[Effect of 2-phenylethyl-beta-glucopyranoside isolated from Huaizhong No. 1 Rehmannia glutinosa on hypoxic pulmonary hypertension by regulating PI3K/Akt/m TOR/HIF-1α pathway].

The study investigated the protective effect and mechanism of 2-phenylethyl-beta-glucopyranoside(Phe) from Huaizhong No.1 Rehmannia glutinosa on hypoxic pulmonary hypertension(PH), aiming to provide a theoretical basis for clinical treatment of PAH. Male C57BL/6N mice were randomly divided into normal group, model group, positive drug(bosentan, 100 mg·kg~(-1)) group, and low-and high-dose Phe groups(20 and 40 mg·kg~(-1)). Except for the normal group, all other groups were continuously subjected to model induction in a 10% hypoxic environment for 5 weeks, with oral administration for 14 days starting from the 3rd week. The cardiopulmonary function, right ventricular pressure, cough and asthma index, lung injury, cell apoptosis, oxidative stress-related indicators, immune cells, and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/hypoxic inducible factor 1α(HIF-1α) pathway-related proteins or mRNA levels were examined. Furthermore, hypoxia-induced pulmonary arterial smooth muscle cell(PASMC) were used to further explore the mechanism of Phe intervention in PH combined with PI3K ago-nist(740Y-P). The results showed that Phe significantly improved the cardiopulmonary function of mice with PH, decreased right ventricular pressure, cough and asthma index, and lung injury, reduced cell apoptosis, oxidative stress-related indicators, and nuclear levels of phosphorylated Akt(p-Akt) and phosphorylated mTOR(p-mTOR), inhibited the expression levels of HIF-1α and PI3K mRNA and proteins, and maintained the immune cell homeostasis in mice. Further mechanistic studies revealed that Phe significantly reduced the viability and migration ability of hypoxia-induced PASMC, decreased the expression of HIF-1α and PI3K proteins and nuc-lear levels of p-Akt and p-mTOR, and this effect was blocked by 740Y-P. Therefore, it is inferred that Phe may exert anti-PH effects by alleviating the imbalance of oxidative stress and apoptosis in lung tissues and regulating immune levels, and its mechanism may be related to the regulation of the PI3K/Akt/mTOR/HIF-1α pathway. This study is expected to provide drug references and research ideas for the treatment of PH.

Visible Light-Induced, Nickel-Catalyzed Late-Stage 4-Alkylation of Hantzsch Esters with Alkyl Bromide.

Herein, visible light-induced, nickel-catalyzed direct functionalization of the Hantzsch esters (HEs) with readily accessible alkyl bromides has been successfully achieved by taking advantage of HE as the reductant and substrate through an aromatization-dearomatization process. In this strategy, the single electron reduction of alkyl bromides by reactive Ni(I) species is essential for the success of this late-stage transformation. A wide range of 4-alkyl-1,4-dihydropyridines were rapidly assembled in moderate to good yields under mild conditions, rendering this photoinduced approach attractive for synthetic and medicinal chemistry.

Serum PYCARD may become a new diagnostic marker for rheumatoid arthritis patients.

BACKGROUND: The objective of this investigation is to analyze the levels and clinical relevance of serum PYCARD (Pyrin and CARD domain-containing protein, commonly known as ASC-apoptosis-associated speck-like protein containing a caspase activation and recruitment domain), interleukin-38 (IL-38), and interleukin-6 (IL-6) in individuals afflicted with rheumatoid arthritis (RA). METHODS: Our study comprised 88 individuals diagnosed with RA who sought medical attention at the Affiliated Hospital of Chengde Medical University during the period spanning November 2021 to June 2023, constituting the test group. Additionally, a control group of 88 individuals who underwent health assessments at the same hospital during the aforementioned timeframe was included for comparative purposes. The study involved the assessment of IL-38, IL-6, PYCARD, anti-cyclic citrullinated peptide antibody (anti-CCP), and erythrocyte sedimentation rate (ESR) levels in both groups. The research aimed to explore the correlations and diagnostic efficacy of these markers, employing pertinent statistical analyses for comprehensive evaluation. RESULTS: The test group had higher expression levels of PYCARD, IL-6, and IL-38 than the control group (P < 0.05). Based on the correlation analysis, there was a strong relationship between PYCARD and IL-38 (P < 0.01). The receiver operating characteristic (ROC) curve analysis revealed area under the curve (AUC) values of 0.97, 0.96, and 0.96 when using combinations of PYCARD and anti-CCP, IL-38 and anti-CCP, and IL-6 and anti-CCP for predicting RA, respectively. Importantly, all three of these pairs demonstrated superior AUC values compared to PYCARD, IL-38, IL-6, ESR, or anti-CCP used as standalone diagnostic indicators. CONCLUSION: PYCARD, IL-6, and IL-38 exhibit promising potential as novel diagnostic markers and may constitute valuable tools for supporting the diagnosis of RA.

Photoredox/Nickel Dual Catalysis-Enabled Aryl Formylation with 2,2-Dimethoxy-N,N-dimethylethan-1-amine as CO Source.

Herein, a dual photoredox/nickel catalyzed formylation of aryl bromide with commercially available 2,2-dimethoxy-N,N-dimethylethan-1-amine as an effective CO source has been successfully achieved, delivering a series of aromatic aldehydes in moderate to good yields. Compared with the traditional reductive carbonylation process, this newly designed synthetic protocol provides a straightforward toolbox to access aromatic aldehydes, obviating the use of carbon monoxide and stoichiometric reductants. Finally, the utility of this direct formylation reaction was demonstrated in the pharmaceutical analogue synthesis.

Nanosensor detection of reactive oxygen and nitrogen species leakage in frustrated phagocytosis of nanofibres.

Exposure to widely used inert fibrous nanomaterials (for example, glass fibres or carbon nanotubes) may result in asbestos-like lung pathologies, becoming an important environmental and health concern. However, the origin of the pathogenesis of such fibres has not yet been clearly established. Here we report an electrochemical nanosensor that is used to monitor and quantitatively characterize the flux and dynamics of reactive species release during the frustrated phagocytosis of glass nanofibres by single macrophages. We show the existence of an intense prolonged release of reactive oxygen and nitrogen species by single macrophages near their phagocytic cups. This continued massive leakage of reactive oxygen and nitrogen species damages peripheral cells and eventually translates into chronic inflammation and lung injury, as seen during in vitro co-culture and in vivo experiments.

GAS5 promotes cytarabine induced myelosuppression via inhibition of hematopoietic stem cell differentiation.

Cytarabine (Ara-C) is widely used in the induction chemotherapy for acute myeloid leukemia (AML). Association between LncRNA GAS5 genetic polymorphism and the recovery of hematopoietic function after Ara-C-based chemotherapy is observed. This study aimed to identify whether intervention of GAS5 expression and GAS5 genotype affect Ara-C-induced inhibition of hematopoietic stem cells (HSCs) differentiation. In this study, cord blood-derived CD34+ cells were cultured in vitro, and a cell model of myelosuppression was established by treatment of CD34+ cells with Ara-C. The effect of GAS5 overexpression, Ara-C treatment, and GAS5 rs55829688 genotype on the hematopoietic colony-forming ability of CD34+ cells was assessed using methylcellulose-based colony forming unit assay. GAS5 overexpression slowed down the proliferation of cord blood-derived CD34+ cells significantly (p < 0.05) and decreased their ability to form hematopoietic colonies in vitro. Ara-C significantly reduced the hematopoietic colony-forming ability of CD34+ cells in vitro (p < 0.0001), and overexpressing GAS5 further decreased the number of hematopoietic colonies. GAS5 expression was higher in CD34+ cells than in CD34- cells, and positively correlated with GATA1 mRNA expression in CD34+ cells in vitro culture. However, GAS5 genotype had no effect on the total number of hematopoietic colonies formed from cord blood-derived CD34+ cells. In conclusion, our study highlights that GAS5 inhibited the in vitro proliferation and reduced the hematopoietic colony-forming ability of cord blood-derived CD34+ cells, with the most pronounced effect observed on CFU-GEMM formation. GAS5 also enhanced the inhibitory effect of Ara-C on the in vitro hematopoietic ability of CD34+ HSCs.

Visible-Light-Induced Nickel-Catalyzed Cross-Coupling of Aryl Bromides with Nitriles.

Herein, a visible-light-induced nickel-catalyzed cross-coupling of aryl bromide with nitrile has been reported. By utilization of readily available nitriles as carbonyl precursors, a range of structurally diverse aryl ketones were facilely constructed. The synthetic simplicity, mild reaction conditions, and acidic functional group tolerance would broaden the synthetic utilities of this developed protocol as an expedient alternative to Grignard/organolithium protocols.

Photoredox/Nickel Dual Catalysis-Enabled Cross-Dehydrogenative C-H Amination of Indoles with Unactivated Amine.

Herein, a direct cross-dehydrogenative C-H amination of indoles has been successfully achieved, enabled by the merger of photocatalysis with nickel catalysis. This developed process does not require stoichiometric oxidants and prefunctionalization of amine partners, providing a concise platform for C-N bond formation. Moreover, the synthetic practicality of this transformation was well revealed by its high step- and atom-economy, high reaction efficiency, and broad functional group tolerance.

Nanoelectrochemistry reveals how soluble Aß42 oligomers alter vesicular storage and release of glutamate.

Glutamate (Glu) is the major excitatory transmitter in the nervous system. Impairment of its vesicular release by ß-amyloid (Aß) oligomers is thought to participate in pathological processes leading to Alzheimer's disease. However, it remains unclear whether soluble Aß42 oligomers affect intravesicular amounts of Glu or their release in the brain, or both. Measurements made in this work on single Glu varicosities with an amperometric nanowire Glu biosensor revealed that soluble Aß42 oligomers first caused a dramatic increase in vesicular Glu storage and stimulation-induced release, accompanied by a high level of parallel spontaneous exocytosis, ultimately resulting in the depletion of intravesicular Glu content and greatly reduced release. Molecular biology tools and mouse models of Aß amyloidosis have further established that the transient hyperexcitation observed during the primary pathological stage is mediated by an altered behavior of VGLUT1 responsible for transporting Glu into synaptic vesicles. Thereafter, an overexpression of Vps10p-tail-interactor-1a, a protein that maintains spontaneous release of neurotransmitters by selective interaction with t-SNAREs, resulted in a depletion of intravesicular Glu content, triggering advanced-stage neuronal malfunction. These findings are expected to open perspectives for remediating Aß42-induced neuronal hyperactivity and neuronal degeneration.

Development of a Growth-Dependent System to Regulate Cell Growth and Keratinase Production in B. subtilis.

Keratinases specifically degrade insoluble keratin waste, thus contributing to environmental protection and sustainable biomass development. However, their industrial application is hindered by inefficient enzyme production and poor biomass generation. In this study, the heterologous expression of keratinase was found to have cytotoxicity and might block host cell growth due to its proteolytic property. To address this problem, an autoregulatory expression system based on quorum sensing was developed to synergistically regulate cell growth and keratinase production in Bacillus subtilis. The growth-dependent promoter PaprE was chosen and shown to be effective in delaying keratinase production while promoting host cell proliferation. Copy number screening and core region mutations further balanced the two states. Carbon supplement optimization indicated that addition of 2% glucose facilitated biomass accumulation during the early stage of fermentation. Cell density increased to 15.6 (OD600 nm) from 8 with keratinase activity raised to 4200 U·mL-1 from 1162 U·mL-1. Keratinase was then utilized in the bioconversion of feather waste to prepare soluble keratins, polypeptides, and amino acids. This study provides a powerful system for efficient production of keratinase and paves the way for keratin waste recycling.

Precautions against COVID-19 reduce respiratory virus infections among children in Southwest China.

Acute respiratory tract infections pose a serious threat to the health of children worldwide, with viral infections representing a major etiology of this type of disease. Protective measures such as mask-wearing, social distancing, and hand hygiene can be effective in curbing the spread of severe acute respiratory syndrome coronavirus 2. These precautions may also have an impact on the spread of other respiratory viruses. In this study, we retrospectively compared the respiratory virus infections of children in Southwest China before and after the outbreak of COVID-19. Nasopharyngeal swabs were collected from 1578 patients under 14 years old with acute respiratory tract infection symptoms before and after COVID-19 pandemic. Nine common respiratory viruses including human bocavirus, human rhinoviruses, human coronaviruses, human adenoviruses, human metapneumovirus, respiratory syncytial virus, influenza A virus, influenza B virus, and parainfluenza virus were measured by advanced fragment analysis. The respiratory virus infection rates among children of all ages and genders in Southwest China under the precautions against COVID-19 pandemic were significantly lower than that of the same period before the pandemic. Our findings indicate that public health measures implemented during the COVID-19 pandemic, including strict mask-wearing, social distancing, and hand hygiene, may be effective in preventing the transmission of other respiratory viruses in children, thereby controlling the spread of infections.

A keratin/chitosan sponge with excellent hemostatic performance for uncontrolled bleeding.

Uncontrolled bleeding leads to a higher fatality rate in the situation of surgery, traffic accidents and warfare. Traditional hemostatic materials such as bandages are not ideal for uncontrolled or incompressible bleeding. Therefore, it is of great significance to develop a new medical biomaterial with excellent rapid hemostatic effect. Keratin is a natural, biocompatible and biodegradable protein which contains amino acid sequences that induce cell adhesion. As a potential biomedical material, keratin has been developed and paid attention in tissue engineering fields such as promoting wound healing and nerve repair. Herein, a keratin/chitosan (K/C) sponge was prepared to achieve rapid hemostasis. The characterizations of K/C sponge were investigated, including SEM, TGA, liquid absorption and porosity, showing that the high porosity up to 90.12 ± 2.17 % resulted in an excellent blood absorption. The cytotoxicity test and implantation experiment proved that the K/C sponge was biocompatible and biodegradable. Moreover, the prepared K/C sponge showed better hemostatic performance than chitosan sponge (CS) and the commercially available gelatin sponge in both rat tail amputation and liver trauma bleeding models. Further experiments showed that K/C sponge plays a hemostatic role through the endogenous coagulation pathway, thus shortening the activated partial thromboplastin time (APTT) effectively. Therefore, this study provided a K/C sponge which can be served as a promising biomedical hemostatic material.

Preparation and Characterization of PEDOT:PSS/TiO2 Micro/Nanofiber-Based Gas Sensors.

In this study, we employed electrospinning technology and in situ polymerization to prepare wearable and highly sensitive PVP/PEDOT:PSS/TiO2 micro/nanofiber gas sensors. PEDOT, PEDOT:PSS, and TiO2 were prepared via in situ polymerization and tested for characteristic peaks using energy-dispersive X-ray spectroscopy (EDS) and Fourier transform infrared spectroscopy (FT-IR), then characterized using a scanning electron microscope (SEM), a four-point probe resistance measurement, and a gas sensor test system. The gas sensitivity was 3.46-12.06% when ethanol with a concentration between 12.5 ppm and 6250 ppm was measured; 625 ppm of ethanol was used in the gas sensitivity measurements for the PEDOT/composite conductive woven fabrics, PVP/PEDOT:PSS nanofiber membranes, and PVP/PEDOT:PSS/TiO2 micro/nanofiber gas sensors. The latter exhibited the highest gas sensitivity, which was 5.52% and 2.35% greater than that of the PEDOT/composite conductive woven fabrics and PVP/PEDOT:PSS nanofiber membranes, respectively. In addition, the influence of relative humidity on the performance of the PVP/PEDOT:PSS/TiO2 micro/nanofiber gas sensors was examined. The electrical sensitivity decreased with a decrease in ethanol concentration. The gas sensitivity exhibited a linear relationship with relative humidity lower than 75%; however, when the relative humidity was higher than 75%, the gas sensitivity showed a highly non-linear correlation. The test results indicated that the PVP/PEDOT:PSS/TiO2 micro/nanofiber gas sensors were flexible and highly sensitive to gas, qualifying them for use as a wearable gas sensor platform at room temperature. The proposed gas sensors demonstrated vital functions and an innovative design for the development of a smart wearable device.

Alum Adjuvant and Built-in TLR7 Agonist Synergistically Enhance Anti-MUC1 Immune Responses for Cancer Vaccine.

The tumor-associated antigen mucin 1 (MUC1) is an attractive target of antitumor vaccine, but its weak immunogenicity is a big challenge for the development of vaccine. In order to enhance immune responses against MUC1, herein, we conjugated small molecular toll-like receptor 7 agonist (TLR7a) to carrier protein BSA via MUC1 glycopeptide to form a three-component conjugate (BSA-MUC1-TLR7a). Furthermore, we combined the three-component conjugate with Alum adjuvant to explore their synergistic effects. The immunological studies indicated that Alum adjuvant and built-in TLR7a synergistically enhanced anti-MUC1 antibody responses and showed Th1-biased immune responses. Meanwhile, antibodies elicited by the vaccine candidate effectively recognized tumor cells and induced complement-dependent cytotoxicity. In addition, Alum adjuvant and built-in TLR7a synergistically enhanced MUC1 glycopeptide-specific memory CD8+ T-cell immune responses. More importantly, the vaccine with the binary adjuvant can significantly inhibit tumor growth and prolong the survival time of mice in the tumor challenge experiment. This novel vaccine construct provides an effective strategy to develop antitumor vaccines.

Anti-inflammatory action of geniposide promotes wound healing in diabetic rats.

CONTEXT: As a major active iridoid glycoside from Gardenia jasminoides J. Ellis (Rubiaceae), geniposide possesses various pharmacological activities, including anti-platelet aggregation and anti-inflammatory action. OBJECTIVES: This study explores the effect of geniposide in diabetic wound model by anti-inflammatory action. MATERIALS AND METHODS: Diabetic rodent model in Wistar rats was induced by streptozotocin combined with high-fat feed. The selected rats were divided into control group, the diabetic model group and geniposide subgroups (200, 400 and 500 mg/kg), and orally administrated once daily with saline or geniposide. Wound area and histochemical indicators were measured on day 7 after continuous administration, to assess lesion retraction, inflammatory cells and fibroblasts. RESULTS: Geniposide notably enhanced lesion retraction by 1.06-1.84 times on day 7 after surgical onset in diabetic rats (p < 0.05). In the pathological experiment by HE staining, geniposide significantly reduced inflammatory cell infiltration and proliferation of fibroblasts in the central lesion regions. In diabetic rats treated with geniposide, the levels of pro-inflammatory factors (tumour necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß)) and IL-6 were significantly reduced (p < 0.05), followed with the increment of IL-10 in a dose-dependent manner. The IC50 of geniposide on TNF-α, IL-1ß and IL-6 could be calculated as 1.36, 1.02 and 1.23 g/kg, respectively. It assumed that geniposide-induced IL-10 expression contributed to inhibiting the expression of pro-inflammatory factors. DISCUSSION AND CONCLUSIONS: Geniposide promoted diabetic wound healing by anti-inflammation and adjusting blood glucose. Further topical studies are required to evaluate effects on antibacterial activity and skin regeneration.

LncRNA RUNX1-IT1 affects the differentiation of Th1 cells by regulating NrCAM transcription in Graves' disease.

Graves' disease (GD) is a kind of autoimmune diseases. The development of GD is closely related to the imbalance of Th1/Th2 generated by the differentiation of CD4+ T cells. This study was sought to clarify the role of lncRNA RUNX1-IT1 and explore the mechanism of its function. The expressions of RUNX1-IT1 and Neural cell adhesion molecule (NrCAM) in the peripheral blood of GD patients were detected by qRT-PCR and Western blot. We performed RNA pull down, RIP, and ChIP experiments to verify the correlation between p53 and RUNX1-IT1, p53 and NrCAM. The levels of Th1 cells differentiation markers were detected by Flow cytometry assay and ELISA. The expressions of lncRNA RUNX1-IT1 and NrCAM were most significantly up-regulated in CD4+ T cells of GD patients, and NrCAM expression was significantly positively correlated with RUNX1-IT1 expression. Furthermore, p53 was a potential transcription factor of NrCAM, which could interact with NrCAM. NrCAM level was up-regulated after the overexpression of p53 in CD4+ T cells, while knockdown of RUNX1-IT1 reversed this effect. Down-regulation of NrCAM and RUNX1-IT1 could decrease the mRNA and protein levels of transcriptional regulator T-bet and CXC chemokine ligand 10 (CXCL10) in CD4+ T cells. Our results suggested that RUNX1-IT1 regulated the expressions of the important Th1 factor T-bet, CXCL10, and interferon γ (IFN-γ) by regulating NrCAM transcription, thus participating in the occurrence and development of specific autoimmune disease GD.

Versatile Construction of Biomimetic Nanosensors for Electrochemical Monitoring of Intracellular Glutathione.

The current strategies for nanoelectrode functionalization usually involve sophisticated modification procedures, uncontrollable and unstable modifier assembly, as well as a limited variety of modifiers. To address this issue, we propose a versatile strategy for large-scale synthesis of biomimetic molecular catalysts (BMCs) modified nanowires (NWs) to construct functionalized electrochemical nanosensors. This design protocol employs an easy, controllable and stable assembly of diverse BMCs-poly(3,4-ethylenedioxythiophene) (PEDOT) composites on conductive NWs. The intrinsic catalytic activity of BMCs combined with outstanding electron transfer ability of conductive polymer enables the nanosensors to sensitively and selectively detect various biomolecules. Further application of sulfonated cobalt phthalocyanine functionalized nanosensors achieves real-time electrochemical monitoring of intracellular glutathione levels and its redox homeostasis in single living cells for the first time.

RBD conjugate vaccine with a built-in TLR1/2 agonist is highly immunogenic against SARS-CoV-2 and variants of concern.

The coronavirus 2019 (COVID-19) pandemic is causing serious impacts in the world, and safe and effective vaccines and medicines are the best methods to combat the disease. The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein plays a key role in interacting with the angiotensin-converting enzyme 2 (ACE2) receptor, and is regarded as an important target of vaccines. Herein, we constructed the adjuvant-protein conjugate Pam3CSK4-RBD as a vaccine candidate, in which the N-terminal of the RBD was site-selectively oxidized by transamination and conjugated with the TLR1/2 agonist Pam3CSK4. This demonstrated that the conjugation of Pam3CSK4 significantly enhanced the anti-RBD antibody response and cellular response. In addition, sera from the Pam3CSK4-RBD immunized group efficiently inhibited the binding of the RBD to ACE2 and protected cells from SARS-CoV-2 and four variants of concern (alpha, beta, gamma and delta), indicating that this adjuvant strategy could be one of the effective means for protein vaccine development.

Influence of GAS5/MicroRNA-223-3p/P2Y12 Axis on Clopidogrel Response in Coronary Artery Disease.

Background Dual antiplatelet therapy based on aspirin and P2Y12 receptor antagonists such as clopidogrel is currently the primary treatment for coronary artery disease (CAD). However, a percentage of patients exhibit clopidogrel resistance, in which genetic factors play vital roles. This study aimed to investigate the roles of GAS5 (growth arrest-specific 5) and its rs55829688 polymorphism in clopidogrel response in patients with CAD. Methods and Results A total of 444 patients with CAD receiving dual antiplatelet therapy from 2017 to 2018 were enrolled to evaluate the effect of GAS5 single nucleotide polymorphism rs55829688 on platelet reactivity index. Platelets from 37 patients of these patients were purified with microbeads to detect GAS5 and microRNA-223-3p (miR-223-3p) expression. Platelet-rich plasma was isolated from another 17 healthy volunteers and 46 newly diagnosed patients with CAD to detect GAS5 and miR-223-3p expression. A dual-luciferase reporter assay was performed to explore the interaction between miR-223-3p and GAS5 or P2Y12 3'-UTR in (human embryonic kidney 293 cell line that expresses a mutant version of the SV40 large T antigen) HEK 293T and (megakaryoblastic cell line derived in 1983 from the bone marrow of a chronic myeloid leukemia patient with megakaryoblastic crisis) MEG-01 cells. Loss-of-function and gain-of-function experiments were performed to reveal the regulation of GAS5 toward P2Y12 via miR-223-3p in MEG-01 cells. We observed that rs55829688 CC homozygotes showed significantly decreased platelet reactivity index than TT homozygotes in CYP2C19 poor metabolizers. Platelet GAS5 expression correlated positively with both platelet reactivity index and P2Y12 mRNA expressions, whereas platelet miR-223-3p expression negatively correlated with platelet reactivity index. Meanwhile, a negative correlation between GAS5 and miR-223-3p expressions was observed in platelets. MiR-223-3p mimic reduced while the miR-223-3p inhibitor increased the expression of GAS5 and P2Y12 in MEG-01 cells. Knockdown of GAS5 by siRNA increased miR-223-3p expression and decreased P2Y12 expression, which could be reversed by the miR-223-3p inhibitor. Meanwhile, overexpression of GAS5 reduced miR-223-3p expression and increased P2Y12 expression, which could be reversed by miR-223-3p mimic. Conclusions GAS5 rs55829688 polymorphism might affect clopidogrel response in patients with CAD with the CYP2C19 poor metabolizer genotypes, and GAS5 regulates P2Y12 expression and clopidogrel response by acting as a competitive endogenous RNA for miR-223-3p.

Large-Scale Synthesis of Functionalized Nanowires to Construct Nanoelectrodes for Intracellular Sensing.

A strategy for one-pot and large-scale synthesis of functionalized core-shell nanowires (NWs) to high-efficiently construct single nanowire electrodes is proposed. Based on the polymerization reaction between 3,4-ethylenedioxythiophene (EDOT) and noble metal cations, manifold noble metal nanoparticles-polyEDOT (PEDOT) nanocomposites can be uniformly modified on the surface of any nonconductive NWs. This provides a facile and versatile approach to produce massive number of core-shell NWs with excellent conductivity, adjustable size, and well-designed properties. Nanoelectrodes manufactured with such core-shell NWs exhibit excellent electrochemical performance and mechanical stability as well as favorable antifouling properties, which are demonstrated by in situ intracellular monitoring of biological molecules (nitric oxide) and unraveling its relevant unclear signaling pathway inside single living cells.