Low-triggering-potential electrochemiluminescence based on mental-organic frameworks encapsulation of ruthenium for synthetic cathinone detection by coupling photonic crystal light-scattering signal amplification of covalent-organic frameworks.

Developing effective electrochemiluminescence (ECL) platforms is always an essential concern in highly sensitive bioanalysis. In this work, a low-triggering-potential ECL sensor was designed for detecting synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV) based on a dual-signal amplification strategy. Initially, a probe was created by integrating Ruthenium into the hollow porphyrin-based MOF (PCN-222) structure to decrease the excitation potential and enhance ECL performance without external co-reaction accelerators. Additionally, for the first time, photonic crystals (PCs) assembled from covalent organic frameworks (COFs) were employed to amplify the ECL signal, thereby increasing the photon flux and the loading capacity of the ECL emitter to enhance sensitivity of the sensor. In the presence of the target MDPV, the aptamer labeled with Ferrocene (Fc) experienced conformational changes, causing Fc to approach the luminophore and resulting in ECL quenching. This effect was attributed to aptamer's conformational changes induced by the target, directly correlating with the target concentration. The constructed sensor showed good linearity with the target MDPV concentration, covering a dynamic range from 1.0 × 10-14 to 1.0 × 10-6 g/L and achieved an ultra-low detection limit of 4.79 × 10-15 g/L. This work employed dual amplification strategies to enhance ECL signals effectively, providing a novel method for developing highly responsive and bioactive sensors.

SMYD2-Methylated PPARγ Facilitates Hypoxia-Induced Pulmonary Hypertension by Activating Mitophagy.

BACKGROUND: Hyperproliferation of pulmonary arterial smooth muscle cells (PASMCs) and consequent pulmonary vascular remodeling are the crucial pathological features of pulmonary hypertension (PH). Protein methylation has been shown to be critically involved in PASMC proliferation and PH, but the underlying mechanism remains largely unknown. METHODS: PH animal models were generated by treating mice/rats with chronic hypoxia for 4 weeks. SMYD2-vTg mice (vascular smooth muscle cell-specific suppressor of variegation, enhancer of zeste, trithorax and myeloid Nervy DEAF-1 domain-containing protein 2 transgenic) or wild-type rats and mice treated with LLY-507 were used to investigate the function of SMYD2 (suppressor of variegation, enhancer of zeste, trithorax and myeloid Nervy DEAF-1 domain-containing protein 2) on PH development in vivo. Primary cultured rat PASMCs with SMYD2 knockdown or overexpression were used to explore the effects of SMYD2 on proliferation and to decipher the underlying mechanism. RESULTS: We demonstrated that the expression of the lysine methyltransferase SMYD2 was upregulated in the smooth muscle cells of pulmonary arteries from patients with PH and hypoxia-exposed rats/mice and in the cytoplasm of hypoxia-induced rat PASMCs. More importantly, targeted inhibition of SMYD2 by LLY-507 significantly attenuated hypoxia-induced pulmonary vascular remodeling and PH development in both male and female rats in vivo and reduced rat PASMC hyperproliferation in vitro. In contrast, SMYD2-vTg mice exhibited more severe PH phenotypes and related pathological changes than nontransgenic mice after 4 weeks of chronic hypoxia treatment. Furthermore, SMYD2 overexpression promoted, while SMYD2 knockdown suppressed, the proliferation of rat PASMCs by affecting the cell cycle checkpoint between S and G2 phases. Mechanistically, we revealed that SMYD2 directly interacted with and monomethylated PPARγ (peroxisome proliferator-activated receptor gamma) to inhibit the nuclear translocation and transcriptional activity of PPARγ, which further promoted mitophagy to facilitate PASMC proliferation and PH development. Furthermore, rosiglitazone, a PPARγ agonist, largely abolished the detrimental effects of SMYD2 overexpression on PASMC proliferation and PH. CONCLUSIONS: Our results demonstrated that SMYD2 monomethylates nonhistone PPARγ and inhibits its nuclear translocation and activation to accelerate PASMC proliferation and PH by triggering mitophagy, indicating that targeting SMYD2 or activating PPARγ are potential strategies for the prevention of PH.

The Benefits of Oral Glucose-Lowering Agents: GLP-1 Receptor Agonists, DPP-4 and SGLT-2 Inhibitors on Myocardial Ischaemia/Reperfusion Injury.

Myocardial infarction (MI) is a life-threatening cardiovascular disease that, on average, results in 8.5 million deaths worldwide each year. Timely revascularization of occluded vessels is a critical method of myocardial salvage. However, reperfusion paradoxically leads to the worsening of myocardial damage known as myocardial ischaemia/reperfusion injury (MI/RI). Therefore, reducing the size of myocardial infarction after reperfusion is critical and remains an important therapeutic goal. The susceptibility of the myocardium to MI/RI may be increased by diabetes. Currently, some traditional antidiabetic agents such as metformin reduce MI/RI by decreasing inflammation, inhibiting oxidative stress, and improving vascular endothelial function. This appears to be a new direction for the treatment of MI/RI. Recent cardiovascular outcome trials have shown that several oral antidiabetic agents, including glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl peptidase-4 inhibitors (DPP-4is), and sodium-glucose-linked transporter-2 inhibitors (SGLT-2is), not only have good antidiabetic effects but also have a protective effect on myocardial protection. This article aims to discuss the mechanisms and effects of oral antidiabetic agents, including GLP-1RAs, DPP-4is, and SGLT-2is, on MI/RI to facilitate their clinical application.

An electrochemiluminescence sensor based on Ag NPs amplifying PDDA-modified TbPO4:Ce NWs signal for sensitive detection of lincomycin.

The residue of lincomycin in water will not only aggravate the drug resistance of bacteria but also cause damage to the human body through biological accumulation. In this work, an electrochemiluminescence (ECL) aptasensor for the detection of lincomycin was constructed based on polydimethyldiallylammonium chloride (PDDA) functionalized Ce-doped TbPO4 nanowires (PDDA-TbPO4:Ce NWs) and silver nanoparticles (Ag NPs). TbPO4:Ce NWs were used as the luminophore, and PDDA was used to functionalize the luminophore to make the surface of the luminophore positively charged. The negatively charged silver nanoparticles were combined with PDDA-TbPO4:Ce NWs by electrostatic interaction. Ag NPs accelerated the electron transfer rate and promoted the ECL efficiency, which finally increased the ECL intensity of TbPO4:Ce NWs by about 4 times. Under the optimal conditions, the detection limit of the ECL sensor was as low as 4.37 × 10-16 M, and the linear range was 1 × 10 - 15 M to 1 × 10 - 5 M, with good selectivity, stability, and repeatability. The sensor can be applied to the detection of lincomycin in water, and the recovery rate is 97.7-103.4 %, which has broad application prospects.

SP2509 functions as a novel ferroptosis inhibitor by reducing intracellular iron level in vascular smooth muscle cells.

Previous studies have shown that ferroptosis of vascular smooth muscle cells (VSMCs) is involved in the development of aortic dissection (AD) and that histone methylation regulates this process. SP2509 acts as a specific inhibitor of lysine-specific demethylase 1 (LSD1), which governs a variety of biological processes. However, the effect of SP2509 on VSMC ferroptosis and AD remains to be elucidated. This aim of this study was to investigate the role and underlying mechanism of SP2509-mediated histone methylation on VSMC ferroptosis. Here, a mouse model of AD was established, and significantly reduced levels of H3K4me1 and H3K4me2 (target of SP2509) were found in the aortas of AD mice. In VSMCs, SP2509 treatment led to a dose-dependent increase in H3K4me2 levels. Furthermore, we found that SP2509 provided equivalent protection to ferrostatin-1 against VSMC ferroptosis, as evidenced by increased cell viability, decreased cell death and lipid peroxidation. RNA-sequencing analysis and subsequent experiments revealed that SP2509 counteracted cystine deficiency-induced response to inflammation and oxidative stress. More importantly, we demonstrated that SP2509 inhibited the expression of TFR and ferritin to reduce intracellular iron levels, thereby effectively blocking the process of ferroptosis. Therefore, our findings indicate that SP2509 protects VSMCs from multiple stimulus-induced ferroptosis by reducing intracellular iron levels, thereby preventing lipid peroxidation and cell death. These findings suggest that SP2509 may be a promising drug to alleviate AD by reducing iron deposition and VSMC ferroptosis.

A dual-mode biosensor based on silica inverse opal photonic crystals modulated electrochemiluminescence and dye displacement colorimetry for the sensitive detection of synthetic cathinone in water environment.

To address the challenges posed by signal capacity limitations and the reliance of sensing methods on single analytical information, this study developed an electrochemiluminescence (ECL) and colorimetric dual-mode sensing platform for the precise detection of 4-chloroethcathinone (4-CEC) in water environments. Firstly, the accurate alignment of the reflection wavelength of appropriately sized silica inverse opal photonic crystals (SIOPCs) with the ECL emission wavelength of luminescent metal-organic frameworks (PCN-224) has been achieved via diameter modulation. This innovative design, which cleverly utilized the band-edge effect, improved the luminous intensity of the ECL sensor, leading to a significant boost in analytical performance. Secondly, the establishment of a colorimetric detection method for confirming the presence of 4-CEC in samples through visual observation of color changes was achieved by employing an aptamer-based dye displacement reaction, utilizing differential binding affinities between the aptamer and both the sulforhodamine B (SRB) and 4-CEC. Under the optimal experimental conditions, the dual-mode sensor demonstrated ECL detection of limits (LOD) of 2.6 × 10-13 g/L and colorimetric LOD of 6.5 ng/L for 4-CEC. These findings highlighted the tremendous potential of developing streamlined and efficient dual-signal readout platforms using ECL aptamer sensors for the precise determination of other Synthetic cathinones (SCs) in water environments.

A zinc-air battery assisted self-powered electrochemical sensor for sensitive detection of microcystin-RR.

Building a high-performance sensing platform is the key to developing sensitive sensors. Herein, a highly sensitive self-powered electrochemical sensor (SPES) was constructed using a WO3·H2O film as the cathode prepared by a hydrothermal method and Zn as the anode, and it could be applied to sensitive detection of microcystin (MC-RR). The WO3·H2O film with a larger specific surface area could boost the oxygen reduction reaction (ORR), which could achieve signal amplification and significantly increase the sensitivity of the sensors. Under the optimal conditions, there was a good linear relationship between the increased electrical power density and the logarithm of MC-RR concentration with a detection limit of 1.31 × 10-15 M (S/N = 3). This method had good anti-interference ability and stability when applied to the determination of MC-RR content in actual samples, which could boost the potential application of electrochemical sensors in the field of environmental monitoring.

The lysine methyltransferase SMYD2 facilitates neointimal hyperplasia by regulating the HDAC3-SRF axis.

Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.

Regulated cell death in myocardial ischemia-reperfusion injury.

Myocardial ischemia-reperfusion (I/R) injury most commonly occurs in coronary artery disease when prompt reperfusion is used to salvage the ischemic myocardium. Cardiomyocyte death is a significant component of myocardial I/R injury and its mechanism was previously thought to be limited to apoptosis and necrosis. With the discovery of novel types of cell death, ferroptosis, necroptosis, and pyroptosis have been shown to be involved in myocardial I/R. These new forms of regulated cell death cause cardiomyocyte loss and exacerbate I/R injury by affecting reactive oxygen species (ROS) generation, calcium stress, and inflammatory cascades, subsequently mediating adverse remodeling, cardiac dysfunction, and heart failure. Herein, we review the roles of ferroptosis, necroptosis, and pyroptosis in myocardial I/R and discuss their contribution to pathology.

The functions of SET domain bifurcated histone lysine methyltransferase 1 (SETDB1) in biological process and disease.

Histone methyltransferase SETDB1 (SET domain bifurcated histone lysine methyltransferase 1, also known as ESET or KMT1E) is known to be involved in the deposition of the di- and tri-methyl marks on H3K9 (H3K9me2 and H3K9me3), which are associated with transcription repression. SETDB1 exerts an essential role in the silencing of endogenous retroviruses (ERVs) in embryonic stem cells (mESCs) by tri-methylating H3K9 (H3K9me3) and interacting with DNA methyltransferases (DNMTs). Additionally, SETDB1 is engaged in regulating multiple biological processes and diseases, such as ageing, tumors, and inflammatory bowel disease (IBD), by methylating both histones and non-histone proteins. In this review, we provide an overview of the complex biology of SETDB1, review the upstream regulatory mechanisms of SETDB1 and its partners, discuss the functions and molecular mechanisms of SETDB1 in cell fate determination and stem cell, as well as in tumors and other diseases. Finally, we discuss the current challenges and prospects of targeting SETDB1 for the treatment of different diseases, and we also suggest some future research directions in the field of SETDB1 research.

[Influence of wind, cold and dampness on clinical manifestation of knee osteoarthritis patients based on the stratifications of traditional Chinese medicine constitution].

OBJECTIVE: To explore influence of external factors of wind, cold and dampness on clinical symptoms in knee osteoarthritis (KOA) patients with different constitutions of traditional Chinese medicine. METHODS: A cross-sectional stratified study was performed to select 108 patients with GradeⅡKOA in Kellgren & Lawrence (K-L) classification, including 22 males and 86 females, aged from 47 to 75 years old with an average of (60.7±6.0) years old;body mass index(BMI) ranged from 17.87 to 31.22 kg·m-2 with an average of (23.80±2.86) kg·m-2. According to Classification and Judgment of TCM Physique (ZYYXH/T157-2009), the types of TCM physique were determined and divided into 4 layers according to the deficiency and actual physique. Among them, there were 24 patients without biased physique, 12 males and 12 females, aged from 51 to 73 years old with an average of(62.8±6.0) years old, BMI ranged from 17.87 to 31.14 kg·m-2 with an average of (24.32±3.25) kg·m-2;there were 46 patients with virtual bias constitution, including 7 males and 39 females, aged from 47 to 70 years old with an average of (60.0±5.8) years old, BMI ranged from 19.38 to 31.22 kg·m-2 with an average of(23.42±2.97) kg·m-2;There were 26 patients with solid bias constitution, including 2 males and 24 females, aged from 48 to 75 years old with an average of (60.4±5.8) years old, BMI ranged from 21.16 to 30.76 kg·m-2 with an average of (24.15±2.33) kg·m-2;there were 9 patients with special constitution, 1 male and 8 female, aged from 53 to 75 years old with an average of (59.8±7.5) years old, BMI ranged from 19.26 to 26.67 kg·m-2 with an average of (23.79±2.49) kg·m-2. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used to evaluate severity of clinical symptoms. The wind-cold-dampness external factor score was calculated through the questionnaire of wind-cold-dampness syndrome scale to evaluate degree of influence of wind-cold-dampness external factor. Pearson correlation analysis and partial correlation analysis were used to calculate the correlation coefficient between severity of external factors affecting wind, cold and dampness and severity of clinical symptoms in patients with different TCM constitution stratification. RESULTS: There was no statistical significance between total score of wind-cold-dampness and WOMAC score in patients with no biased constitution and special condition. Total wind-cold-dampness score of patients with virtual biased constitution was positively correlated with WOMAC stiffness score (r=0.327, P=0.032), and total wind-cold-dampness score of patients with solid biased constitution was positively correlated with WOMAC pain score (r=0.561, P=0.005) and WOMAC overall score (r=0.446, P=0.033). After further adjusting for the interaction of external factors of wind-cold-dampness, there was no statistical significance between wind-cold-dampness scores and WOMAC scores in patients with solid biased constitution. The score of dampness and pathogenic factors was positively correlated with WOMAC stiffness score (r=0.414, P=0.007). CONCLUSION: The external factors of wind-cold dampness have different effects on the clinical symptoms of KOA patients with different TCM constitutions. Compared with other constitutions, the rigid symptoms of patients with asthenic biased constitutions are more susceptible to dampness pathogenic factors.

Synergistic Multieffect Catalytic Amplified Cathodic Electrochemiluminescence Biosensor via Target Binding-Induced Aptamer Conformational Changes for the Ultrasensitive Detection of Synthetic Cathinone.

Signal amplification is a powerful approach to increasing the detection sensitivity of electrochemiluminescence (ECL). Here, we developed synergistic multieffect catalytic strategies based on CuCo2O4 nanorod combination of Ag NPs as coreaction accelerators to fabricate an efficient covalent organic framework (PTCA-COF)-based ternary ECL biosensor. Concretely, the high redox reversibility of Co3+/Co2+ and Cu2+/Cu+ would constantly promote the decomposition of S2O82- for ECL emission. Meanwhile, the introduction of Ag NPs with excellent electrocatalytic activity further realized multiple amplification of the ECL signal. Furthermore, the good hydrogen evolution reaction (HER) ability of Ag@CuCo2O4 nanorods could accelerate the proton transmission rate of the system to amplify ECL behavior. In the presence of the target synthetic cathinone 4-chloroethcathinone (4-CEC) as the quenching ECL signal-response probe, the Ferrocene (Fc)-labeled aptamer folded into the conformationally limited stem-loop structure, bringing Fc near the ECL luminophore and resulting in quenched ECL emission. The quenching effect was connected with target-induced aptamer conformational changes and consequently reflected the target concentration. Under optimum conditions, the proposed biosensor realized a highly sensitive assay for 4-CEC with a large dynamic range from 1.0 × 10-12 to 1.0 × 10-6 g/L and a detection limit as low as 2.5 × 10-13 g/L. This study integrated multiple amplification strategies for efficient ECL enhancement, which provided a novel approach to constructing highly bioactive and sensitive sensors.

A molecularly imprinted polypyrrole electrochemiluminescence sensor based on a novel zinc-based metal-organic framework and chitosan for determination of enrofloxacin.

Nowadays, bacterial resistance caused by the abuse of antibiotics has become a worldwide problem. In this work, a quinolone antibiotic, enrofloxacin (ENR), was rapidly monitored by combining a selective molecular imprinting polymer (MIP) with the electrochemiluminescence (ECL) method. Zn-PTC, a novel zinc-based metal-organic framework (MOF) that has a large specific surface area and ultra-high luminous efficiency, was used as the ECL luminophore. Chitosan (CHIT) was used to contact the specific surface area of molecularly imprinted polymer films and further improved the detection sensitivity. Subsequently, the molecularly imprinted polypyrrole was electropolymerized on the surface of the Zn-PTC and CHIT modified glassy carbon electrode (GCE). The specific sites that could target recombining ENR were shaped on the surface of MIP after extracting the ENR templates. The specific concentrations of ENR could be detected according to the difference in ECL intensity (ΔECL) between the eluting and rebinding of ENR. After optimization, a good linear response of ΔECL and a logarithm of specific ENR concentrations could be obtained in the range of 1.0 × 10-12-1.0 × 10-4 mol L-1, with a detection limit of 9.3 × 10-13 mol L-1 (S/N = 3). Notably, this study provided a rapid, convenient, and cheap method for the detection of ENR in actual samples.

Ultrasensitive electrochemiluminescence sensor for the detection of synthetic cannabinoids based on perovskite as coreaction accelerator and light-scattering effects of photonic crystals.

As is common knowledge, a strong electrochemiluminescence (ECL) signal is required to ensure the high sensitivity of trace target detection. Here, a dual signal amplification strategy by integrating of perovskite and photonic crystal was fabricated for quantitative synthetic cannabinoids (AB-PINACA) detection based on Zr-connected PTCA and TCPP (PTCA-TCPP) with excellent ECL performance as luminophores. On the one hand, the co-reaction accelerator perovskite (LaCoO3) improved the effective electroactive area of the electrode and promoted the decomposition of K2S2O8, resulting in a stronger ECL signal value. On the other hand, polystyrene inverse opal (PIOPCs) formed after the swelling of PS microspheres not only taken advantage of the light scattering effect and excellent catalytic property of photonic crystals to amplify the ECL signal, but also could be used as a binder to fix LaCoO3 and PTCA-TCPP on the electrode surface to generate unprecedented ECL response and stable ECL signals. Subsequently, the detection substance AB-PINACA was loaded on the electrode surface via the amide bond with the luminophores PTCA-TCPP, thus quenching the ECL signal, so as to realize the sensitive detection of synthetic cannabinoids. Under the optimal conditions, the proposed sensor achieved highly sensitive AB-PINACA detection with a dynamic range from 1.0 × 10-12 to 1.0 × 10-3 g/L and the detection limit was 1.1 × 10-13 g/L, which had great application potential in the detection of synthetic cannabinoids.

A metal-organic framework regulated graphdiyne-based electrochemiluminescence sensor with a electrocatalytic self-acceleration effect for the detection of di-(2-ethylhexyl) phthalate.

In this work, a super-sensitive electrochemiluminescence (ECL) aptamer sensor was constructed using a multiple signal amplification strategy to realize ultra-sensitive detection of di-(2-ethylhexyl) phthalate (DEHP). The incorporation of a highly efficient electrocatalytic metal-organic framework (NH2-Zr-MOF) and graphdiyne (GDY) composite has significantly enhanced the overall electrochemically active surface area, facilitating electron transfer during the entire electrochemical reaction process, and the large number of pores in graphdiyne and NH2-Zr-MOF limited a series of redox reactions within a certain range. This resulted in the generation of a greater number of SO4˙- radicals, thereby boosting the ECL intensity of the GDY in the K2S2O8 system. To increase the performance of the sensor even further, sodium ascorbate (NaAsc) as an accelerator was added to the co-reactant system. Additionally, nitrogen micro-nano bubbles with higher stability and stronger mass transfer have been introduced into the ECL system for the first time. Based on these, the aptamer as the recognition element realized the ultra-sensitive detection of DEHP in the linear range of 1.0 × 10-12 to 1.0 × 10-4 mg mL-1 with the limit of detection (LOD) of 2.43 × 10-13 mg mL-1. In summary, we have utilized the electrocatalytic activity of the porous MOF and the reducing capability of sodium ascorbate to enhance the ECL emission of GDY, which has been successfully applied to the detection of DEHP in water samples.

Novel inner filter effect-based near-infrared electrochemiluminescence sensor mediated by well-matched AgBr-nitrogen-doped Ti3C2 MXene and nonmetallic plasmon WO3•H2O.

The development of innovative and efficient strategy is of paramount importance for near-infrared (NIR) electrochemiluminescence (ECL) sensing, which can substantially promote ECL detection in a wide range of situations. Herein, the inner filter effect (IFE) strategy was designed to construct an ultrasensitive NIR ECL biosensor based on the well-matched AgBr nanocrystals (NCs) decorated nitrogen-doped Ti3C2 MXene nanocomposites (AgBr-N-Ti3C2) and hydrated defective tungsten oxide nanosheets (dWO3•H2O). Specifically, the AgBr-N-Ti3C2 nanocomposites displayed extremely effective NIR ECL emission because N-doping could accelerate electron transfer and boost the red-shift of the ECL spectrum. The nonmetallic plasmon dWO3•H2O was used as an absorber due to its facile tuning of the spectra overlap and higher molar extinction coefficients. Time-resolved emission decay curves proved that the decreased ECL intensity was ascribed to the IFE-based steady quenching mechanism. With the support of tetracycline (TC) aptamer and the complementary DNA chain, the fabricated NIR ECL-IFE biosensor performed a wide linear range of 100 nM âˆ¼ 10 fM with a low detection limit of 2.2 fM (S/N = 3), and it exhibited excellent stability, sensitivity, and reproducibility, so as to be applied to real samples. This strategy opens a new avenue to constructing an efficient NIR ECL-IFE system and shows excellent practical potential in actual sample analysis.

The roles of METTL3 on autophagy and proliferation of vascular smooth muscle cells are mediated by mTOR rather than by CDK1.

BACKGROUND: Aberrant proliferation of vascular smooth muscle cells (VSMCs) is the cause of neointima formation followed by vascular injury. Autophagy is involved in this pathological process, but its function is controversial. Recently, we found that methyltransferase like 3 (METTL3) inhibited VSMC proliferation by activating autophagosome formation. Moreover, we also demonstrated that METTL3 reduced the levels of phosphorylated mammalian target of rapamycin (p-mTOR) and cyclin dependent kinase 1 (p-CDK1/CDC2), which were critical for autophagy and proliferation regulation. However, whether mTOR and CDK1 mediated the function of METTL3 on autophagy and proliferation in VSMCs remains unknown. RESULTS: We showed that the activator of mTOR, MHY1485 largely reversed the effects of METTL3 overexpression on VSMC autophagy and proliferation. Rapamycin, the inhibitor of mTOR, obviously nullified the pro-proliferation effects of METTL3 knockdown by activating autophagy in VSMCs. Unexpectedly, mTOR did not contribute to the impacts of METTL3 on migration and phenotypic switching of VSMCs. On the other hand, by knockdown of CDK1 in VSMC with METTL3 deficiency, we demonstrated that CDK1 was involved in METTL3-regulated proliferation of VSMCs, but this effect was not mediated by autophagy. CONCLUSIONS: We concluded that mTOR but not CDK1 mediated the role of METTL3 on VSMC proliferation and autophagy.

A novel molecularly imprinting polypyrrole electrochemiluminescence sensor based on MIL-101-g-C3N4 for supersensitive determination of ciprofloxacin.

Ciprofloxacin (CIP), a quinolone antibiotic, was rapidly and sensitively detected by integrating the molecularly imprinted polymer (MIP) with an ultra-sensitive electrochemiluminescence (ECL) method. g-C3N4, a typical polymer semiconductor, exhibited outstanding ECL efficiency and excellent ECL stability after combining with an iron-based metal-organic framework (MIL-101). Subsequently, the molecularly imprinted polypyrrole was electropolymerized on the composites of MIL-101-g-C3N4 modified glassy carbon electrode (GCE). The specific sites that could target rebinding the CIP molecules were formed on the surface of MIP after extracting the CIP templates. The determination of specific concentrations of CIP could be realized according to the difference in ECL intensity (△ECL) between the eluting and rebinding of the CIP. Under optimal conditions, a good linear response of △ECL and the logarithm of CIP concentrations was obtained in the range 1.0 × 10-9 ~ 1.0 × 10-5 mol/L, with a detection limit of 4.5 × 10-10 mol/L (S/N = 3) (the working potential was -1.8 ~ 0 V). The RSD of all points in the calibration plot was less than 5.0% and the real samples recovery was between 98.0 and 104%. This paper displays satisfactory selectivity and sensitivity, providing a rapid, convenient, and cheap method for the determination of CIP in real samples.

Multi-stage adsorption of methyl orange on the nitrogen-rich biomass-derived carbon adsorbent: DFT and MD evaluation.

Dyes that are released into the environment may have negative effects on living organisms. To address this issue, a biomass-derived carbon adsorbent made from Enteromorpha was tested for its ability to remove methyl orange (MO) from wastewater. The adsorbent was found to be effective in removing MO, with a 1:4 impregnation ratio producing an adsorbent that could remove 96.34% of MO from a 200 mg/L solution using only 0.1 g of adsorbent. At higher concentrations, the adsorption capacity increased up to 269.58 mg/g. Through molecular dynamics simulations, it was discovered that after mono-layer adsorption reached saturation, the remaining MO molecules in solution formed hydrogen bonds with the adsorbed MO, which led to further aggregation on the adsorbent surface and increased adsorption capacity. Additionally, theoretical investigations revealed that the adsorption energy of anionic dyes increased with Nitrogen-doped carbon materials, with the pyrrolic-N site having the highest adsorption energy for MO. The carbon material derived from Enteromorpha showed promise in treating wastewater containing anionic dyes, thanks to its high adsorption capacity and strong electrostatic interaction with the sulfonic acid groups of MO.

Histone acetyltransferase P300 deficiency promotes ferroptosis of vascular smooth muscle cells by activating the HIF-1α/HMOX1 axis.

BACKGROUND: E1A-associated 300-kDa protein (P300), an endogenous histone acetyltransferase, contributes to modifications of the chromatin landscape of genes involved in multiple cardiovascular diseases. Ferroptosis of vascular smooth muscle cells (VSMCs) is a novel pathological mechanism of aortic dissection. However, whether P300 regulates VSMC ferroptosis remains unknown. METHODS: Cystine deprivation (CD) and imidazole ketone erastin (IKE) were used to induce VSMC ferroptosis. Two different knockdown plasmids targeting P300 and A-485 (a specific inhibitor of P300) were used to investigate the function of P300 in the ferroptosis of human aortic smooth muscle cells (HASMCs). Cell counting kit-8, lactate dehydrogenase and flow cytometry with propidium iodide staining were performed to assess the cell viability and death under the treatment of CD and IKE. BODIPY-C11 assay, immunofluorescence staining of 4-hydroxynonenal and malondialdehyde assay were conducted to detect the level of lipid peroxidation. Furthermore, co-immunoprecipitation was utilized to explore the interaction between P300 and HIF-1α, HIF-1α and P53. RESULTS: Compared with normal control, the protein level of P300 was significantly decreased in HASMCs treated with CD and IKE, which was largely nullified by the ferroptosis inhibitor ferrostatin-1 but not by the autophagy inhibitor or apoptosis inhibitor. Knockdown of P300 by short-hairpin RNA or inhibition of P300 activity by A-485 promoted CD- and IKE-induced HASMC ferroptosis, as evidenced by a reduction in cell viability and aggravation of lipid peroxidation of HASMCs. Furthermore, we found that hypoxia-inducible factor-1α (HIF-1α)/heme oxygenase 1 (HMOX1) pathway was responsible for the impacts of P300 on ferroptosis of HASMCs. The results of co-immunoprecipitation demonstrated that P300 and P53 competitively bound HIF-1α to regulate the expression of HMOX1. Under normal conditions, P300 interacted with HIF-1α to inhibit HMOX1 expression, while reduced expression of P300 induced by ferroptosis inducers would favor HIF-1α binding to P53 to trigger HMOX1 overexpression. Furthermore, the aggravated effects of P300 knockdown on HASMC ferroptosis were largely nullified by HIF-1α knockdown or the HIF-1α inhibitor BAY87-2243. CONCLUSION: Thus, our results revealed that P300 deficiency or inactivation facilitated CD- and IKE-induced VSMC ferroptosis by activating the HIF-1α/HMOX1 axis, which may contribute to the development of diseases related to VSMC ferroptosis.