[Spatial-temporal Variation in Water Quality of Rain-source Rivers in Shenzhen from 2015 to 2021 and Its Response to Rainfall].

Rain-source urban rivers have the characteristics of small water capacity， lack of dynamic water supply， and being easily polluted. This study analyzed the spatial and temporal distribution characteristics of river water quality and the response of characteristic pollutants to rainfall based on daily rainfall data and 21 water quality indicators of nine major river basins in Shenzhen （excluding Shenzhen-Shantou） from 2015 to 2021 by using the single-factor assessment method， comprehensive pollution index method， hierarchical cluster analysis， and Pearson correlation. The results showed that： ① in 2015， the water quality of most sections in the whole region was inferior Class V water. After October 2018， the overall water quality of rivers was greatly improved， which was consistent with the background of Shenzhen's special water control activities in 2018. By 2021， the water quality of approximately 62% of sections reached Class Ⅰ-Ⅲ water standards. ② The water pollution in the densely populated western part of Shenzhen was more serious than that in the eastern part， and the water pollution in the lower reaches of the estuaries and tributaries was more serious than that in the upper reaches. ③ The water quality of the Pingshan River， Guanlan River， Longgang River， and Maozhou River was significantly affected by rainfall. ④ The main characteristic pollution indexes of the Shenzhen River were DO， permanganate index， COD， BOD5， NH4+-N， TP， petroleum， and anionic surfactant. For the Pingshan River and Longgang River， rainfall increased the concentrations of TP and NH4+-N. For the Maozhou River， rainfall increased the concentrations of TP and COD. For the Shenzhen River， rainfall increased the concentrations of COD， TP， and NH4+-N. The above results reveal the spatio-temporal variation in rain-source river water quality in Shenzhen and its response to non-point source pollution caused by rainfall events and provide a scientific reference for building a higher quality water environment in Shenzhen.

Pore engineering of micro/mesoporous nanomaterials for encapsulation, controlled release and variegated applications of essential oils.

Essential oils have become increasingly popular in fields of medical, food and agriculture, owing to their strongly antimicrobial, anti-inflammation and antioxidant effects, greatly meeting demand from consumers for healthy and safe natural products. However, the easy volatility and/or chemical instability of active ingredients of essential oils (EAIs) can result in the loss of activity before realizing their functions, which have greatly hindered the widely applications of EAIs. As an emerging trend, micro/mesoporous nanomaterials (MNs) have drawn great attention for encapsulation and controlled release of EAIs, owing to their tunable pore structural characteristics. In this review, we briefly discuss the recent advances of MNs that widely used in the controlled release of EAIs, including zeolites, metal-organic frameworks (MOFs), mesoporous silica nanomaterials (MSNs), and provide a comprehensive summary focusing on the pore engineering strategies of MNs that affect their controlled-release or triggered-release for EAIs, including tailorable pore structure properties (e.g., pore size, pore surface area, pore volume, pore geometry, and framework compositions) and surface properties (surface modification and surface functionalization). Finally, the variegated applications and potential challenges are also given for MNs based delivery strategies for EAIs in the fields of healthcare, food and agriculture. These will provide considerable instructions for the rational design of MNs for controlled release of EAIs.

Pluripotency state transition of embryonic stem cells requires the turnover of histone chaperone FACT on chromatin.

The differentiation of embryonic stem cells (ESCs) begins with the transition from the naive to the primed state. The formative state was recently established as a critical intermediate between the two states. Here, we demonstrate the role of the histone chaperone FACT in regulating the naive-to-formative transition. We found that the Q265K mutation in the FACT subunit SSRP1 increased the binding of FACT to histone H3-H4, impaired nucleosome disassembly in vitro, and reduced the turnover of FACT on chromatin in vivo. Strikingly, mouse ESCs harboring this mutation showed elevated naive-to-formative transition. Mechanistically, the SSRP1-Q265K mutation enriched FACT at the enhancers of formative-specific genes to increase targeted gene expression. Together, these findings suggest that the turnover of FACT on chromatin is crucial for regulating the enhancers of formative-specific genes, thereby mediating the naive-to-formative transition. This study highlights the significance of FACT in fine-tuning cell fate transition during early development.

Characteristics of whole-body dynamic 18F-FDG PET/CT Patlak multi-parametric imaging in lung cancer and the influence of different delineation methods on quantitative parameters.

Background: Dynamic course of flourine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) Patlak muti-parametric imaging spatial distribution in the targeted tissues may reveal highly useful clinical information about the tissue's metabolic properties. The characteristics of the Patlak multi-parametric imaging in lung cancer and the influence of different delineation methods on quantitative parameters may provide reference for the clinical application of this new technology. Methods: A total of 27 patients with pathologically diagnosed lung cancer underwent whole-body dynamic 18F-FDG PET/CT examination before treatment. Parametric images of metabolic rate of FDG (MRFDG) and Patlak intercept (or distribution volume; DV) were generated using Patlak reconstruction. The values of primary lung cancer lesions, target-to-background ratio (TBR), and contrast-to-noise ratio (CNR) were investigated using contour delineation and boundary delineation. Statistical analysis was performed to analyze the relationship between multi-parametric images and clinicopathological features, and to compare the effects of contour delineation and boundary delineation on quantitative parameters. Results: MRFDG images showed higher TBR and CNR than did standardized uptake value (SUV) images. There were significant differences in MRFDG-max, MRFDG-mean, and MRFDG-peak among groups with different tumor diameters and pathology types (P<0.05). Moreover, the metabolic parameters of MRFDG were higher in patients with tumor diameters ≥3 cm and squamous carcinoma. The differences of the maximum and peak values of MRFDG and DV were not statistically significant in the different outlining method subgroups (all P>0.05). However, the difference of the mean values of MRFDG and DV were statistically significant in the different outline method groupings (all P<0.05). Conclusions: Dynamic 18F-FDG PET/CT Patlak multi-parametric imaging can obtain quantitative values for lung cancer with high TBR and CNR. Moreover, the multi-parameters are various from different pathology types to tumor size. Different delineation methods have a greater influence on the mean value of quantitative parameters.

P300/CBP Regulates HIF-1-Dependent Sympathetic Activation and Hypertension by Intermittent Hypoxia.

Obstructive sleep apnea (OSA), a widespread breathing disorder, leads to intermittent hypoxia (IH). Patients with OSA and IH-treated rodents exhibit heightened sympathetic nerve activity and hypertension. Previous studies reported transcriptional activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox) by HIF-1 (hypoxia-inducible factor-1) contribute to autonomic dysfunction in IH-treated rodents. Lysine acetylation, regulated by KATs (lysine acetyltransferases) and KDACs (lysine deacetylases), activates gene transcription and plays an important role in several physiological and pathological processes. This study tested the hypothesis that acetylation of HIF-1α by p300/CBP (CREB-binding protein) (KAT) activates Nox transcription, leading to sympathetic activation and hypertension. Experiments were performed on pheochromocytoma-12 cells and rats treated with IH. IH increased KAT activity, p300/CBP protein, HIF-1α lysine acetylation, HIF-1 transcription, and HIF-1 binding to the Nox4 gene promoter in pheochromocytoma-12 cells, and these responses were blocked by CTK7A, a selective p300/CBP inhibitor. Plasma norepinephrine (index of sympathetic activation) and blood pressures were elevated in IH-treated rats. These responses were associated with elevated p300/CBP protein, HIF-1α stabilization, transcriptional activation of Nox2 and Nox4 genes, and reactive oxygen species, and all these responses were absent in CTK7A-treated IH rats. These findings suggest lysine acetylation of HIF-1α by p300/CBP is an important contributor to sympathetic excitation and hypertension by IH.

Genome mining of actinomycin shunt products from Kitasatospora sp. YINM00002.

Actinomycins are known for their anti-tumor, antibacterial and antiviral activities, and in particular for the ability of actinomycin D as a clinical drug to treat a variety of cancers. In our ongoing work to obtain novel natural products from endophytic actinomycetes derived from traditional Chinese herbs, we identified the potential to produce actinomycins in YINM00002, a Kitasatospora strain derived from Polygonatum kingianum. According to genome mining, we isolated actinomycins D and V (1 and 2) and small amounts of 4-methyl-3-hydroxyanthranilic acid (4-MHA) derivates (3 and 4) from strain fermentation broth. The presence of actinrhater A (3) and actinrhater B (4) reveals a mysterious shunt pathway in the early stages of actinomycin D biosynthesis. Our study provides a fresh perspective for further discovery and modification of novel actinomycins.

Powering mesoporous silica nanoparticles into bioactive nanoplatforms for antibacterial therapies: strategies and challenges.

Bacterial infection has been a major threat to worldwide human health, in particular with the ever-increasing level of antimicrobial resistance. Given the complex microenvironment of bacterial infections, conventional use of antibiotics typically renders a low efficacy in infection control, thus calling for novel strategies for effective antibacterial therapies. As an excellent candidate for antibiotics delivery, mesoporous silica nanoparticles (MSNs) demonstrate unique physicochemical advantages in antibacterial therapies. Beyond the delivery capability, extensive efforts have been devoted in engineering MSNs to be bioactive to further synergize the therapeutic effect in infection control. In this review, we critically reviewed the essential properties of MSNs that benefit their antibacterial application, followed by a themed summary of strategies in manipulating MSNs into bioactive nanoplatforms for enhanced antibacterial therapies. The chemically functionalized platform, photo-synergized platform, physical antibacterial platform and targeting-directed platform are introduced in details, where the clinical translation challenges of these MSNs-based antibacterial nanoplatforms are briefly discussed afterwards. This review provides critical information of the emerging trend in turning bioinert MSNs into bioactive antibacterial agents, paving the way to inspire and translate novel MSNs-based nanotherapies in combating bacterial infection diseases.

Competitive immunoassay using enzyme-regulated Fe3O4@COF/Fe3+ fluorescence probe for natural chloramphenicol detection.

Accurate and sensitive detection of chloramphenicol (CAP) in natural samples is essential for ensuring human health. Herein, an enzyme-regulated fluorescence sensor using Fe3O4@COF/Fe3+ probe, is developed for CAP determination. Fe3O4@COF, synthesized via hydrothermal method, exhibits dual functions as a magnetic carrier and signal probe. Bovine serum albumin conjugated-chloramphenicol, adsorbed on the surface of Fe3O4@COF, competes with CAP for antibody binding. The antibody interacts with alkaline phosphatase via the biotin-streptavidin system. Meanwhile, ascorbic acid, produced from the enzyme-catalyzed reaction dominated by alkaline phosphatase, effectively restores the fluorescence of Fe3O4@COF that is quenched by Fe3+. After experimental verification and gradual optimization, a logarithmic linear relationship between CAP concentration and fluorescence intensity is established in the range of 2 × 10-4∼10 µg mL-1, with a good limit of detection (9.2 × 10-5 µg mL-1). Proposed method exhibits excellent stability (15 days) and reusability (8 cycles), providing a sensitive and reliable method for accurate CAP detection. The readouts show good agreement with HPLC and recoveries during laboratory and natural CAP analysis.

Distinct gut bacterial composition in Anoplophora glabripennis reared on two host plants.

Anoplophora glabripennis (Coleoptera: Cerambycidae: Lamiinae) is an invasive wood borer pest that has caused considerable damage to forests. Gut bacteria are of great importance in the biology and ecology of herbivores, especially in growth and adaptation; however, change in the gut bacterial community of this pest feeding on different hosts is largely unknown. In this study, we investigated the gut bacterial communities of A. glabripennis larvae fed on different preferred hosts, Salix matsudana and Ulmus pumila, using 16S rDNA high-throughput sequencing technology. A total of 15 phyla, 25 classes, 65 orders, 114 families, 188 genera, and 170 species were annotated in the gut of A. glabripennis larvae fed on S. matsudana or U. pumila using a 97% similarity cutoff level. The dominant phyla were Firmicutes and Proteobacteria and the core dominant genera were Enterococcus, Gibbsiella, Citrobacter, Enterobacter, and Klebsiella. There was significantly higher alpha diversity in the U. pumila group than in the S. matsudana group, and principal co-ordinate analysis showed significant differences in gut bacterial communities between the two groups. The genera with significant abundance differences between the two groups were Gibbsiella, Enterobacter, Leuconostoc, Rhodobacter, TM7a, norank, Rhodobacter, and Aurantisolimonas, indicating that the abundance of larval gut bacteria was affected by feeding on different hosts. Further network diagrams showed that the complexity of the network structure and the modularity were higher in the U. pumila group than in the S. matsudana group, suggesting more diverse gut bacteria in the U. pumila group. The dominant role of most gut microbiota was related to fermentation and chemoheterotrophy, and specific OTUs positively correlated with different functions were reported. Our study provides an essential resource for the gut bacteria functional study of A. glabripennis associated with host diet.

An advanced ratiometric molecularly imprinted sensor based on metal ion reoxidation for indirect and ultrasensitive glyphosate detection in fruit.

An indirect and ultrasensitive ratiometric molecularly imprinted (MIP) sensor, based on metal ion reoxidation, is introduced for glyphosate (GLY) determination in fruit. As high-performance signal amplification substrates, carbon nanotubes (MWCNTs) and gold nanoparticles (AuNPs) are conveniently modified on GCE. The artificial antibody-MIP membrane, presents typical three-dimensional structure to GLY template. Built-in reference methylene blue (MB) is directly electropolymerized on MWCNTs-Au/GCE. Particularly, Cu2+ and GLY interestingly form chelate complex, and the Cu2+ (ICu) in Cu(Ⅱ)-GLY-complex can be reoxidized, and indirectly quantizes GLY. The reference signal (IMB) presents noteworthy stability with different GLY levels, and the ratiometric readout (ICu/IMB) is recognized as a more trustworthy indicator to quantize GLY. Proposed sensor presents broad range as 1.73 âˆ¼ 400 ng/mL, and limit of detection is well found as 0.24 ng/mL (S/N = 3). Finally, as-fabricated method is verified with standard HPLC in real-fruit-sample, and the errors and recovery rates are calculated as 3.4% âˆ¼ 6.7% and 94.4% âˆ¼ 104.6%, respectively.

Flexible-fabricated sensor module with programmable magnetic actuators coupled to L-cysteine functionalized Ag@Fe3O4 complexes for Cu2+ detection in fish tissues.

Heavy metal contamination for seafood, particularly fish, is arising great concerns, and consequentially it is necessary to develop a simple and direct detection method. In this work, Ag@Fe3O4 is successfully prepared by simple solvothermal method, and we present a flexible-fabricated sensor module with assembled programmable magnetic actuators. The resulting sensor integrates a three-electrode system with two programmable magnetic actuators at the bottom of the device, which regulates the amount of current by adjusting the brake to control the adsorption force and vibration. The L-Cysteine functionalized Ag@Fe3O4 is coated on the surface of the electrode, then the Cu2+ is dropped into the reaction tank. Its performance is studied by cyclic voltammetry and electrochemical impedance spectroscopy, and the key experimental conditions such as deposition potential, deposition time, and electrolyte pH are gradually optimized. Under optimal conditions, Cu2+ can be detected over a wide linear range (0.01 ~ 4 µM) and at a low LOD (0.34 nM). The results show that the proposed method has a good application prospect in the detection of Cu2+. This method is successfully applied to Cu2+ analysis in fish samples with an acceptable recovery of 93 ~ 102%.

A ratiometric electrochemical sensor for detecting lead in fish based on the synergy of semi-complementary aptamer pairs and Ag nanowires@zeolitic imidazolate framework-8.

This work describes the synergistic application of semi-complementary aptamer pairs and signals on-off ratio strategies on glassy carbon electrodes (GCE) for detecting lead ions (Pb2+) in fish. Gold nanoparticles (AuPNs) as the electrode substrate can provide added binding sites for the aptamers and improve the conductivity of the electrodes. Pb2+ aptamers containing ferrocene (Fc) molecules act as molecular recognizers in the sensing system. In the presence of target ions, Fc signals are affected by conformational changes of the aptamer. The "Ag nanowires@zeolitic imidazolate framework-8 with methylene blue (AgNWs@ZIF-8/MB)" can be semi-complementary to the Pb2+ aptamer after binding to single-stranded DNA (S1). However, S1/AgNWs@ZIF-8/MB self-assembled with Pb2+ aptamer (Apt) by hybridization incubation was quickly replaced by Pb2+ competitively, resulting in the loss of methylene blue (MB) signaling molecules. Hence, the internal reference signal (MB) and conformation change signal (Fc) comprise the ratio sensing system well. Morphology, spectroscopy, and electrochemistry methods have validated the modification and sensing behaviors. The used Apt has made considerable progress in analytical performance. In interference studies and stability checks, the ratio measurement signal IFc/IMB is a more reliable signal than the single signal readout. Following a log-linear relationship, this sensor provides a wide linear range. Furthermore, the proposed sensor can be used to determine Pb2+ in fish samples, and the results agree with those obtained using ICP-MS and recovery tests.

Rambutan-liked Pickering emulsion stabilized by cellulose nanocrystals for enhancing anti-bacterial activity and anti-inflammatory effect of Chimonanthus nitens Oliv. essential oil.

Owing to volatility and poor water solubility, the medical application of Chimonanthus nitens Oliv. essential oil (CEO) in the fields of medicine was strictly limited. To tackle this problem, a novel CEO loaded rambutan-liked Pickering emulsion (CEO-RPE) with a spiky surface was effectively designed by coating with carboxymethyl cellulose sodium modified cellulose nanocrystals (CCN) as stabilizer. The effect of CCN concentration on the formation and stabilization of CEO-RPE was investigated. The results showed that CEO-RPE stabilized by 1 % CCN had a smaller droplet size and exhibited a rambutan-liked surface, and was stabilized against concentrated salt and high pH condition due to the steric barrier of CCN that covered in the droplet surface. Subsequently, the antibacterial performance of CEO-RPE was investigated against E. coli, S. aureus, P. aeruginosa, and S. pneumoniae by determining the minimum inhibitory concentration (MIC). The results showed that the CEO-RPE exhibited higher antibacterial activity compared to CEO, which could be attributed to its effective adhesion to the cell membrane of bacteria. In addition, the results of anti-inflammatory experiments showed that CEO-RPE also exhibited strong anti-inflammatory effect on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats. Therefore, the CCN stabilized rambutan-liked Pickering emulsion seemed to be a promising strategy to increase the antibacterial and anti-inflammatory activity of CEO.

Sponge-liked Silica Nanoporous Particles for Sustaining Release and Long-Term Antibacterial Activity of Natural Essential Oil.

To improve the sustained release and long-term antibacterial activity of Chimonanthus nitens Oliv. essential oil (CEO), novel sponge-liked nanoporous silica particles (SNP) were synthesized via the soft template method, which was employed as a biocompatible carrier to prepare spong-liked nanoporous silica particles loading with CEO (CEO-SNP) through physical adsorption. The structure and properties of the samples were characterized via N2 adsorption/desorption measurements, thermogravimetry (TGA), Fourier transform infrared, SEM and TEM. The result showed that the SNP exhibited an excellent loading capability of CEO up to 76.3%. The thermal stability and release behavior of the CEO were significantly improved via the physical adsorption of the SNP materials. The release profile of CEO was in accordance with the first-order kinetic model, which meant that the release mechanism was drug Fick's diffusion. The antibacterial evaluation results demonstrated that the CEO-SNP exhibited strong antibacterial activity against S. aureus, E. coli and P. aeruginosa. The antibacterial results have shown that the CEO-SNP could destroy the cell structure of bacteria, and result in the generation of oxidative stress and the release of nucleic acid. After storage of 30 d at 25 °C, the CEO-SNP still had the stronger antibacterial activity towards S. aureus, E. coli and P. aeruginosa in comparison with CEO. Therefore, the sponge-like silica nanoporous particles seemed to be a promising carrier for long-term stability and antibacterial delivery of CEO.

Childhood environment and adulthood food addiction: Testing the multiple mediations of life history strategies and attitudes toward self.

Food addiction is associated with both physical and mental health conditions, such as obesity and depression, and is considered a public health problem. Based on life history (LH) theory, this study aimed to test the association between unpredictable childhood environment and food addiction in adulthood and to examine LH strategies and attitudes toward self as psychological mediators of this association. A random sample of 1010 adults, aged from 18 to 88 years (44.8% male; Mage = 38.52, SDage = 14.53), voluntarily participated in an anonymous telephone survey conducted in Macao, China. The results of a path analysis showed the significant and positive direct effect of childhood unpredictability on food addiction and its negative association with slow LH strategy, which in turn was negatively correlated with food addiction. In addition, slow LH strategy and self-judgment, rather than self-kindness, acted as serial mediators in the association between childhood unpredictability and food addiction. These findings support the applicability of LH theory to understanding food addiction, as well as pointing to the potential risk effect of self-judgment for food addiction in adulthood. Self-judgment reduction may be a potential supplementary approach for future food addiction intervention.

Ratiometric Detection of Ochratoxin A Using a Regenerable COF-Au-MB-Apt Signal Probe on a Thermal-Regulated Sensor Module.

Ochratoxin A (OTA) frequently contaminates grains and consequently threatens human health. Herein, we develop a regenerable signal probe and apply it to a Au-based screen-printed electrode module (SPE) for OTA determination. The signal probe, containing a structural covalent organic framework, gold nanoparticles (AuNPs), indicative methylene blue (MB), and a highly selective aptamer, is synthesized with hydrothermal and self-assembly methods. The SPE is permanently functionalized with Prussian blue (PB), AuNPs, and semicomplementary ssDNA. The signal probe, absorbed onto this SPE via hybridization, is competitively expelled by OTA, providing a ratiometric readout of ΔIMB/IPB. Probe regeneration, to erase expired COF-Au-MB-Apt after each analysis, is established with the synergy of OTA-conducted Apt-ssDNA dissociation and on-chip thermal regulation. This advantage powerfully guarantees reduplicative analyses by avoiding irreversible Apt-OTA combination and accumulation on the sensing interface. Regenerations are performed in repetitive cycles (N = 7) with 98.5% reproduction efficiency, and IMB and IPB fluctuations are calculated as 1.45 and 1.12%. This method shows log-linear OTA response in a wide range from 0.2 pg/mL to 0.6 µg/mL, and the limit of detection is 0.12 pg/mL. During natural OTA determinations, recommended readouts match well with HPLC with less than 4.82% relative error.

Dynamic changes of gut bacterial communities present in larvae of Anoplophora glabripennies collected at different developmental stages.

The Asian long-horned beetle, Anoplophora glabripennies (Motschulsky), is a destructive wood-boring pest that is capable of killing healthy trees. Gut bacteria in the larvae of the wood-boring pest is essential for the fitness of hosts. However, little is known about the structure of the intestinal microbiome of A. glabripennies during larval development. Here, we used Illumina MiSeq high-throughput sequencing technology to analyze the larval intestinal bacterial communities of A. glabripennies at the stages of newly hatched larvae, 1st instar larvae and 4th instar larvae. Significant differences were found in larval gut microbial community structure at different larvae developmental stages. Different dominant genus was detected during larval development. Acinetobacter were dominant in the newly hatched larvae, Enterobacter and Raoultella in the 1st instar larvae, and Enterococcus and Gibbsiella in the 4th instar larvae. The microbial richness in the newly hatched larvae was higher than those in the 1st and 4th instar larvae. Many important functions of the intestinal microbiome were predicted, for example, fermentation and chemoheterotrophy functions that may play an important role in insect growth and development was detected in the bacteria at all tested stages. However, some specific functions are found to be associated with different development stages. Our study provides a theoretical basis for investigating the function of the intestinal symbiosis bacteria of A. glabripennies.

The Extract of Angelica sinensis Inhibits Hypoxia-Reoxygenation and Copper-Induced Oxidative Lesions and Apoptosis in Branchiae and Red Blood Corpuscles of Fish.

The study explored the effects of Angelica sinensis extract (AsE) on oxidative lesions and apoptosis in branchiae and red blood corpuscles in hypoxia-reoxygenation (HR) and Cu-treated carp (Cyprinus carpio var. Jian). After feeding trial for 30 days, the carp were exposed to HR and CuSO4. The results indicated that dietary AsE increased the durative time, decreased the oxygen consumption rate, suppressed ROS generation and cellular component oxidation, decreased enzymatic antioxidant activity and reduced glutathione (GSH) levels in red blood corpuscles and branchiae in carp under hypoxia. Moreover, dietary AsE avoided the loss of Na+,K+-ATPase, metabolic and antioxidant enzyme activities, ROS generation and cellular component oxidation, as well as the increase in caspase-8, 9, and 3 activities in the branchiae of the carp and inhibited ROS generation. It furthermore avoided the loss of Na+,K+-ATPase and metabolic enzyme activities, the decrease in GSH levels and hemoglobin content, the increase in the activities of caspase-8, 9, and 3 and the increase in the levels of cytochrome c and phosphatidylserine exposure in the red blood corpuscles of Cu-exposed carp. The present results suggested that dietary AsE improved hypoxia tolerance and inhibited HR or Cu-triggered oxidative lesions and apoptosis. Therefore, AsE can be utilized as a natural inhibitor of Cu and HR stress in fish.

Therapeutic effects and mechanisms of N-(9,10-anthraquinone-2-ylcarbonyl) xanthine oxidase inhibitors on hyperuricemia.

Objective: To observe the antioxidative effects of N-(9,10-anthraquinone-2-ylcarbonyl) xanthine oxidase inhibitors (NAY) in vitro and in vivo models of hyperuricemia and explore the mechanism. Methods: A classical experimental method of acute toxicity and a chronic toxicity test were used to compare the toxic effects of different doses of NAY in mice. The hyperuricemia mouse model was established by gavage of potassium oxonate in vivo. After treatment with different doses of NAY (low dose: 10 mg/kg, medium dose: 20 mg/kg, and high dose: 40 mg/kg) and allopurinol (positive drug, 10 mg/kg), observe the levels of uric acid (UA), creatinine (CRE), and urea nitrogen (BUN) in urine and serum, respectively, and detect the activities of xanthine oxidase in the liver. The hyperuricemia cell model was induced by adenosine and xanthine oxidase in vitro. The cells were given different doses of NAY (50, 100, and 200 µmol/L) and allopurinol (100 µmol/L). Then the culture supernatant UA level of the medium was measured. The next step was to detect the xanthine oxidase activity in the liver and AML12 cells, and the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammatory factors in the kidney and serum of mice. Western blot was used to detect xanthine oxidase protein expression in mouse liver tissue and AML12 cells, ASC, Caspase-1, NLRP3, GLUT9, OAT1, and OAT3 protein expression in mouse kidney tissue and HK-2 cells. Hematoxylin-eosin staining was used to stain the liver and kidney tissues of mice and observe the tissue lesions. Results: NAY had little effect on blood routine and biochemical indexes of mice, but significantly reduced the serum UA level. NAY significantly reduced the level of UA in hyperuricemia mice and cells by inhibiting xanthine oxidase activity and reduced the levels of TNF-α, IL-6, and other inflammatory factors in serum and kidney of mice. NAY can inhibit inflammation by inhibiting the NLRP3 pathway. In addition, NAY can downregulate GLUT9 protein expression and upregulate OAT1 and OAT3 protein expression to reduce the UA level by promoting UA excretion and inhibiting UA reabsorption. Conclusion: These findings suggested that NAY produced dual hypouricemic actions. On the one hand, it can inhibit the formation of UA by inhibiting xanthine oxidase inhibitors activity, and on the other hand, it can promote the excretion of UA by regulating the UA transporter. It provides new ideas for the development of hyperuricemia drugs in the future.

Biomaterial-targeted precision nanoparticle delivery to the injured spinal cord.

Drug delivery requires precision in timing, location, and dosage to achieve therapeutic benefits. Challenges in addressing all three of these critical criteria result in poor temporal dexterity, widespread accumulation and off-target effects, and high doses with the potential for toxicity. To address these challenges, we have developed the BiomatErial Accumulating Carriers for On-demand Nanotherapy (BEACON) platform that utilizes an implantable biomaterial to serve as a target for systemically delivered nanoparticles (NPs). With the BEACON system, administered NPs are conjugated with a ligand that has high affinity for a receptor in the implanted biomaterial. To test BEACON, an in vivo spinal cord injury (SCI) model was used as it provides an injury model where the three identified criteria can be tested as it is a dynamic and complicated injury model with no currently approved therapies. Through our work, we have demonstrated temporal dexterity in NP administration by injecting 6 days post-SCI, decreased off-target accumulation with a significant drop in liver accumulation, and retention of our NPs in the target biomaterial. The BEACON system can be applied broadly, beyond the nervous system, to improve systemically delivered NP accumulation at an implanted biomaterial target. STATEMENT OF SIGNIFICANCE: Targeted drug delivery approaches have the potential to improve therapeutic regimens for patients on a case-by-case basis. Improved localization of a therapeutic to site of interest can result in increased efficacy and limit the need for repeat dosing. Unfortunately, targeted strategies can fall short when receptors on cells or tissues are too widespread or change over the course of disease or injury progression. The BEACON system developed herein eliminates the need to target a cell or tissue receptor by targeting an implantable biomaterial with location-controllable accumulation and sustained presentation over time. The targeting paradigm presented by BEACON is widely applicable throughout tissue engineering and regenerative medicine without the need to retool for each new application.