Mechanism of flavonoids in the treatment of gouty arthritis (Review).

The present review expounds the advancements in the application and mechanisms of flavonoids in gouty arthritis, highlighting their significance in managing the disease. Gouty arthritis is among the most common and severe inflammatory diseases, caused by hyperuricemia and the deposition of sodium urate crystals in the joints and surrounding tissues, posing a serious threat to human life and health. Flavonoids, extracted from various herbs, have attracted significant attention due to their efficacy in improving gouty arthritis. The present study systematically reviews the in vivo studies and in vitro animal studies on flavonoids from herbal medicines for the treatment of gouty arthritis that have been previously published in the PubMed, ScienceDirect, Google Scholar and China National Knowledge Infrastructure databases between 2000 and 2023. The review of the literature indicated that flavonoids can improve gouty arthritis through multiple mechanisms. These include lowering xanthine oxidase activity, inhibiting uric acid (UA) synthesis, regulating UA transporters to promote UA excretion, reducing the inflammatory response and improving oxidative stress. These mechanisms predominantly involve regulating the NOD­like receptor 3 inflammasome, the Toll­like receptor 4/myeloid differentiation factor 88/nuclear factor­κB signaling pathway, and the levels of UA transporter proteins, namely recombinant urate transporter 1, glucose transporter 9, organic anion transporter (OAT)1 and OAT3. Various flavonoids used in traditional Chinese medicine hold therapeutic promise for gouty arthritis and are anticipated to pave the way for novel pharmaceuticals and clinical applications.

Mechanism of DaiTongXiao in the treatment of gouty arthritis through the NLRP3 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: DaiTongXiao (DTX) is a traditional Chinese Dai folk formulation utilized for gouty arthritis treatment, with substantial evidence supporting its anti-inflammatory properties. The NLRP3 inflammasome disorder is tightly linked to the development of many inflammatory diseases. AIM OF THE STUDY: To elucidate the therapeutic efficacy of DTX in gouty arthritis and reveal its potential underlying mechanism. MATERIALS AND METHODS: The primary active constituents in DTX were determined through ultraviolet spectrophotometry and gas chromatography. Rats underwent induction with monosodium urate (MSU), followed by treatment of J774A.1 cells with adenosine triphosphate (ATP) activation and lipopolysaccharide (LPS) induction and the subsequent culture in Dulbecco's modified Eagle's medium. The degree of foot joint swelling in rats was assessed, and ankle joints were evaluated through H&E staining. Enzyme-linked immunosorbent assay was performed to measure the levels of interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor (TNF)-α in both serum and cells. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to determine the relative mRNA expression levels of NLRP3, ASC, Caspase-1, and NF-κB in J774A.1 macrophages. The expression of NLRP3, ASC, Caspase-1, and NF-κB was examined by western blotting. RESULTS: DTX could alleviate MSU-induced joint swelling in rats, as evidenced by a reduction in joint inflammation. Moreover, DTX effectively enhanced the survival rate of J774A.1 cells following LPS induction and ATP activation. Furthermore, DTX significantly reduced IL-1ß, IL-6, IL-8, and TNF-α levels in both cell culture medium and rat serum. RT-PCR results revealed that DTX notably downregulated the mRNA expression levels of NLRP3, ASC, Caspase-1, and NF-κB in J774A.1 cells. Additionally, DTX downregulated NLRP3, ASC, NF-κB, and Caspase-1 expression in the joint tissue. CONCLUSIONS: DTX exerts a significant anti-gouty arthritis effect, with its mechanism being tightly linked to the NLRP3 inflammatory signaling pathway. This pathway may be modulated by inhibiting IL-1ß differentiation and maturation by downregulating NLRP3, ASC, Caspase-1, and NF-κB protein expression. This, in turn, leads to a reduction in the release of IL-6, IL-8, and TNF-α, ultimately impeding gouty arthritis progression.

Revealing the crystal facet effect on N2O formation during the NH3-SCR over α-MnO2 catalysts.

The detailed atomic-level mechanism of the effect induced by engineering the crystal facet of α-MnO2 catalysts on N2O formation during ammonia-selective catalytic reduction (NH3-SCR) was ascertained by combining density functional theory (DFT) calculations and thermodynamics/kinetic analysis. The surface energies of α-MnO2 with specific (100), (110), and (310) exposed planes were calculated, and the adsorptions of NH3, NO, and O2 on three surfaces were analyzed. The adsorption energies showed that NH3 and NO molecules could be strongly adsorbed on the surface of the α-MnO2 catalyst, while the adsorption of O2 was weak. Moreover, the key steps in the oxidative dehydrogenation of NH3 and the formation of NH2NO as well as dissociation of NH2 were studied to evaluate the catalytic ability of NH3-SCR reaction and N2 selectivity. The results revealed that the α-MnO2 catalyst exposed with the (310) plane exhibited the best NH3-SCR catalytic performance and highest N2 selectivity, mainly due to its low energy barriers in NH3 dehydrogenation and NH2NO generation, and difficulty in NH2 dissociation. This study deepens the comprehension of the facet-engineering of α-MnO2 on inhibiting N2O formation during the NH3-SCR, and points out a strategy to improve their catalytic ability and N2 selectivity for the low-temperature NH3-SCR process.

An Amplitude-Modulated Metadevice with Switchable Reflection, Transmission, and Absorption.

In this paper, we propose a reconfigurable metadevice with independent polarization control based on a 90° rotationally symmetric microstructure. Three functionalities of broadband high-efficiency transmission, broadband high-efficiency reflection, and perfect absorption are switched by the on-state and off-state PIN diodes. Coding metadevices designed with diversified lumped element combinations are further studied in detail. By controlling the two diodes on the top layer in opposite states, absorption bandwidth is significantly improved. Reasonable arrangements of coding sequences allow for reflected dual/multi-beam modulation. Electric field distribution, power loss, complex impedance functions, and equivalent circuit models are used to better analyze the physical mechanism of the design. A prototype of the microstructure has been fabricated, and the experimental results agree well with the simulation. Electronic components integrated microstructures with high degrees of freedom have potential applications in intelligent wireless communication, electronic detection, advanced sensors, and smart stealth radomes.

Mid-infrared reconfigurable all-dielectric metasurface based on Ge2Sb2Se4Te1 phase-change material.

In this paper, a reconfigurable all-dielectric metasurface based on Ge2Sb2Se4Te1 (GSST) phase-change material is proposed. By changing GSST from amorphous state to crystalline state, the metasurface can achieve high circular dichroism (CD) and wideband polarization conversion for circularly polarized waves in the mid-infrared (MIR) band. The maximum CD value reaches 0.95 at 74 THz, and circular polarization conversion efficiency is more than 90% in the wideband range of 41 THz - 48 THz. In addition, based on Pancharatnam-Berry phase, three kinds of wavefront manipulation of light have been realized: abnormal refraction, orbital angular momentum vortex beam and orbital angular momentum vortex beam splitting. This work has potential applications in the future MIR optical integrated system.

Development of a STandard reporting guideline for Evidence briefs for Policy (STEP): context and study protocol.

BACKGROUND: Evidence briefs for policy (EBP) draw on best-available data and research evidence (e.g., systematic reviews) to help clarify policy problems, frame options for addressing them, and identify implementation considerations for policymakers in a given context. An increasing number of governments, non-governmental organizations and research groups have been developing EBP on a wide variety of topics. However, the reporting characteristics of EBP vary across organizations due to a lack of internationally accepted standard reporting guidelines. This project aims to develop a STandard reporting guideline of Evidence briefs for Policy (STEP), which will encompass a reporting checklist and a STEP statement and a user manual. METHODS: We will refer to and adapt the methods recommended by the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network. The key actions include: (1) developing a protocol; (2) establishing an international multidisciplinary STEP working group (consisting of a Coordination Team and a Delphi Panel); (3) generating an initial draft of the potential items for the STEP reporting checklist through a comprehensive review of EBP-related literature and documents; (4) conducting a modified Delphi process to select and refine the reporting checklist; (5) using the STEP to evaluate published policy briefs in different countries; (6) finalizing the checklist; (7) developing the STEP statement and the user manual (8) translating the STEP into different languages; and (9) testing the reliability through real world use. DISCUSSION: Our protocol describes the development process for STEP. It will directly address what and how information should be reported in EBP and contribute to improving their quality. The decision-makers, researchers, journal editors, evaluators, and other stakeholders who support evidence-informed policymaking through the use of mechanisms like EBP will benefit from the STEP. Registration We registered the protocol on the EQUATOR network. ( https://www.equator-network.org/library/reporting-guidelines-under-development/#84 ).

DSN/TdT recycling digestion based cyclic amplification strategy for microRNA assay.

Sensitive and specific detection of microRNAs (miRNAs) is of great significance for early cancer diagnosis. Here we report a simple and sensitive fluorescence signal amplification strategy that based on DSN/TdT recycling digestion for miRNA detection. DSN initiates DNA digestion on 3'-phosphate-primer/miRNA heteroduplex which causes miRNA recycle. The digested DNA strands with 3'-OH ends enable TdT to synthesize a polydeoxyguanylic tails on the 3'-end. The DNAs with polydeoxyguanylic tails are converted to double-stranded-DNA prior to initiation of DSN/TdT recycling digestion. With the cooperation of TdT and DSN, a new round of digestion and extension is triggered, leading to massive fluorophores separating and signal amplification. The amplification strategy produces large amounts of 3'-OH probes that can be used directly for dsDNA enrichment and DSN digestion. Moreover, both DSN digestion and TdT extension are sequence-independent reaction without the need of complex sequences design. In addition, this strategy is utilized to analyze miRNA samples from MCF-7 cell lysates and Cu (II) ion samples, indicating its potential application in actual sample analysis. The method shows a promising analytical platform for DNA nicking-related studies and tumor biomarkers measuring in clinical diagnostics.

Telomerase-triggered DNAzyme spiders for exponential amplified assay of cancer cells.

A highly flexible electrochemical assay based on target-triggered DNAzyme spiders was proposed for the detection of telomerase. The DNAzyme-telomerase substrate primers (D-TSP) containing Cu2+-dependent DNAzymes serve as recognition elements, and primers of telomerase. Telomerase extracted from Hela cells recognize the D-TSP and elongated with DNA sequence repeats. A synthetic telomerase product hybridized with scaffold sequences of two DNAzyme-tethered probes on the basis of the mechanism of the proximity-ligation assay. The three-leg DNAzyme spiders has been assembled and initiated the autonomous hybridization/nicking/displacement cycles on substrate modified surface. The cleaved ferrocene-labeled fragements are adsorbed on gold surface leading to an increase in the electrochemical signal. As a result, the one input target, telomerase, release large amount of ferrocene-labeled DNA strands, achieving an exponential signal amplification and an excellent improvement in sensitivity over single molecule or two-component 'sandwich' binding complexes. Our proposed biosensor showed a nonlinear dependence with Hela cell numbers, ranging from 25 to 2000 with a detection limit of 10 cells. Telomerase activities from different cell lines were also successfully evaluated. Our electrochemical strategy based on target-triggered DNAzyme spiders was enzyme-free, PCR-free, simple in operation which indicated that it expected to expand the scope of DNA nanotechnology in the areas of clinical diagnosis.

Three Dimensional Multipod Superstructure based on Cu(OH)2 as a Highly Efficient Nanozyme.

A highly efficient nanozyme system, termed hollow multipod Cu(OH)2 superstructure (HMPS), has been developed via direct conversion from irregular nanoparticles. The HMPS displayed body size around 150 nm and branch lengths in the range of 150~250 nm. Based on the excellent catalytic property of HMPS, we developed a simple and highly sensitive colorimetric assay to detect urine glucose, and the results are in good agreement with hospital examination reports.

Cleaved DNAzyme substrate induced enzymatic cascade for the exponential amplified analysis of L-histidine.

A novel strategy of cleaved DNAzyme substrate induced enzymatic cascade has been devised for the exponential amplified detection of L-histidine. The enzyme strand carries out hydrolytic cleavage of the substrate strand in the presence of L-histidine. The cleaved DNAzyme substrates introduce the polymerase/endonuclease reaction cycles as primers. The L-histidine acts as the activator for enzymatic cascade amplification generating a distinguishable fluorescence enhancement. A good nonlinear correlation (R=0.9994) between fluorescence intensity and the logarithm of the L-histidine concentration is obtained over the range from 50 nM to 1.0 mM. The detection limit was estimated as 30 nM. This efficient amplification of the fluorescence signal is attributed to the L-histidine induced cooperation of Klenow Fragment polymerase (exo(-)) and Nb.BbvCI endonuclease reaction. The activation of such enzymatic cascades through analyte-DNAzyme interactions has a substantial impact on the development of exponential amplified DNAzyme sensors.

Enzymatic cascade based fluorescent DNAzyme machines for the ultrasensitive detection of Cu(II) ions.

A novel enzymatic cascade based fluorescent DNAzyme machine has been developed for the amplified detection of copper (Cu(2+)) ions. This is the first attempt to carry out the combination of the self-cleaving DNAzyme and the polymerase/endonuclease reaction cycles involving cleaved substrate extension. In the presence of Cu(2+) ions, the enzyme strand carries out catalytic reactions to hydrolytic cleavage of the substrate strand. The cleaved DNAzyme substrates act as primers and trigger the Klenow Fragment polymerization. Nb.BbvCI endonuclease cuts the double-stranded niking site and thus opens a new site for a new replication. The replication regenerates the complete dsDNA to initiate another cycle of nicking, polymerization and displacement. Finally the fluorescence dye, SG, inserts into the DNA double helix to generate a distinguishable fluorescence enhancement. The Cu(2+) ions act as the activator for enzymatic cascade amplification generating multiple duplex structures in the nascent product. An increasing fluorescence is observed with increasing Cu(2+) ions concentration. A good nonlinear correlation (R=0.9997) was obtained between fluorescence intensity and the cubic logarithm of the Cu(2+) ions concentration over the range 0.50-200 nM. This nonlinear response phenomenon results in an efficient improvement of the sensitivity of our current proposed assay. The activation of such enzymatic cascades through analyte-DNAzyme interactions is not only valuable to activate the cooperation of enzyme networks, but also has a substantial impact on the development of amplified DNAzyme sensors.

Epidemiological profile of hospitalised injuries among electric bicycle riders admitted to a rural hospital in Suzhou: a cross-sectional study.

Police reports indicate an increasing burden of electric bike (E-bike) casualties in China; however, hospitalised injury data have not been reported. The aim of the present work was to describe hospitalised injury patterns for E-bikers involved in road crashes and explore injury risk disparities among them. For the period October 2010 to April 2011, this cross-sectional study retrospectively collected information for hospitalised E-bikers involved in road crashes from hospital records, in Suzhou China, using the International Classification of Diseases, 10th revision (ICD-10) injury diagnosis codes. Injury nature and body region were further categorised using ICD-10 codes. Multivariate logistic regression was used to assess the risk of specific injury types. We found that hospitalised E-biker injuries (n=323) accounted for 57.2% of road traffic hospitalisations over the 6-month study period. The average age, length of stay and hospitalisation cost were 43.8 years, 10.0 days and ¥8229 (US$1286), respectively. Fractures and head injuries were common. The odds of traumatic brain injuries were significantly elevated for night-time E-bike crashes and incidents other than colliding with motor vehicles. These findings confirm E-bike injuries as an important population health problem and identify elevated injury odds in different E-biker groups. Future injury prevention initiatives should include encouraging helmet use among E-bikers.

Electrochemical aptameric sensor based on the Klenow fragment polymerase reaction for cocaine detection.

An electrochemical aptasensor based on Klenow fragment (KF) polymerase reaction that combines the aggregation of ferrocene-functionalized oligonucleotide has been developed successfully for cocaine detection. In the presence of cocaine, the recognition probe changed its hairpin conformation into the tripartite complex. The aptamer-cocaine complex gave a 3'-single-stranded tail sequence complementary to the surface-tethered capture probe. In KF polymerase reaction, the recognition probe served as a template for the extension of a capture probe. It requires a sample volume of 2 µL and is complete within 1 h. The ferrocene-appended oligonucleotide incorporated into the newly synthesized complementary probe leads to an electrochemical response. This sensitive detection of cocaine is due to a very low background signal and large signal enhancement up to 9-fold upon addition of analyte. It permits detection of as low as 200 µM cocaine. The simple and isothermal procedure does not require thermal cycling or special laboratory conditions, which makes it adaptable to low-cost and robust biosensing.

Biocatalytic growth of gold agglomerates on an electrode for aptamer-based electrochemical detection.

Here we describe the biocatalytic growth of high-density gold agglomerates on a gold electrode surface to form a carrier for aptamer probe immobilization. The present approach provides a simple strategy to promote the seed-mediated deposition of Au from AuCl(4)(-) onto surface-attached 12 nm diameter Au nanoparticles (AuNPs) in the presence of reductive coenzyme and surfactant. The growth process was studied by electrochemical impedance spectroscopy (EIS) and scanning electron microscopy (SEM). This nanostructured platform is effective and prospective toward the aptamer probe immobilization. For the nice performance of enhanced substrate, the aptamer-sensing interface showed excellent applicability under the investigations such as alternating current voltammetry (ACV) and surface-enhanced Resonance Raman scattering (SERRS) spectra.

Fluorescence aptameric sensor for strand displacement amplification detection of cocaine.

A new fluorescence method based on aptamer-target interactions has been developed for cocaine detection with target-induced strand displacement. Here we describe new probes, the hairpin-probe and the single strand-probe (ss-probe), that possess two recognition sequences of cocaine aptamer. In the presence of cocaine, both probes would associate with the target to form a tripartite complex. The conformational change in the hairpin-probe causes the opening of a hairpin structure and the hybridization to primer. With polymerase and the dNTPs, the replication of the single-stranded domain of hairpin-probe triggers the process of primer extension. When the hairpin-probe is converted into a fully double-stranded form, the ss-probe and cocaine are displaced to bind another hairpin-probe and initiate new amplification cycles. Fluorescence signal generation would be observed upon SYBR Green I intercalating into the new DNA double helix. The new protocol design permits detection of as low as 2 nM cocaine in a closed tube, offering a convenient approach for a homogeneous assay. Compared with previously reported cocaine aptameric sensors, our new method is highly sensitive, selective, and economical.

Fluorescence aptasensor based on competitive-binding for human neutrophil elastase detection.

To our knowledge, we report the first fluorescence aptasensor for detecting human neutrophil elastase (HNE) in homogeneous solution. The biosensor contains a short DNA scrambled sequence strand (SS) complementary to part of the aptamer sequence or the loop of molecular beacon (MB). The aptamer-HNE recognition event involves competition between the molecular beacon and loose HNE aptamer for the binding the short DNA strand. The new biosensor can detect as little as 0.34nM of HNE, and the response is linear in the tested concentration range of 0.34-68nM with the detection limit of 47pM.

[Preliminary discussion on the theory of body physiognomy in the Huangdineijing (Huangdi's Inner Classic)].

There are so many discussions on the body physiognomy in Huangdineijing (Huangdi's Inner Classic) that include not only the description of both difference of body physiognomy and its reasons, but also the discussions on physiological and pathological characteristics of different body physiognomy traits. Different physiological and pathological characteristics lead to different applicable therapeutic methods, so that Huangdineijing discusses the applicable therapeutic methods to different body physiognomy characteristics, especially elaborating on the difference between applicable acupuncture manipulation to those characteristics. Contents such as the above form the embryonic form of the theory of body physiognomy in Traditional Chinese Medicine (TCM).

Novel fluorescence enhancement IgE assay using a DNA aptamer.

In this paper, we demonstrate a fluorescence immunoglobulin E (IgE) assay probe based on a DNA aptamer. A Texas red-labeled short DNA strand (T-DNA) complementary with part of the IgE aptamer sequence was used to produce the fluorescence enhancement effected upon the binding of IgE to the aptamer. Another short DNA strand labeled with dabcyl quencher (Q-DNA) complementary with part of the aptamer sequence nearby the T-DNA location was used to lower the background fluorescence. The IgE can be detected in the concentration range from 9.2 x 10(-11) to 3.7 x 10(-8) mol L(-1) with a detection limit of 5.7 x 10(-11) mol L(-1).