Self-Reinforced MOF-Based Nanogel Alleviates Osteoarthritis by Long-Acting Drug Release.

Intra-articular injection of drugs is an effective strategy for osteoarthritis (OA) treatment. However, the complex microenvironment and limited joint space result in rapid clearance of drugs. Herein, a nanogel-based strategy is proposed for prolonged drug delivery and microenvironment remodeling. Nanogel is constructed through the functionalization of hyaluronic acid (HA) by amide reaction on the surface of Kartogenin (KGN)-loaded zeolitic imidazolate framework-8 (denoted as KZIF@HA). Leveraging the inherent hydrophilicity of HA, KZIF@HA spontaneously forms nanogels, ensuring extended drug release in the OA microenvironment. KZIF@HA exhibits sustained drug release over one month, with low leakage risk from the joint cavity compared to KZIF, enhanced cartilage penetration, and reparative effects on chondrocytes. Notably, KGN released from KZIF@HA serves to promote extracellular matrix (ECM) secretion for hyaline cartilage regeneration. Zn2+ release reverses OA progression by promoting M2 macrophage polarization to establish an anti-inflammatory microenvironment. Ultimately, KZIF@HA facilitates cartilage regeneration and OA alleviation within three months. Transcriptome sequencing validates that KZIF@HA stimulates the polarization of M2 macrophages and secretes IL-10 to inhibit the JNK and ERK pathways, promoting chondrocytes recovery and enhancing ECM remodeling. This pioneering nanogel system offers new therapeutic opportunities for sustained drug release, presenting a significant stride in OA treatment strategies.

Coronary microvascular dysfunction.

Coronary microvascular dysfunction (CMD) is a key mechanism underlying ischemic heart disease (IHD), yet its diagnosis and treatment remain challenging. This article presents a comprehensive overview of CMD research, covering its pathogenesis, diagnostic criteria, assessment techniques, risk factors, and therapeutic strategies. Additionally, it highlights the prospects for future CMD research. The article aims at advocating early and effective intervention for CMD and improving the prognosis of IHD.

An insertion of transposon in DcNAP inverted its function in the ethylene pathway to delay petal senescence in carnation (Dianthus caryophyllus L.).

Petal senescence is the final stage of flower development. Transcriptional regulation plays key roles in this process. However, whether and how post-transcriptional regulation involved is still largely unknown. Here, we identified an ethylene-induced NAC family transcription factor DcNAP in carnation (Dianthus caryophyllus L.). One allele, DcNAP-dTdic1, has an insertion of a dTdic1 transposon in its second exon. The dTdic1 transposon disrupts the structure of DcNAP and causes alternative splicing, which transcribes multiple domain-deleted variants (DcNAP2 and others). Conversely, the wild type allele DcNAP transcribes DcNAP1 encoding an intact NAC domain. Silencing DcNAP1 delays and overexpressing DcNAP1 accelerates petal senescence in carnation, while silencing and overexpressing DcNAP2 have the opposite effects, respectively. Further, DcNAP2 could interact with DcNAP1 and interfere the binding and activation activity of DcNAP1 to the promoters of its downstream target ethylene biosynthesis genes DcACS1 and DcACO1. Lastly, ethylene signalling core transcriptional factor DcEIL3-1 can activate the expression of DcNAP1 and DcNAP2 in the same way by binding their promoters. In summary, we discovered a novel mechanism by which DcNAP regulates carnation petal senescence at the post-transcriptional level. It may also provide a useful strategy to manipulate the NAC domains of NAC transcription factors for crop genetic improvement.

Studies on Atrial Fibrillation and Venous Thromboembolism in the Past 20 Years: A Bibliometric Analysis Via CiteSpace and VOSviewer.

The conjunction of atrial fibrillation (AF) and venous thromboembolism (VTE) is common in clinical practice. Over the last 2 decades, a significant number of articles (2500) have been published about AF and VTE. To effectively analyze and present these vast amounts of information, this study uses bibliometric research methods to categorize and consolidate these publications. The number of publications has increased yearly, especially since 2012. The United States was the most prolific country, with 1054 studies published. The most productive institution was McMaster University. Gregory Y.H. Lip was the most prolific author. The keyword analysis identified that the research focuses from 2003 to 2014 were factor Xa inhibitor, dabigatran etexilate, direct thrombin inhibitor, double-blind, deep vein thrombosis, molecular weight heparin, stroke prevention, etc. From 2015 to 2016, research mainly focused on venous thromboembolism, antithrombotic therapy, anticoagulant, warfarin, atrial fibrillation, stroke, and pulmonary embolism. Studies during 2017 to 2022 focused on apixaban, direct oral anticoagulant, rivaroxaban, dabigatran, hemorrhage, edoxaban, medicine efficacy and safety, risk factors, clinical management, and vitamin K antagonists. Since 2018, novel oral anticoagulants have been the most commonly used keywords. On the whole, most studies of AF and VTE focus on pathogenesis and therapeutic drugs. The causal relationship between AF and VTE, the effectiveness and safety of novel oral anticoagulants in the treatments, the anticoagulant regimen of AF and VTE co-disease, and the treatment regimen for vulnerable populations such as the elderly or obese people were the focus of current research and will continue to be the central point of future research.

The mutual regulation between DcEBF1/2 and DcEIL3-1 is involved in ethylene induced petal senescence in carnation (Dianthus caryophyllus L.).

Carnation (Dianthus caryophyllus L.) is a respiratory climacteric flower, comprising one of the most important cut flowers that is extremely sensitive to plant hormone ethylene. Ethylene signaling core transcription factor DcEIL3-1 plays a key role in ethylene induced petal senescence in carnation. However, how the dose of DcEIL3-1 is regulated in the carnation petal senescence process is still not clear. Here, we screened out two EBF (EIN3 Binding F-box) genes, DcEBF1 and DcEBF2, which showed quick elevation by ethylene treatment according to the ethylene induced carnation petal senescence transcriptome. Silencing of DcEBF1 and DcEBF2 accelerated, whereas overexpression of DcEBF1 and DcEBF2 delayed, ethylene induced petal senescence in carnation by influencing DcEIL3-1 downstream target genes but not DcEIL3-1 itself. Furthermore, DcEBF1 and DcEBF2 interact with DcEIL3-1 to degrade DcEIL3-1 via an ubiquitination pathway in vitro and in vivo. Finally, DcEIL3-1 binds to the promoter regions of DcEBF1 and DcEBF2 to activate their expression. In conclusion, the present study reveals the mutual regulation between DcEBF1/2 and DcEIL3-1 during ethylene induced petal senescence in carnation, which not only expands our understanding about ethylene signal regulation network in the carnation petal senescence process, but also provides potential targets with respect to breeding a cultivar of long-lived cut carnation.

DcWRKY33 promotes petal senescence in carnation (Dianthus caryophyllus L.) by activating genes involved in the biosynthesis of ethylene and abscisic acid and accumulation of reactive oxygen species.

Carnation (Dianthus caryophyllus L.) is one of the most famous and ethylene-sensitive cut flowers worldwide, but how ethylene interacts with other plant hormones and factors to regulate petal senescence in carnation is largely unknown. Here we found that a gene encoding WRKY family transcription factor, DcWRKY33, was significantly upregulated upon ethylene treatment. Silencing and overexpression of DcWRKY33 could delay and accelerate the senescence of carnation petals, respectively. Abscisic acid (ABA) and H2 O2 treatments could also accelerate the senescence of carnation petals by inducing the expression of DcWRKY33. Further, DcWRKY33 can bind directly to the promoters of ethylene biosynthesis genes (DcACS1 and DcACO1), ABA biosynthesis genes (DcNCED2 and DcNCED5), and the reactive oxygen species (ROS) generation gene DcRBOHB to activate their expression. Lastly, relationships are existed between ethylene, ABA and ROS. This study elucidated that DcWRKY33 promotes petal senescence by activating genes involved in the biosynthesis of ethylene and ABA and accumulation of ROS in carnation, supporting the development of new strategies to prolong the vase life of cut carnation.

miR-532-5p Inhibits Non-Small Cell Lung Cancer Progression In Vivo and In Vitro by Targeting Yin Yang 1.

Lung cancer is a common cancer that is familiar to people and has the highest global incidence; among all lung cancer patients, 85% are non-small cell lung cancer (NSCLC). A number of microRNAs (miRNAs), including miR-532-5p, are implicated in the pathophysiological processes of tumorigenesis. However, the mechanism of miR-532-5p in NSCLC remains unclear. In the current study, the expression of miR-532-5p was found to be markedly downregulated in clinical NSCLC tissues and cell lines. Further study indicated that ectopic expression of miR-532-5p inhibited NSCLC cell proliferation and invasion while accelerating in vitro, but silencing miR-532-5p had an opposite result. Furthermore, functional experiments revealed that miR-532-5p effectively blocked tumor growth in a xenograft tumor mouse model. Bioinformatics and luciferase reporter analysis verified that Yin Yang 1 (YY1) transcripts are targets of miR-532-5p. Moreover, the expression of YY1 was negatively regulated by miR-532-5p in NSCLC cells. In vivo assays indicated that downregulation of YY1 inhibited tumor growth. Notably, overexpression of YY1 effectively counteracted the tumor-suppressing effects of miR-532-5p in vitro and in vivo. In summary, this study demonstrated the tumor-suppressive role of miR-532-5p in NSCLC by regulating YY1 in vitro and in vivo.

An ultrasensitive electrochemical sensor based on in situ synthesized manganese dioxide/gold nanoparticles nanocomposites for rapid detection of methylmercury in foodstuffs.

The inclusion of methylmercury (CH3Hg+) in the environment and food chain has aroused wide concern due to its high neurotoxicity and cumulative effects. Herein, a highly sensitive electrochemical sensor based on manganese dioxide (MnO2)/gold nanoparticles (AuNPs) composites is fabricated for CH3Hg+ detection in food. The MnO2/AuNPs nanocomposites were synthesized in situ on the surface of a glassy carbon electrode by an electrodeposition method and were characterized by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). The resulting MnO2/AuNPs modified electrode exhibited a large active surface area, enhanced conductivity and excellent electrocatalytic activity toward CH3Hg+ due to the synergistic effect of MnO2 and AuNPs. Square wave anodic stripping voltammetry (SWASV) was used as the sensing technique for CH3Hg+, and the stripping peak current showed a good linear relationship with CH3Hg+ concentration in the range of 0.7-15 µg L-1 with a detection limit of 0.051 µg L-1. Besides, the interference from Hg2+ associated with CH3Hg+ detection can be avoided by the addition of diethylene triamine pentaacetic acid (DTPA). The as-prepared sensor was applied to detect CH3Hg+ in various food samples with satisfactory recoveries, thus providing a promising platform for rapid screening of methylmercury residues.

Reductive Radical Annulation Strategy toward Bicyclo[3.2.1]octanes: Synthesis of ent-Kaurane and Beyerane Diterpenoids.

Here we report a general [3 + 2] radical annulation that allows the facile construction of bicyclo[3.2.1]octane motifs in ent-kaurane- and beyerane-type diterpenoids. This radical annulation is difficult to control but was realized by harnessing an unprecedented and counterintuitive effect of TEMPO. Eleven natural products with a wide array of oxidation states are easily prepared, demonstrating the powerful utility of this straightforward synthetic strategy.

Association of Serum FAM19A5 with Cognitive Impairment in Vascular Dementia.

OBJECTIVE: Family with sequence similarity 19 member A5 (FAM19A5), a novel chemokine-like peptide, is a secreted protein mainly expressed in the brain. FAM19A5 was recently found to be involved in a variety of neurological diseases; however, its correlation with vascular dementia (VaD) remains unclear. The aim of the study is to explore the association between serum FAM19A5 and cognitive impairment in subjects with VaD. METHOD: 136 VaD subjects and 81 normal controls were recruited in the study. Their demographic and clinical baseline data were collected on admission. All subjects received Mini-Mental State Examination (MMSE) evaluation, which was used to test their cognitive functions. A sandwich enzyme-linked immunosorbent assay (ELISA) was applied to detect the serum levels of FAM19A5. RESULTS: No significant differences were found between the two groups regarding the demographic and clinical baseline data (p > 0.05). The serum FAM19A5 levels were significantly higher compared to normal controls (p < 0.001). The Spearman correlation analysis indicated that serum FAM19A5 levels and MMSE scores have a significant negative correlation in VaD patients (r = -0.414, <0.001). Further multiple regression analysis indicated that serum FAM19A5 levels were independent risk predictors for cognitive functions in VaD (ß = 0.419, p = 0.031). CONCLUSION: The serum FAM19A5 level of VaD patients is significantly increased, which may serve as a biomarker to predict cognitive function of VaD.

Effects of sang-qi granules on blood pressure and endothelial dysfunction in stage I or II hypertension: study protocol for a randomized double-blind double-simulation controlled trial.

BACKGROUND: Worldwide, hypertension is an important public health challenge because of its high prevalence and the concomitant risks of cardiovascular disease. It induces half of the coronary heart disease and approximately two-thirds of the cerebrovascular disease burden. Vascular endothelial dysfunction has important roles in the pathophysiology of essential hypertension. Types I and II hypertension can be treated with sang-qi granules (SQG), a Chinese herbal formula. Several experimental studies on animals have shown that SQG can lower blood pressure and myocardial fibrosis by suppressing inflammatory responses. However, no standard clinical trial has confirmed this. Whether SQG can improve endothelial cell function is unknown. METHODS/DESIGN: In this randomized double-blind double-simulation controlled trial, 300 patients with stage I or II hypertension will be recruited and randomly allocated in a 1:1:1 ratio to group A (treatment with SQG and placebo instead of Losartan), group B (treatment with Losartan and placebo instead of SQG), and group C (treatment with SQG and Losartan). In this study, 10 g of SQG (or its placebo) will be administrated twice a day and 50 mg of Losartan (or its placebo) will be administrated once in the morning. The primary endpoint is the drug efficiency for each of the three groups. The secondary endpoints are the change in average systolic and diastolic blood pressure during the day and the night, the change in the rate at which blood pressure drops at night, assessment of target organ damage (heart rate variability, ankle-brachial pressure index, and pulse wave velocity), assessment of any improvement in symptoms (Hypertension Symptom Scale, syndrome integral scale in traditional Chinese medicine, Pittsburgh Sleep Quality Index Scale, Self-Rating Anxiety Scale, Self-Rating Depression Scale, and the 36-Item Short Form Health Survey), blood lipids, serum indicators of vascular function (changes in serum levels of ET-1, TXA2, NO, and PGI2), and safety indicators. DISCUSSION: This study aims to provide clinical evidence on the efficacy and safety of SQG in the treatment of hypertension. Moreover, the possible mechanism by which SQG may lower blood pressure will be explored by observing the protective effect of SQG on vascular endothelial function, as well as its effect on related clinical symptoms, risk factors, and the target organs of hypertension. TRIAL REGISTRATION: Chinese Clinical Trials Registry, ChiCTR1800016427. Registered on 1 June 2018.

Design of a subwavelength all-metal grating for generating azimuthally polarized beams based on modified particle swarm optimization.

A subwavelength metal grating for generating azimuthally polarized beams was designed. The grating material was determined by calculating the total thermal conductivity coefficient. A modified particle swarm optimization (PSO), which has a two-step algorithm structure, and a particle position-determined inertia weight was performed to establish the grating's structural parameters. Results show that an Au-Ti-Cu all-metal structure provides good thermal conductivity. A high duty cycle structure gives the grating high polarization selectivity of approximately 82.63% at 10.6 µm and a minimum of 26.39% in the 9.6-11.6 µm band. The modified PSO is more efficient and requires fewer calculations while maintaining accuracy. The geometrical parameter tolerances were also analyzed. The groove depth fabrication tolerance is 200 nm, and the sidewall angle fabrication tolerance is 19°, which means that the optimized structure is insensitive to structural parameter deviations.

The effect of ultrasonic vibration and surfactant additive on fabrication of 53.5gr/mm silicon echelle grating with low surface roughness in alkaline KOH solution.

In the silicon echelle grating fabrication process, the "pseudo-mask" formed by the hydrogen bubbles generated during the etching process is the reason causing high surface roughness and poor surface quality of blazed plane. Based upon the ultrasonic mechanical effect and contact angle reduced by surfactant additive, ultrasonic vibration, isopropyl alcohol (IPA) and 2,4,7,9-Tetramethyl-5-decyne-4,7-diol (TMDD) were used to improve surface quality of 53.5gr/mm echelle grating. The surface roughness Rq is smaller than 18nm, 7nm and 2nm when using ultrasonic vibration, IPA and TMDD respectively. The surface roughness Rq is smaller than 5nm and 1.5nm respectively when combining ultrasonic vibration with IPA and TMDD. The experimental results indicated that the combination of ultrasonic agitation and surfactant additive (IPA&TMDD) could obtain a lower surface roughness of blazed plane in silicon echelle grating fabrication process.

Biointerface by Cell Growth on Graphene Oxide Doped Bacterial Cellulose/Poly(3,4-ethylenedioxythiophene) Nanofibers.

Highly biocompatible advanced materials with excellent electroactivity are increasingly meaningful to biointerfaces and the development of biomedicine. Herein, bacterial cellulose/poly(3,4-ethylene dioxythiophene)/graphene oxide (BC/PEDOT/GO) composite nanofibers were synthesized through the in situ interfacial polymerization of PEDOT with the doping of GO. The abundant free carboxyl and hydroxy groups offer the BC/PEDOT/GO film active functional groups for surface modification. We demonstrate the use of this composite nanofiber for the electrical stimulation of PC12 neural cells as this resultant nanofiber scaffold could closely mimic the structure of the native extracellular matrix (ECM) with a promoting cell orientation and differentiation after electrical stimulation of PC12 cells. It is expected that this biocompatible BC/PEDOT/GO material will find potential applications in biological and regenerative medicine.

Novel Cu@SiO2/bacterial cellulose nanofibers: Preparation and excellent performance in antibacterial activity.

The antibacterial composite based on bacterial cellulose (BC) was successfully prepared by in-situ synthesis of SiO2 coated Cu nanoparticles (Cu@SiO2/BC) and its properties were characterized. Its chemical structures and morphologies were evaluated by Fourier transformation infrared spectrum (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). The results demonstrated that the SiO2 coated Cu particles were well homogeneously precipitated on the surface of BC. The Cu@SiO2/BC was more resistant to oxidation than the Cu nanoparticles impregnated into BC (Cu/BC) and then Cu@SiO2/BC could prolong the antimicrobial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli).

Regenerated bacterial cellulose microfluidic column for glycoproteins separation.

To analysis and separate glycoproteins, a simple strategy to prepare regenerated bacterial cellulose (RBC) column with concanavalin A (Con A) lectin immobilized in microfluidic system was applied. RBC was filled into microchannel to fabricate RBC microcolumn after bacterial cellulose dissolved in NaOH-sulfourea water solution. Lectin Con A was covalently connected onto RBC matrix surface via Schiff-base formation. Lysozyme (non-glycoprotein) and transferrin (glycoprotein) were successfully separated based on their different affinities toward the immobilized Con A. Overall, the RBC microfluidic system presents great potential application in affinity chromatography of glycoproteins analysis, and this research represents a significant step to prepare bacterial cellulose (BC) as column packing material in microfluidic system. What is more, troublesome operations for lectin affinity chromatography were simplified by integrating the microfluidic chip onto a HPLC (High Performance Liquid Chromatography) system.

Three-Dimensional BC/PEDOT Composite Nanofibers with High Performance for Electrode-Cell Interface.

There is an increasing need to synthesize biocompatible nanofibers with excellent mechanical and electrical performance for electrochemical and biomedical applications. Here we report a facile approach to prepare electroactive and flexible 3D nanostructured biomaterials with high performance based on bacterial cellulose (BC) nanofibers. Our approach can coat BC nanofibers with poly(3,4-ethylenedioxythiophene) (PEDOT) by in situ interfacial polymerization in a controllable manner. The PEDOT coating thickness is adjustable by the monomer concentration or reaction time during polymerization, producing nanofibers with a total diameter ranging from 30 to 200 nm. This fabrication process also provides a convenient method to tune different parameters such as the average pore size and electrical conductivity on the demands of actual applications. Our experiments have demonstrated that the 3D BC/PEDOT nanofibers exhibit high specific surface area, excellent mechanical properties, electroactive stability, and low cell cytotoxicity. With electrical stimulation, calcium imaging of PC12 neural cells on BC/PEDOT nanofibers has revealed a significant increase in the percentage of cells with higher action potentials, suggesting an enhanced capacitance effect of charge injection. As an attractive solution to the challenge of designing better electrode-cell interfaces, 3D BC/PEDOT nanofibers promise many important applications such as biosensing devices, smart drug delivery systems, and implantable electrodes for tissue engineering.

Oxidation and degradation of graphitic materials by naphthalene-degrading bacteria.

Nowadays, biologically oxidizing graphitic materials is of great importance for practical applications as an eco-friendly and low-cost method. In this work, a bacterial strain is isolated from the contaminated soil in a graphite mine and its ability to oxidize graphite, graphene oxide (GO) and reduced graphene oxide (RGO) is confirmed. After being cultivated with bacteria, graphite is inhomogeneously oxidized, and moreover oxidized sheets exfoliated from graphite are detected in the medium. RGO shows a higher degree of oxidation compared to graphite owing to more original defects, while GO breaks into small pieces and becomes full of holes. Both the holes in GO and the exfoliated sheets from graphite caused by bacteria have a size of below 1 µm, in agreement with the size of bacterial cells. Besides, the preliminary mechanism of the bacterial oxidation is explored, suggesting that the contact between bacterial cells and materials promotes the oxidation of graphitic materials. The ability of naphthalene-degrading bacteria to oxidize and degrade the graphitic materials shows the potential for producing GO in an eco-friendly way and degrading carbon nanomaterials in the environment.

Preparation of N-doped graphene by reduction of graphene oxide with mixed microbial system and its haemocompatibility.

A steady, effective and environment friendly method of introducing nitrogen into graphene is by microbial reduction of graphene oxide with mixed microorganisms from the anode chamber of microbial fuel cells (MFC). Using this method, N-doped graphene is easily obtained under mild conditions and by simple treatment processes, with the N/C ratio reaching 8.14%. Various characterizations demonstrate that the as-prepared N-doped graphene has excellent properties and is comparable with, and in some aspects, even better than, pristine graphene (containing only elemental C) prepared by chemical methods. The N-doped graphene (mainly substitution of C in the plane of the graphene sheet) with uniform distribution of N was haemocompatible, nontoxic, and water-dispersible, all of which are desirable properties for biomaterials and attributable to a synergetic metabolic effect of mixed microorganisms.

Microbial oxidation of dispersed graphite by nitrifying bacteria 2011.2.

A facile and green microbial method to produce graphite oxide nanosheets and nanoparticles is described. The obtained graphite oxide nanosheets have few layers with 0.7-1.5 nm height and 50-300 nm size. The carbon nanoparticles possess the size of 20-60 nm and the height of 2-4 nm.