Purpose: Premenstrual syndrome (PMS) is a cyclical psychosomatic disorder prevalent among women of reproductive age. However, research on the potential impact of PMS on routine nursing schedules and activities is limited. This study aims to identify the prevalence of PMS among female nursing staff and to examine the relationship between PMS and missed nursing care (MNC). Method: Between November 1, 2022, and April 30, 2023, this study was conducted among female nursing staff working in nine inpatient departments at Sun Yat-sen University Cancer Center. This study used a cross-sectional design. The participants were recruited through convenience sampling. Data were collected using the standardized Menstrual Distress Questionnaire, the Oncology Missed Nursing Care self-rating scale, and a sociodemographic questionnaire. One-way analysis of variance, Fisher's least significant difference test for post-hoc comparisons, and Spearman's correlation coefficient were utilized for data analysis. A trend test was also performed to explore patterns in the severity of PMS and MNC over time. Results: We collected a total of 224 questionnaires, with 154 (68.7%) female nursing staff reporting PMS. The most common symptoms were low back pain (91.1%), abdominal discomfort (90.6%), cold hands and feet (87.1%), and lethargy (87.1%). Moreover, 91.5% of the 224 female nursing staff reported at least one MNC activity. The nursing activities most frequently missed or left incomplete were liquid intake and output monitoring as ordered (43.3%), medication administration within 30 min before or after the scheduled time (43.3%), and electrocardiogram monitoring as ordered (42.9%). "Abdominal discomfort" from the Menstrual Distress Questionnaire was significantly correlated with the majority of MNC activities (p < 0.001). Conclusions: This study provides evidence for a strong association between PMS and MNC among female nursing staff, suggesting that administrators should take the premenstrual conditions of female nursing staff into consideration. It is necessary to provide appropriate understanding and support to mitigate the impact on patient care and safety.

Selection and Validation of qRT-PCR Internal Reference Genes to Study Flower Color Formation in Camellia impressinervis.

Real-time quantitative PCR (qRT-PCR) is a pivotal technique for gene expression analysis. To ensure reliable and accurate results, the internal reference genes must exhibit stable expression across varied experimental conditions. Currently, no internal reference genes for Camellia impressinervis have been established. This study aimed to identify stable internal reference genes from eight candidates derived from different developmental stages of C. impressinervis flowers. We employed geNorm, NormFinder, and BestKeeper to evaluate the expression stability of these candidates, which was followed by a comprehensive stability analysis. The results indicated that CiTUB, a tubulin gene, exhibited the most stable expression among the eight reference gene candidates in the petals. Subsequently, CiTUB was utilized as an internal reference for the qRT-PCR analysis of six genes implicated in the petal pigment synthesis pathway of C. impressinervis. The qRT-PCR results were corroborated by transcriptome sequencing data, affirming the stability and suitability of CiTUB as a reference gene. This study marks the first identification of stable internal reference genes within the entire genome of C. impressinervis, establishing a foundation for future gene expression and functional studies. Identifying such stable reference genes is crucial for advancing molecular research on C. impressinervis.

Nanomaterials Regulate Bacterial Quorum Sensing: Applications, Mechanisms, and Optimization Strategies.

Anti-virulence therapy that interferes with bacterial communication, known as "quorum sensing (QS)", is a promising strategy for circumventing bacterial resistance. Using nanomaterials to regulate bacterial QS in anti-virulence therapy has attracted much attention, which is mainly attributed to unique physicochemical properties and excellent designability of nanomaterials. However, bacterial QS is a dynamic and multistep process, and there are significant differences in the specific regulatory mechanisms and related influencing factors of nanomaterials in different steps of the QS process. An in-depth understanding of the specific regulatory mechanisms and related influencing factors of nanomaterials in each step can significantly optimize QS regulatory activity and enhance the development of novel nanomaterials with better comprehensive performance. Therefore, this review focuses on the mechanisms by which nanomaterials regulate bacterial QS in the signal supply (including signal synthesis, secretion, and accumulation) and signal transduction cascade (including signal perception and response) processes. Moreover, based on the two key influencing factors (i.e., the nanomaterial itself and the environment), optimization strategies to enhance the QS regulatory activity are comprehensively summarized. Collectively, applying nanomaterials to regulate bacterial QS is a promising strategy for anti-virulence therapy. This review provides reference and inspiration for further research on the anti-virulence application of nanomaterials.

Design, synthesis and evaluation of C-5 substituted pyrrolopyridine derivatives as potent Janus Kinase 1 inhibitors with excellent selectivity.

The development of highly selective Janus Kinase 1 (JAK1) inhibitors is crucial for improving efficacy and minimizing adverse effects in the clinical treatment of autoimmune diseases. In a prior study, we designed a series of C-5 4-pyrazol substituted pyrrolopyridine derivatives that demonstrated significant potency against JAK1, with a 10 âˆ¼ 20-fold selectivity over Janus Kinase 2 (JAK2). Building on this foundation, we adopted orthogonal strategy by modifying the C-5 position with 3-pyrazol/4-pyrazol/3-pyrrol groups and tail with substituted benzyl groups on the pyrrolopyridine head to enhance both potency and selectivity. In this endeavor, we have identified several compounds that exhibit excellent potency and selectivity for JAK1. Notably, compounds 12b and 12e, which combined 4-pyrazol group at C-5 site and meta-substituted benzyl tails, displayed IC50 value with 2.4/2.2 nM and high 352-/253-fold selectivity for JAK1 over JAK2 in enzyme assays. Additionally, both compounds showed good JAK1-selective in Ba/F3-TEL-JAK1/2 cell-based assays. These findings mark a substantial improvement, as these compounds are 10-fold more potent and over 10-fold more selective than the best compound identified in our previous study. The noteworthy potency and selectivity properties of compounds 12b and 12e suggest their potential utility in furthering the development of drugs for autoimmune diseases.

Does a hydropower reservoir cascade really harm downstream nutrient regimes.

River damming is believed to largely intercept nutrients, particularly retain more phosphorus (P) than nitrogen (N), and thus harm primary productivity, fishery catches, and food security downstream, which seriously constrain global hydropower development and poverty relief in undeveloped regions and can drive geo-political disputes between nations along trans-boundary rivers. In this study, we investigated whether reservoirs can instead improve nutrient regimes downstream. We measured different species of N and P as well as microbial functions in water and sediment of cascade reservoirs in the upper Mekong River over 5 years and modelled the influx and outflux of N and P species in each reservoir. Despite partially retaining total N and total P, reservoirs increased the downstream flux of ammonium and soluble reactive phosphorus (SRP). The increase in ammonium and SRP between outflux and influx showed positive linear relationships with the hydraulic residence time of the cascade reservoirs; and the ratio of SRP to dissolved inorganic nitrogen increased along the reservoir cascade. The lentic environment of reservoirs stimulated algae-mediated conversion of nitrate into ammonium in surface water; the hypoxic condition and the priming effect of algae-induced organic matter enhanced release of ammonium from sediment; the synergy of microbial phosphorylation, reductive condition and sediment geochemical properties increased release of SRP. This study is the first to provide solid evidence that hydropower reservoirs improve downstream nutrient bioavailability and N-P balance through a process of retention-transformation-transport, which may benefit primary productivity. These findings could advance our understanding of the eco-environmental impacts of river damming.

Antioxidant response to ZnO nanoparticles in juvenile Takifugu obscurus: protective effects of salinity.

The extensive utilization of Zinc Oxide nanoparticles (ZnO NPs) has garnered significant attention due to their detrimental impacts on ecosystem. Unfortunately, ecotoxicity of ZnO NPs in coastal waters with fluctuating salinity has been disregarded. This study mainly discussed the toxic effects of ZnO NPs on species inhabiting the transition zones between freshwater and brackish water, who are of great ecological and economic importance among fish. To serve as the model organism, Takifugu obscurus, a juvenile euryhaline fish, was exposed to different ZnO NPs concentrations (0-200 mg/L) and salinity levels (0 and 15 ppt). The results showed that a moderate increase in salinity (15 ppt) could alleviate the toxic effect of ZnO NPs, as evidenced by improved survival rates. The integrated biomarker response index on oxidative stress also revealed that the toxicity of ZnO NPs was higher in freshwater compared to brackish water. These outcomes can be attributed to higher salinity (15 ppt) reducing the bioavailability of ZnO NPs by facilitating their aggregation and inhibiting the release of metal ions. It is noteworthy that elevated salinity was found to alleviate ZnO NPs toxicity by means of osmotic adjustment via the activation of Na+/K+-ATPase activity. This study demonstrates the salinity-dependent effect of ZnO NPs on T. obscurus, suggesting the possibility for euryhaline fish like T. obscurus to adapt their habitat towards more saline environments, under constant exposure to ZnO NPs.

Chemically Tailored Single Atoms for Targeted and Light-Controlled Bactericidal Activity.

Single-atom (SA) nanoparticles exhibit considerable potential in terms of photothermal properties for bactericidal applications. Nevertheless, the restricted efficacy of their targeted and controlled antibacterial activity has hindered their practical implementation. This study aims to overcome this obstacle by employing chemical modifications to tailor SAs, thereby achieving targeted and light-controlled antimicrobial effects. By conducting atomic-level modifications on palladium SAs using glutathione (GSH) and mercaptophenylboronic acid (MBA), their superior targeted binding capabilities toward Escherichia coli cells are demonstrated, surpassing those of SAs modified with cysteine (Cys). Moreover, these modified SAs effectively inhibit wound bacteria proliferation and promote wound healing in rats, without inducing noticeable toxicity to major organs under 808 nm laser irradiation. This study highlights the significance of chemical engineering in tailoring the antibacterial properties of SA nanoparticles, opening avenues for combating bacterial infections and advancing nanoparticle-based therapies.

Higher matrix stiffness promotes VSMC senescence by affecting mitochondria-ER contact sites and mitochondria/ER dysfunction.

Abdominal aortic aneurysm (AAA) is a prevalent condition characterized by the weakening and bulging of the abdominal aorta. This study aimed to investigate the impact of a stiff matrix on vascular smooth muscle cells (VSMCs) in AAA development. Bioinformatics analysis revealed that differentially expressed genes (DEGs) in VSMCs of an AAA mouse model were enriched in cellular senescence and related pathways. To simulate aging-related changes, VSMCs were cultured on stiff matrices, and compared to those on soft matrices, the VSMCs cultured on stiff matrices exhibited cellular senescence. Furthermore, the mutual distance between mitochondria and endoplasmic reticulum (ER) in VSMCs was increased, indicating altered mitochondria-endoplasmic reticulum contacts (MERCs). The observed upregulation of reactive oxygen species (ROS) levels, antioxidant gene expression, and decreased mitochondrial membrane potential suggested the presence of mitochondrial dysfunction in VSMCs cultured on a stiff matrix. Additionally, the induction of ER stress-related genes indicated ER dysfunction. These findings collectively indicated impaired functionality of both mitochondria and ER in VSMCs cultured on a stiff matrix. Moreover, our data revealed that high lipid levels exacerbated the effects of high matrix stiffness on VSMCs senescence, MERC sites, and mitochondria/ER dysfunction. Importantly, treatment with the antilipemic agent CI-981 effectively reversed these detrimental effects. These findings provide insights into the role of matrix stiffness, mitochondrial dysfunction, ER stress, and lipid metabolism in AAA development, suggesting potential therapeutic targets for intervention.

Cu single-atom catalyst-based flexible hydrogen peroxide electrochemical sensor with oxygen resistance for monitoring ROS bursts.

The study of cellular responses linked to oxidative stress mechanisms is crucial in comprehending diverse physiological and pathological life processes, including mitochondrial dysfunction. Nonetheless, despite the interference of O2, the monitoring of ROS released from cells poses a challenging task. In this study, carbon-based copper single-atom catalysts (Cu SACs) were synthesized that exhibits excellent electrocatalytic performance for H2O2 reduction with an initial potential at 0.23 V and effectively avoids interference from O2. Based on this catalyst, a flexible and stretchable oxygen-tolerant sensor was constructed and applied to monitor the calcium ion-induced ROS burst in human umbilical vein endothelial cells (HUVECs) in a simulated physiological condition. This study effectively eradicates interference that may arise from the reduction of O2 and presents a dependable platform for real-time in situ monitoring of physiologically active molecules by utilizing H2O2 detection.

Overexpression of miR-297b-5p in Mouse Insulin-Secreting Cells Promotes Metformin-Mediated Protection Against Stearic Acid-Induced Senescence by Targeting Igf1r.

BACKGROUND: A long-term consumption of saturated fat significantly increases the concentration of saturated fatty acids in serum, which accelerates the appearance of senescence markers in ß-cells and leads to their dysfunction. An understanding of the mechanisms underlying ß-cell senescence induced by stearic acid and the exploration of effective agents preventing it remains largely unclear. Here, we aimed to investigate the protective effect of metformin against stearic acid-treated ß-cell senescence and to assess the involvement of miR-297b-5p in this process. METHODS: To identify senescence, we measured senescence-associated ß-galactosidase activity and the expression of senescence-related genes. Gain and loss of function approaches were applied to explore the role of miR-297b-5p in stearic acid-induced ß-cell senescence. Bioinformatics analysis and a luciferase activity assay were used to predict the downstream targets of miR-297b-5p. RESULTS: Stearic acid markedly induced senescence and suppressed miR-297b-5p expression in mouse ß-TC6 cells, which were significantly alleviated by metformin. After transfection of miR-297b-5p mimics, stearic acid-evoked ß-cell senescence was remarkably prevented. Insulin-like growth factor-1 receptor was identified as a direct target of miR-297b-5p. Inhibition of the insulin-like growth factor-1 receptor prevented stearic acid-induced ß-cell senescence and dysfunction. Moreover, metformin alleviates the impairment of the miR-297b-5p inhibitor in ß-TC6 cells. Additionally, long-term consumption of a high-stearic-acid diet significantly increased senescence and reduced miR-297b-5p expression in mouse islets. CONCLUSIONS: These findings imply that metformin alleviates ß-cell senescence by stearic acid through upregulating miR-297b-5p to suppress insulin-like growth factor-1 receptor expression, thereby providing a potential target to not only prevent high fat-diet-induced ß-cell dysfunction but also for metformin therapy in type 2 diabetes.

Bioinspired CuZn-N/C Single-Atom Nanozyme with High Substrate Specificity for Selective Online Monitoring of Epinephrine in Living Brain.

Though many elegant laccase mimics have emerged, these mimics generally have no substrate selectivity as well as low activity, making it difficult to fulfill the demand for monitoring in physiological conditions. Herein, inspired by the Cu-N ligand structure in the active site of natural laccase, we revealed that a carbon nanomaterial with atomically dispersed Cu and Zn atoms (CuZn-N/C) and a well-defined ligand structure could function as an effective laccase mimic for selectively catalyzing epinephrine (EP) oxidation. Catalytic activity of the CuZn-N/C nanozyme was superior to those of Cu-N/C and Zn-N/C and featured a Km value nearly 3-fold lower than that of natural laccase, which indicated that CuZn-N/C has a better affinity for EP. Density functional theory (DFT) revealed the mechanism of the superior catalytic ability of dual-metal CuZn-N/C as follows: (1) the exact distance of the two metal atoms in the CuZn-N/C catalyst makes it suitable for adsorption of the EP molecule, and the CuZn-N/C catalyst can offer the second hydrogen bond that stabilizes the adsorption; (2) molecular orbitals and density of states indicate that the strong interaction between the EP molecule and CuZn-N/C is important for EP catalytic oxidization. Furthermore, a sensitive and selective online optical detection platform (OODP) is constructed for determining EP with a low limit of detection (LOD) of 0.235 µM and a linear range of 0.2-20 µM. The system allows real-time measurement of EP release in the rat brain in vivo following ischemia with dexmedetomidine administration. This work not only provides an idea of designing efficient laccase mimics but also builds a promising chemical platform for better understanding EP-related drug action for ischemic cerebrovascular illnesses and opens up possibilities to explore brain function.