Therapeutic Inhibition of LincRNA-p21 Protects Against Cardiac Hypertrophy.

BACKGROUND: Cardiac hypertrophy is an adaptive response to pressure overload aimed at maintaining cardiac function. However, prolonged hypertrophy significantly increases the risk of maladaptive cardiac remodeling and heart failure. Recent studies have implicated long noncoding RNAs in cardiac hypertrophy and cardiomyopathy, but their significance and mechanism(s) of action are not well understood. METHODS: We measured lincRNA-p21 RNA and H3K27ac levels in the hearts of dilated cardiomyopathy patients. We assessed the functional role of lincRNA-p21 in basal and surgical pressure-overload conditions using loss-of-function mice. Genome-wide transcriptome analysis revealed dysregulated genes and pathways. We labeled proteins in proximity to full-length lincRNA-p21 using a novel BioID2-based system. We immunoprecipitated lincRNA-p21-interacting proteins and performed cell fractionation, ChIP-seq (chromatin immunoprecipitation followed by sequencing), and co-immunoprecipitation to investigate molecular interactions and underlying mechanisms. We used GapmeR antisense oligonucleotides to evaluate the therapeutic potential of lincRNA-p21 inhibition in cardiac hypertrophy and associated heart failure. RESULTS: lincRNA-p21 was induced in mice and humans with cardiomyopathy. Global and cardiac-specific lincRNA-p21 knockout significantly suppressed pressure overload-induced ventricular wall thickening, stress marker elevation, and deterioration of cardiac function. Genome-wide transcriptome analysis and transcriptional network analysis revealed that lincRNA-p21 acts in trans to stimulate the NFAT/MEF2 (nuclear factor of activated T cells/myocyte enhancer factor-2) pathway. Mechanistically, lincRNA-p21 is bound to the scaffold protein KAP1 (KRAB-associated protein-1). lincRNA-p21 cardiac-specific knockout suppressed stress-induced nuclear accumulation of KAP1, and KAP1 knockdown attenuated cardiac hypertrophy and NFAT activation. KAP1 positively regulates pathological hypertrophy by physically interacting with NFATC4 to promote the overactive status of NFAT/MEF2 signaling. GapmeR antisense oligonucleotide depletion of lincRNA-p21 similarly inhibited cardiac hypertrophy and adverse remodeling, highlighting the therapeutic potential of inhibiting lincRNA-p21. CONCLUSIONS: These findings advance our understanding of the functional significance of stress-induced long noncoding RNA in cardiac hypertrophy and demonstrate the potential of lincRNA-p21 as a novel therapeutic target for cardiac hypertrophy and subsequent heart failure.

Molecular Connectors Boosting the Performance of MoS2 Cathodes in Zinc-Ion Batteries.

Zinc-ion batteries (ZIBs) are promising energy storage systems due to high energy density, low-cost, and abundant availability of zinc as a raw material. However, the greatest challenge in ZIBs research is lack of suitable cathode materials that can reversibly intercalate Zn2+ ions. 2D layered materials, especially MoS2-based, attract tremendous interest due to large surface area and ability to intercalate/deintercalate ions. Unfortunately, pristine MoS2 obtained by traditional protocols such as chemical exfoliation or hydrothermal/solvothermal methods exhibits limited electronic conductivity and poor chemical stability upon charge/discharge cycling. Here, a novel molecular strategy to boost the electrochemical performance of MoS2 cathode materials for aqueous ZIBs is reported. The use of dithiolated conjugated molecular pillars, that is, 4,4'-biphenyldithiols, enables to heal defects and crosslink the MoS2 nanosheets, yielding covalently bridged networks (MoS2-SH2) with improved ionic and electronic conductivity and electrochemical performance. In particular, MoS2-SH2 electrodes display high specific capacity of 271.3 mAh g-1 at 0.1 A g-1, high energy density of 279 Wh kg-1, and high power density of 12.3 kW kg-1. With its outstanding rate capability (capacity of 148.1 mAh g-1 at 10 A g-1) and stability (capacity of 179 mAh g-1 after 1000 cycles), MoS2-SH2 electrodes outperform other MoS2-based electrodes in ZIBs.

Population pharmacokinetics of daptomycin in critically ill patients receiving extracorporeal membrane oxygenation.

BACKGROUND: Daptomycin is widely used in critically ill patients for Gram-positive bacterial infections. Extracorporeal membrane oxygenation (ECMO) is increasingly used in this population and can potentially alter the pharmacokinetic (PK) behaviour of antibiotics. However, the effect of ECMO has not been evaluated in daptomycin. Our study aims to explore the effect of ECMO on daptomycin in critically ill patients through population pharmacokinetic (PopPK) analysis and to determine optimal dosage regimens based on both efficacy and safety considerations. METHODS: A prospective, open-label PK study was carried out in critically ill patients with or without ECMO. The total concentration of daptomycin was determined by UPLC-MS/MS. NONMEM was used for PopPK analysis and Monte Carlo simulations. RESULTS: Two hundred and ninety-three plasma samples were collected from 36 critically ill patients, 24 of whom received ECMO support. A two-compartment model with first-order elimination can best describe the PK of daptomycin. Creatinine clearance (CLCR) significantly affects the clearance of daptomycin while ECMO has no significant effect on the PK parameters. Monte Carlo simulations showed that, when the MICs for bacteria are  ≥1 mg/L, the currently recommended dosage regimen is insufficient for critically ill patients with CLCR > 30 mL/min. Our simulations suggest 10 mg/kg for patients with CLCR between 30 and 90 mL/min, and 12 mg/kg for patients with CLCR higher than 90 mL/min. CONCLUSIONS: This is the first PopPK model of daptomycin in ECMO patients. Optimal dosage regimens considering efficacy, safety, and pathogens were provided for critical patients based on pharmacokinetic-pharmacodynamic analysis.

First principles study of a triazine-based covalent organic framework as a high-capacity anode material for Na/K-ion batteries.

The rational design of high-performance anode materials is crucial for the development of rechargeable Na-ion batteries (NIBs) and K-ion batteries (KIBs). In this study, based on density functional theory (DFT) calculations, we have systematically investigated the possibility of a bilayer triazine-based covalent organic framework (bilayer TCOF) as an anode for NIBs and KIBs. The calculation of the electronic band structure shows that the bilayer TCOF is a direct band gap semiconductor with a band gap of 2.01 eV. After the adsorption of Na/K at the most favorable sites, the bilayer TCOF transitions from a semiconductor to a metal state, guaranteeing good electronic conductivity. The low diffusion barriers of the bilayer TCOF are 0.45 and 0.26 eV, respectively, indicating a fast diffusion rate of Na/K ions. In addition, the bilayer TCOF has a theoretical storage capacity of up to 628 mA h g-1. Finally, it is found that the average voltage of the bilayer TCOF for NIBs and KIBs is 0.53 and 0.48 V, respectively. Based on these results, we can conclude that the bilayer TCOF may be a suitable anode material for NIBs and KIBs.

A Nomogram Based on Nutrition-Related Indicators and Computed Tomography Imaging Features for Predicting Preoperative Lymph Node Metastasis in Curatively Resected Esophagogastric Junction Adenocarcinoma.

BACKGROUNDS: Preoperative noninvasive tools to predict pretreatment lymph node metastasis (PLNM) status accurately for esophagogastric junction adenocarcinoma (EJA) are few. Thus, the authors aimed to construct a nomogram for predicting PLNM in curatively resected EJA. METHODS: This study enrolled 638 EJA patients who received curative surgery resection and divided them randomly (7:3) into training and validation groups. For nomogram construction, 26 candidate parameters involving 21 preoperative clinical laboratory blood nutrition-related indicators, computed tomography (CT)-reported tumor size, CT-reported PLNM, gender, age, and body mass index were screened. RESULTS: In the training group, Lasso regression included nine nutrition-related blood indicators in the PLNM-prediction nomogram. The PLNM prediction nomogram yielded an area under the receiver operating characteristic (ROC) curve of 0.741 (95 % confidence interval [CI], 0.697-0.781), which was better than that of the CT-reported PLNM (0.635; 95% CI 0.588-0.680; p < 0.0001). Application of the nomogram in the validation cohort still gave good discrimination (0.725 [95% CI 0.658-0.785] vs 0.634 [95% CI 0.563-0.700]; p = 0.0042). Good calibration and a net benefit were observed in both groups. CONCLUSIONS: This study presented a nomogram incorporating preoperative nutrition-related blood indicators and CT imaging features that might be used as a convenient tool to facilitate the preoperative individualized prediction of PLNM for patients with curatively resected EJA.

Cardiac CIP protein regulates dystrophic cardiomyopathy.

Heart failure is a leading cause of fatality in Duchenne muscular dystrophy (DMD) patients. Previously, we discovered that cardiac and skeletal-muscle-enriched CIP proteins play important roles in cardiac function. Here, we report that CIP, a striated muscle-specific protein, participates in the regulation of dystrophic cardiomyopathy. Using a mouse model of human DMD, we found that deletion of CIP leads to dilated cardiomyopathy and heart failure in young, non-syndromic mdx mice. Conversely, transgenic overexpression of CIP reduces pathological dystrophic cardiomyopathy in old, syndromic mdx mice. Genome-wide transcriptome analyses reveal that molecular pathways involving fibrogenesis and oxidative stress are affected in CIP-mediated dystrophic cardiomyopathy. Mechanistically, we found that CIP interacts with dystrophin and calcineurin (CnA) to suppress the CnA-Nuclear Factor of Activated T cells (NFAT) pathway, which results in decreased expression of Nox4, a key component of the oxidative stress pathway. Overexpression of Nox4 accelerates the development of dystrophic cardiomyopathy in mdx mice. Our study indicates CIP is a modifier of dystrophic cardiomyopathy and a potential therapeutic target for this devastating disease.

Rapidly progressive interstitial lung disease combined with pneumocystis jiroveci pneumonia in a patient with single anti-TIF-1γ antibody positive dermatomyositis in the context of an underlying tumor.

BACKGROUND: Interstitial lung disease (ILD) is a frequently observed comorbidity in autoimmune diseases such as dermatomyositis/polymyositis (DM/PM), and it is significantly associated with specific autoantibody types. One unique antibody type is the anti-transcription intermediate factor-1γ antibody (anti-TIF-1γ Ab), which has a positive rate of only 7%. It is often found in combination with malignancy and rarely with ILD, particularly rapidly progressive ILD (RPILD). In some cases, the presence of ILD in individuals with DM may indicate a paraneoplastic syndrome. Pneumocystis jiroveci pneumonia (PJP) typically occurs due to intensive immunosuppressive therapy, human immunodeficiency virus (HIV) infection, or malignancy, and rarely as an isolated condition. CASE PRESENTATION: A 52-year-old man with a history of rapid weight loss but non-HIV infected and not immunosuppressed who presented with fever, cough, dyspnea, weakness of the extremities, characteristic rash and mechanic's hand. Pathogenic tests suggested PJP, laboratory tests suggested a single anti-TIF-1γ Ab positive DM, imaging suggested ILD, and pathology revealed no malignancy. RPILD and acute respiratory distress syndrome (ARDS) developed after anti-infection and steroid hormone therapy. After mechanical support therapy such as Extracorporeal Membrane Oxygenation (ECMO), the patient developed late-onset cytomegalovirus pneumonia (CMVP), complicated bacterial infection, and ultimately death. Additionally, we discuss the potential causes of rapid weight loss, the mechanisms by which anti-TIF-1γ Ab may lead to ILD, and the possible connection between anti-TIF-1γ Ab positivity, rapid weight loss, immune abnormalities, and opportunistic infections. CONCLUSIONS: This case emphasizes the importance of early recognition of malignant tumors and pulmonary lesions, assessment of the body's immune status, prompt initiation of immunosuppressive treatment, and prevention of opportunistic infections in individuals with single anti-TIF-1γ Ab positive DM presenting with rapid weight loss.

[Neuroprotective effect and mechanism of Zuogui Jiangtang Jieyu Formula on diabetes mellitus complicated with depression model rats based on CX3CL1-CX3CR1 axis].

Based on the CX3C chemokine ligand 1(CX3CL1)-CX3C chemokine receptor 1(CX3CR1) axis, this study explored the potential mechanism by which Zuogui Jiangtang Jieyu Formula(ZGJTJY) improved neuroinflammation and enhanced neuroprotective effect in a rat model of diabetes mellitus complicated with depression(DD). The DD rat model was established by feeding a high-fat diet combined with streptozotocin(STZ) intraperitoneal injection for four weeks and chronic unpredictable mild stress(CUMS) combined with isolated cage rearing for five weeks. The rats were divided into a control group, a model group, a positive control group, an inhibitor group, and a ZGJTJY group. The open field test and forced swimming test were used to assess the depression-like behaviors of the rats. Enzyme-linked immunosorbent assay(ELISA) was performed to measure the expression levels of the pro-inflammatory cytokines interleukin-1ß(IL-1ß) and tumor necrosis factor-α(TNF-α) in plasma. Immunofluorescence staining was used to detect the expression of ionized calcium-binding adapter molecule 1(Iba1), postsynaptic density protein-95(PSD95), and synapsin-1(SYN1) in the hippocampus. Hematoxylin-eosin(HE) staining, Nissl staining, and TdT-mediated dUTP nick end labeling(TUNEL) fluorescence staining were performed to assess hippocampal neuronal damage. Western blot was used to measure the expression levels of CX3CL1, CX3CR1, A2A adenosine receptor(A2AR), glutamate receptor 2A(NR2A), glutamate receptor 2B(NR2B), and brain-derived neurotrophic factor(BDNF) in the hippocampus. Compared with the model group, the ZGJTJY group showed improved depression-like behaviors in DD rats, enhanced neuroprotective effect, increased expression of PSD95, SYN1, and BDNF(P<0.01), and decreased expression of Iba1, IL-1ß, and TNF-α(P<0.01), as well as the expression of CX3CL1, CX3CR1, A2AR, NR2A, and NR2B(P<0.01). These results suggest that ZGJTJY may exert its neuroprotective effect by inhibiting the CX3CL1-CX3CR1 axis and activation of hippocampal microglia, thereby improving neuroinflammation and abnormal activation of N-methyl-D-aspartate receptor(NMDAR) subunits, and ultimately enhancing the expression of synaptic-related proteins PSD95, SYN1, and BDNF in the hippocampus.

Supramolecular Engineering of Cathode Materials for Aqueous Zinc-ion Energy Storage Devices: Novel Benzothiadiazole Functionalized Two-Dimensional Olefin-Linked COFs.

Two-dimensional covalent organic frameworks (COFs) have emerged as promising materials for energy storage applications exhibiting enhanced electrochemical performance. While most of the reported organic cathode materials for zinc-ion batteries use carbonyl groups as electrochemically-active sites, their high hydrophilicity in aqueous electrolytes represents a critical drawback. Herein, we report a novel and structurally robust olefin-linked COF-TMT-BT synthesized via the aldol condensation between 2,4,6-trimethyl-1,3,5-triazine (TMT) and 4,4'-(benzothiadiazole-4,7-diyl)dibenzaldehyde (BT), where benzothiadiazole units are explored as novel electrochemically-active groups. Our COF-TMT-BT exhibits an outstanding Zn2+ storage capability, delivering a state-of-the-art capacity of 283.5 mAh g-1 at 0.1 A g-1 . Computational and experimental analyses reveal that the charge-storage mechanism in COF-TMT-BT electrodes is based on the supramolecularly engineered and reversible Zn2+ coordination by the benzothiadiazole units.

AMCC nonlinear baseband superimposition and extraction aided by proposed interference cancellation for WDM-PON used in 5G mobile fronthaul.

As the demand for mobile Internet capacity explodes, the research on fifth-generation (5G) mobile communication systems has gradually deepened, which has stringent requirements for latency and transmission capacity, especially in the section called mobile fronthaul (MFH). Wavelength division multiplexing passive optical network (WDM-PON) is an attractive technology for 5G MFH which requires an auxiliary management and control channel (AMCC) to achieve efficient network deployment. In previous studies, more research has been done on AMCC superimposition methods and transmission performance on 10 Gbps WDN-PON systems, and the role of AMCC in wavelength management has been studied at the system level. In this paper, we realize non-linear baseband modulation of AMCC signals up to 20 Mbps in a single wavelength 25-Gbps PON system through the distributed feed-back laser and Mach-Zehnder modulator. At the receiving end, we propose a low-complexity interference cancellation method to suppress the interference caused by WDM-PON signals and significantly reduce the bit error rate of AMCC signals. The method realizes a simplified scheme to reconstruct the PON signals by analyzing the characteristics of nonlinear modulation and the reconstructed signals can be applied to the original AMCC signals through filtering and subtraction to eliminate interference. These operations have low complexity and can be easily implemented by analog circuits, thus making it an effective way to improve the quality of AMCC signals. With the help of the proposed method, AMCC transmission at 20 Mbps can be achieved with different modulation depths, which is very promising for 5G MFH.

Dual effect of ultraviolet B on cholesterol efflux and regulated by ultraviolet radiation resistance-associated gene-mediated autophagy.

OBJECTIVE: In addition to diet and metabolism, the occurrence of foam cells and atherosclerosis are also related to environmental factors. Individual studies have shown that ultraviolet B (UVB) can regulate the progression of atherosclerosis, but with different results. Whether or not UVB has a dual effect on atherosclerosis and what mechanism is involved has not been reported. METHODS: After THP-1-derived foam cells were treated with UVB in different ways, the effects of UVB on foam cells were investigated by western blotting, cholesterol efflux experiment, oil red O staining and other methods. RESULTS: UVB plays a dual role on foam cell formation, and this effect is related to cholesterol efflux. UVB of 50 mJ/cm2 can promote cholesterol efflux in foam cells, while UVB of 200 mJ/cm2 can inhibit cholesterol efflux. UVB induces cholesterol efflux from foam cells in an autophagy-dependent manner, as the beneficial effect of UVB at 50 mJ/cm2 can be reversed by the autophagy inhibitor 3-Methyladenine (3-MA). In addition, silencing the expression of ultraviolet radiation resistance-associated gene (UVRAG) can inhibit autophagy and reduce cholesterol efflux, and overexpressing UVRAG yields the opposite result. CONCLUSION: In conclusion, our research proves that UVB exhibits a dual role in foam cell formation by regulating cholesterol efflux. Further more, we also reveal that UVRAG-mediated autophagy is the underlying mechanism of UVB-induced cholesterol efflux.

Critical Advances in Ambient Air Operation of Nonaqueous Rechargeable Li-Air Batteries.

Over the past few years, great attention has been given to nonaqueous lithium-air batteries owing to their ultrahigh theoretical energy density when compared with other energy storage systems. Most of the research interest, however, is dedicated to batteries operating in pure or dry oxygen atmospheres, while Li-air batteries that operate in ambient air still face big challenges. The biggest challenges are H2 O and CO2 that exist in ambient air, which can not only form byproducts with discharge products (Li2 O2 ), but also react with the electrolyte and the Li anode. To this end, recent progress in understanding the chemical and electrochemical reactions of Li-air batteries in ambient air is critical for the development and application of true Li-air batteries. Oxygen-selective membranes, multifunctional catalysts, and electrolyte alternatives for ambient air operational Li-air batteries are presented and discussed comprehensively. In addition, separator modification and Li anode protection are covered. Furthermore, the challenges and directions for the future development of Li-air batteries are presented.

Nomogram based on clinical characteristics and serological inflammation markers to predict overall survival of oral tongue squamous cell carcinoma patient after surgery.

BACKGROUND: Oral tongue squamous cell carcinoma (OTSCC) is a prevalent malignant disease that is characterized by high rates of metastasis and postoperative recurrence. The aim of this study was to establish a nomogram to predict the outcome of OTSCC patients after surgery. METHODS: We retrospectively analyzed 169 OTSCC patients who underwent treatments in the Cancer Hospital of Shantou University Medical College from 2008 to 2019. The Cox regression analysis was performed to determine the independent prognostic factors associated with patient's overall survival (OS). A nomogram based on these prognostic factors was established and internally validated using a bootstrap resampling method. RESULTS: Multivariate Cox regression analysis revealed the independent prognostic factors for OS were TNM stage, age, lymphocyte-to-monocyte ratio and immunoglobulin G, all of which were identified to create the nomogram. The Akaike Information Criterion and Bayesian Information Criterion of the nomogram were lower than those of TNM stage (292.222 vs. 305.480; 298.444 vs. 307.036, respectively), indicating a better goodness-of-fit of the nomogram for predicting OS. The bootstrap-corrected of concordance index (C-index) of nomogram was 0.784 (95% CI 0.708-0.860), which was higher than that of TNM stage (0.685, 95% CI 0.603-0.767, P = 0.017). The results of time-dependent C-index for OS also showed that the nomogram had a better discriminative ability than that of TNM stage. The calibration curves of the nomogram showed good consistency between the probabilities and observed values. The decision curve analysis also revealed the potential clinical usefulness of the nomogram. Based on the cutoff value obtained from the nomogram, the proposed high-risk group had poorer OS than low-risk group (P < 0.0001). CONCLUSIONS: The nomogram based on clinical characteristics and serological inflammation markers might be useful for outcome prediction of OTSCC patient.

The Physical and Psychological Effects of Personal Protective Equipment on Health Care Workers in Wuhan, China: A Cross-Sectional Survey Study.

INTRODUCTION: The purpose of this study was to rapidly quantify the safety measures regarding donning and doffing personal protective equipment, complaints of discomfort caused by wearing personal protective equipment, and the psychological perceptions of health care workers in hospitals in Wuhan, China, responding to the outbreak. METHODS: A cross-sectional online questionnaire design was used Data were collected from March 14, 2020, to March 16, 2020, in Wuhan, China. Descriptive statistics and χ2 analyses testing were used. RESULTS: Standard nosocomial infection training could significantly decrease the occurrence of infection (3.6% vs 13.0%, χ2 = 4.47, P < 0.05). Discomfort can be classified into 7 categories. Female sex (66.0% vs 50.5%, χ2 = 6.37), occupation (62.7% vs 30.8%, χ2 = 5.33), working at designated hospitals (44.8% vs 26.7%, χ2 = 5.17) or in intensive care units (70.4% vs 57.9%, χ2 = 3.88), and working in personal protective equipment for > 4 hours (62.2% vs 39.2%, χ2 = 9.17) led to more complaints about physical discomfort or increased occurrence of pressure sores (all P < 0.05). Psychologically, health care workers at designated hospitals (60.0% vs 42.1%, χ2 = 4.97) or intensive care units (55.9% vs 41.5%, χ2 = 4.40) (all P < 0.05) expressed different rates of pride. DISCUSSION: Active training on infection and protective equipment could reduce the infection risk. Working for long hours increased the occurrence of discomfort and skin erosion. Reducing the working hours and having adequate protective products and proper psychological interventions may be beneficial to relieve discomfort.

Vacancy Engineering of Iron-Doped W18 O49 Nanoreactors for Low-Barrier Electrochemical Nitrogen Reduction.

The electrochemical nitrogen reduction reaction (NRR) is a promising energy-efficient and low-emission alternative to the traditional Haber-Bosch process. Usually, the competing hydrogen evolution reaction (HER) and the reaction barrier of ambient electrochemical NRR are significant challenges, making a simultaneous high NH3 formation rate and high Faradic efficiency (FE) difficult. To give effective NRR electrocatalysis and suppressed HER, the surface atomic structure of W18 O49 , which has exposed active W sites and weak binding for H2 , is doped with Fe. A high NH3 formation rate of 24.7 µg h-1 mgcat -1 and a high FE of 20.0 % are achieved at an overpotential of only -0.15 V versus the reversible hydrogen electrode. Ab initio calculations reveal an intercalation-type doping of Fe atoms in the tunnels of the W18 O49 crystal structure, which increases the oxygen vacancies and exposes more W active sites, optimizes the nitrogen adsorption energy, and facilitates the electrocatalytic NRR.

Prognostic value of repeated serum kisspeptin measurements in early first trimester pregnancy: a preliminary study.

RESEARCH QUESTION: What is the diagnostic value of maternal kisspeptin in patients with asymptomatic first-trimester pregnancies, and what is the prognostic significance of kisspeptin versus beta-HCG in early pregnancies. DESIGN: Case-control study in academic medical centres. Patients with no confounding co-morbidities who conceived by IVF and intracytoplasmic sperm injection were analysed. Maternal serum samples were assessed at the time of pregnancy testing. Women who achieved a positive pregnancy test were asked to take serum samples 4 days later. According to the follow-up results, patients who experienced biochemical pregnancy loss (n = 24) and early miscarriage (n = 21), and women who achieved a viable pregnancy (n = 28), were included in this study. Serum samples were collected to detect kisspeptin and beta-HCG, respectively. RESULTS: Single serum determinations of kisspeptin and beta-HCG were correlated with the different pregnancy outcomes. Women who experienced biochemical pregnancy loss showed lower kisspeptin levels than those in groups B and C. No significant difference, however, was observed at the time of pregnancy testing in women who had experienced early miscarriage and those who had achieved viable pregnancy. Sequential measurements of serum kisspeptin are not as effective as beta-HCG in determining pregnancy outcome. Increased kisspeptin level was associated with reduced miscarriage risk. CONCLUSION: Single serum measurement of kisspeptin is significantly altered in pregnant and non-pregnant women. However, it failed to discriminate between miscarriage and ongoing pregnancies in first-trimester pregnancy. Neither single nor sequential kisspeptin have higher diagnostic performance for miscarriage than beta-HCG in early stage.

Combined detection of serum autoantibodies as diagnostic biomarkers in esophagogastric junction adenocarcinoma.

BACKGROUND: We previously found that autoantibodies against a panel of six tumor-associated antigens (p53, NY-ESO-1, MMP-7, Hsp70, PRDX6 and Bmi-1) may aid in early detection of esophageal squamous cell carcinoma. Here we aimed to evaluate the diagnostic value of this autoantibody panel in esophagogastric junction adenocarcinoma (EJA) patients. METHODS: Serum autoantibody levels were measured by enzyme-linked immunosorbent assay in a training cohort and a validation cohort. We used receiver-operating characteristics (ROC) to calculate diagnostic accuracy. RESULTS: We recruited 169 normal controls and 122 EJA patients to the training cohort, and 80 normal controls and 70 EJA patients to the validation cohort. Detection of the autoantibody panel demonstrated an area under the curve (AUC) of 0.818, sensitivity 59.0% and specificity 90.5% in training cohort, and AUC 0.815, sensitivity 61.4% and specificity 90.0% in validation cohort in the diagnosis of EJA. Measurement of the autoantibody panel could distinguish early stage EJA patients from normal controls (AUC 0.786 and 0.786, sensitivity 50.0% and 56.0%, and specificity 90.5% and 90.0%, for training and validation cohorts, respectively). Moreover, a restricted panel consisting of autoantibodies against p53, NY-ESO-1 and Bmi-1 exhibited similar diagnostic performance for EJA (AUC 0.814 and 0.823, sensitivity 53.5% and 60.0%, and specificity 90.5% and 93.7%, for training and validation cohorts, respectively) and early stage EJA (AUC 0.744 and 0.773, sensitivity 55.6% and 52.0%, and specificity 90.5% and 93.7%, for training and validation cohorts, respectively). CONCLUSIONS: Autoantibodies against an optimized TAA panel as serum biomarkers appear to help identify the present of early stage EJA.

Inhibition of cardiac hypertrophy by aromadendrin through down-regulating NFAT and MAPKs pathways.

Cardiac hypertrophy is a maladaptive response to pressure overload and it's an important risk factor for heart failure and other adverse cardiovascular events. Aromadendrin (ARO) has remarkable anti-lipid peroxidation efficacy and is a potential therapeutic medicine for the management of diabetes and cardiovascular diseases. In this study, we established the cardiac hypertrophy cell model in rat neonatal ventricular cardiomyocytes (RNVMs) with phenylephrine. The cell model was characterized by the increased protein synthesis and cardiomyocyte size, which can be normalized by ARO treatment in both concentration- and time-dependent manner. In transverse aortic constriction (TAC) induced cardiac hypertrophy model, ARO administration improved the impairment of cardiac function and alleviated the cardiac hypertrophy indicators, like ventricular mass/body weight, myocyte cross-sectional area, and the expression of ANP, BNP and Myh7. ARO treatment also suppressed the cardiac fibrosis and the correlated fibrogenic genes. Our further investigation revealed ARO could down-regulate pressure overload-induced Malondialdehyde (MDA) and 4-HNE expression, restore the decrease of GSH/GSSG ratio, meanwhile prevent nuclear translocation of NFAT and the activation of MAPKs pathways. Collectively, ARO has a protective effect against experimental cardiac hypertrophy in mice, suggesting its potential as a novel therapeutic drug for pathological cardiac hypertrophy.

Activating transcription factor 3 in cardiovascular diseases: a potential therapeutic target.

Cardiovascular diseases (CVDs) are the primary causes of death worldwide. Among the numerous signaling molecules involved in CVDs, transcriptional factors directly influence gene expression and play a critical role in regulating cell function and the development of diseases. Activating transcription factor (ATF) 3 is an adaptive-response gene in the ATF/cAMP responsive element-binding (CREB) protein family of transcription factors that acts as either a repressor or an activator of transcription via the formation of homodimers or heterodimers with other ATF/CREB members. A appropriate ATF3 expression is important for the normal physiology of cells, and dysfunction of ATF3 is associated with various pathophysiological responses such as inflammation, apoptosis, oxidative stress and endoplasmic reticulum stress, and diseases, including CVDs. This review focuses on the role of ATF3 in cardiac hypertrophy, heart failure, atherosclerosis, ischemic heart diseases, hypertension and diabetes mellitus to provide a novel therapeutic target for CVDs.

Over-expression of a grafting-responsive gene from hickory increases abiotic stress tolerance in Arabidopsis.

KEY MESSAGE: A grafting response gene CcPIP1;2 was cloned from hickory plant, further functional characterization of the gene for water transport activity and abiotic stress tolerances were carried out through heterologous expression in Xenopus and Arabidopsis. Plasma membrane intrinsic proteins (PIPs) are multifunctional channel proteins belonging to the membrane intrinsic protein (MIP) family. In this study, a grafting-responsive gene from hickory (CcPIP1;2) was cloned and functionally characterized. Application of non-selective water inhibitors (HgCl2 and phloretin) led to the death of grafted hickory plants at 30 days after grafting (DAG). Furthermore, the transcript accumulation of the selected CcPIP1;2 gene was gradually decreased from 0 to 14 DAG in the grafted samples under inhibitor treatment conditions. Transient expression analysis of the GFP-CcPIP1;2 fusion protein showed that CcPIP1;2 was located at plasma membrane. Heterologous expression of CcPIP1;2 protein in the Xenopus oocyte system helped the access of water into the cells. Over-expression of CcPIP1;2 in Arabidopsis improved the percentage of seed germination when the seeds were grown in H2O2-, ABA-, and mannitol-containing media, but had no effect when grown in the salt containing media. CcPIP1;2 transgenic plants grew better under drought conditions. The expression of various ABA-related stress marker genes as well as cell wall expansin marker genes was significantly higher in CcPIP1;2 over-expression Arabidopsis lines than in the wild type (WT).