Heterophase Intermetallic Compounds for Electrocatalytic Hydrogen Production at Industrial-Scale Current Densities.

Heterophase nanomaterials have sparked significant research interest in catalysis due to their distinctive properties arising from synergistic effects of different components and the formed phase boundary. However, challenges persist in the controlled synthesis of heterophase intermetallic compounds (IMCs), primarily due to the lattice mismatch of distinct crystal phases and the difficulty in achieving precise control of the phase transitions. Herein, orthorhombic/cubic Ru2Ge3/RuGe IMCs with engineered boundary architecture are synthesized and anchored on the reduced graphene oxide. The Ru2Ge3/RuGe IMCs exhibit excellent hydrogen evolution reaction (HER) performance with a high current density of 1000 mA cm-2 at a low overpotential of 135 mV. The presence of phase boundaries enhances charge transfer and improves the kinetics of water dissociation while optimizing the processes of hydrogen adsorption/desorption, thus boosting the HER performance. Moreover, an anion exchange membrane electrolyzer is constructed using Ru2Ge3/RuGe as the cathode electrocatalyst, which achieves a current density of 1000 mA cm-2 at a low voltage of 1.73 V, and the activity remains virtually undiminished over 500 h.

LIPID TRANSFER PROTEIN4 regulates cotton ceramide content and activates fiber cell elongation.

Cell elongation is a fundamental process for plant growth and development. Studies have shown lipid metabolism plays important role in cell elongation; however, the related functional mechanisms remain largely unknown. Here, we report that cotton (Gossypium hirsutum) LIPID TRANSFER PROTEIN4 (GhLTP4) promotes fiber cell elongation via elevating ceramides (Cers) content and activating auxin-responsive pathways. GhLTP4 was preferentially expressed in elongating fibers. Over-expression and down-regulation of GhLTP4 led to longer and shorter fiber cells, respectively. Cers were greatly enriched in GhLTP4-overexpressing lines and decreased dramatically in GhLTP4 down-regulating lines. Moreover, auxin content and transcript levels of indole-3-acetic acid (IAA)-responsive genes were significantly increased in GhLTP4-overexpressing cotton fibers. Exogenous application of Cers promoted fiber elongation, while NPA (N-1-naphthalic acid, a polar auxin transport inhibitor) counteracted the promoting effect, suggesting that IAA functions downstream of Cers in regulating fiber elongation. Furthermore, we identified a basic helix-loop-helix transcription factor, GhbHLH105, that binds to the E-box element in the GhLTP4 promoter region and promotes the expression of GhLTP4. Suppression of GhbHLH105 in cotton reduced the transcripts level of GhLTP4, resulting in smaller cotton bolls and decreased fiber length. These results provide insights into the complex interactions between lipids and auxin-signaling pathways to promote plant cell elongation.

Insulin resistance and coronary inflammation in patients with coronary artery disease: a cross-sectional study.

BACKGROUND: Insulin resistance (IR) is associated with coronary artery disease (CAD) severity. However, its underlying mechanisms are not fully understood. Therefore, our study aimed to explore the relationship between IR and coronary inflammation and investigate the synergistic and mediating effects of coronary inflammation on the association between IR and CAD severity. METHODS: Consecutive patients with CAD who underwent coronary angiography and coronary computed tomography angiography between April 2018 and March 2023 were enrolled. The triglyceride-glucose index (TyG index) and peri-coronary adipose tissue (PCAT) attenuation around the proximal right coronary artery (RCA) were used to evaluate IR and coronary inflammation, respectively. The correlation between the TyG index and PCAT attenuation was analyzed using linear regression models. Logistic regression models were further used for investigating the correlation of the TyG index and PCAT attenuation with CAD severity. A mediation analysis assessed the correlation between IR and CAD severity mediated by coronary inflammation. RESULTS: A total of 569 participants (mean age, 62 ± 11 years; 67.8% men) were included in the study. PCAT attenuation was positively associated with the TyG index (r = 0.166; P < 0.001). After adjusting for potential confounders, the per standard deviation increment in the TyG index was associated with a 1.791 Hounsfield unit (HU) increase (95% confidence interval [CI], 0.920-2.662 HU; P < 0.001) in the PCAT attenuation. In total, 382 (67.1%) patients had multivessel CAD. The patients in the high-TyG index/high PCAT attenuation group had approximately 3.2 times the odds of multivessel CAD compared with those in the low-TyG index/low PCAT attenuation group (odds ratio, 3.199; 95%CI, 1.826-5.607; P < 0.001). Mediation analysis indicated that PCAT attenuation mediated 31.66% of the correlation between the TyG index and multivessel CAD. CONCLUSIONS: The TyG index positively correlated with PCAT attenuation in patients with CAD. The TyG index and PCAT attenuation showed a synergistic correlation with multivessel CAD. Furthermore, PCAT attenuation partially mediated the relationship between the TyG index and CAD severity. Controlling inflammation in patients with high IR and coronary inflammation may provide additional benefits.

Efficacy of Internet-Based Cognitive Behavioral Therapy for Subthreshold Depression Among Older Adults in Institutional Long-Term Care Settings: Pragmatic Randomized Controlled Trial.

BACKGROUND: Subthreshold depression (sD) is prevalent in older populations in long-term care (LTC) settings, but psychological therapy in LTC settings in China is not readily available. Thus, internet-based cognitive behavioral therapy (ICBT) may be suitable for this population, but research on the efficacy of ICBT for older adults with sD, especially those living in LTC settings, is limited. OBJECTIVE: This study aimed to evaluate the efficacy and acceptability of ICBT treatment for sD among LTC residents in China. We also examined whether ICBT is as effective as group-based cognitive behavioral therapy (CBT) for treating sD in this population. METHODS: We conducted a pragmatic randomized controlled trial, which included 18 LTC institutions. A total of 354 participants were randomized to ICBT, group-based CBT, or a waiting list and were followed up for 12 months. The primary outcome was self-reported depressive symptoms on the Center for Epidemiological Studies Depression Scale (CES-D). Secondary outcomes were the scores of the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7-Item (GAD-7), and Geriatric Depression Scale (GDS). A mixed-effects model was used to assess the efficacy of ICBT. RESULTS: The ICBT group showed a significant improvement in self-reported depressive symptoms, which was maintained at the 12-month follow-up (all P<.001). The ICBT group exhibited a significantly larger reduction in the scores of the CES-D (Cohen d=0.07, 95% CI 0.04-0.09; P=.01), PHQ-9 (d=0.30, 95% CI 0.28-0.33; P<.001), GDS (d=0.10, 95% CI 0.08-0.13; P<.001), and GAD-7 (d=0.19, 95% CI 0.17-0.22; P<.001) compared with a waiting list at postintervention. ICBT had significantly stronger effects than CBT on the PHQ-9 and GAD-7 at postintervention (d=0.15, 95% CI 0.13-0.17; P<.001 and d=0.21, 95% CI 0.19-0.23; P<.001, respectively), 6-month follow-up (d=0.18, 95% CI 0.16-0.21; P<.001 and d=0.18, 95% CI 0.15-0.21; P<.001, respectively), and 12-month follow-up (d=0.15, 95% CI 0.11-0.19; P<.001 and d=0.18, 95% CI 0.14-0.21; P<.001, respectively). CONCLUSIONS: ICBT is a relatively effective and acceptable intervention for reducing depressive symptoms among Chinese LTC residents with sD. These findings indicate the usefulness of ICBT application for sD in LTC settings. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000030697; https://www.chictr.org.cn/showproj.aspx?proj=50781.

Self-Powered Intelligent Water Droplet Monitoring Sensor Based on Solid-Liquid Triboelectric Nanogenerator.

Real-time monitoring of rainwater is a critical issue in the development of autonomous vehicles and smart homes, while the corresponding sensors play a pivotal role in ensuring their sensitivity. Here, we study a self-powered intelligent water droplet monitoring sensor based on a solid-liquid triboelectric nanogenerator (SL-TENG). The sensor comprises a SL-TENG, a signal acquisition module, a central processing unit (CPU), and a wireless transmission module, facilitating the real-time monitoring of water droplet signals. It is worth noting that the SL-TENG has self-powering characteristics and can convert the kinetic energy of water droplets into electrical energy. The excellent output performance, with open-circuit voltage of 9 V and short-circuit current of 2 µA without any treatment of the SL-TENG, can provide an effective solution to the problem that traditional sensor need battery replacement. In addition, the SL-TENG can generate stable amplitude electrical signals through water droplets, exemplified by the absence of decay in a short-circuit current within 7 days. More importantly, the sensor is equipped with intelligent analytical capabilities, allowing it to assess rainfall based on variables such as amplitude and frequency. Due to its excellent stability and intelligent analysis, this sensor can be used for roof rainwater monitoring, intravenous administration monitoring, and especially in automobile automatic wipers and other fields.

Discovery of Novel 4-Hydroxyquinazoline Derivatives: In Silico, In Vivo and In Vitro Studies Using Primary PARPi-Resistant Cell Lines.

A series of novel 4-Hydroxyquinazoline derivatives were designed and synthesized to enhance sensitivity in primary PARPi-resistant cells. Among them, the compound B1 has been found to have superior cytotoxicity in primary PARPi-resistant HCT-15 and HCC1937 cell lines, and dose-dependently suppressed the intracellular PAR formation and enhanced the γH2AX aggregation. Mechanistic study showed that B1 stimulated the formation of intracellular ROS and the depolarization of the mitochondrial membrane, which could increase apoptosis and cytotoxicity. An in vivo study showed that B1 significantly suppressed tumor growth at a dose of 25 mg/kg, and an acute toxicity study confirmed its safety. Molecular docking and dynamics simulations revealed that hydrogen bonding between B1 and ASP766 may be helpful to enhance anti-drug resistance ability. This study suggests that B1 is a potent PARP inhibitor that can overcome PARPi resistance and deserves further investigation.

Breaking Highly Ordered PtPbBi Intermetallic with Disordered Amorphous Phase for Boosting Electrocatalytic Hydrogen Evolution and Alcohol Oxidation.

Constructing amorphous/intermetallic (A/IMC) heterophase structures by breaking the highly ordered IMC phase with disordered amorphous phase is an effective way to improve the electrocatalytic performance of noble metal-based IMC electrocatalysts because of the optimized electronic structure and abundant heterophase boundaries as active sites. In this study, we report the synthesis of ultrathin A/IMC PtPbBi nanosheets (NSs) for boosting hydrogen evolution reaction (HER) and alcohol oxidation reactions. The resulting A/IMC PtPbBi NSs exhibit a remarkably low overpotential of only 25 mV at 10 mA cm-2 for the HER in an acidic electrolyte, together with outstanding stability for 100 h. In addition, the PtPbBi NSs show high mass activities for methanol oxidation reaction (MOR) and ethanol oxidation reaction (EOR), which are 13.2 and 14.5 times higher than those of commercial Pt/C, respectively. Density functional theory calculations demonstrate that the synergistic effect of amorphous/intermetallic components and multimetallic composition facilitate the electron transfer from the catalyst to key intermediates, thus improving the catalytic activity of MOR. This work establishes a novel pathway for the synthesis of heterophase two-dimensional nanomaterials with high electrocatalytic performance across a wide range of electrochemical applications.

An Effective Approach to Enhance Hydrogen Evolution Reaction and Hydrogen Oxidation Reaction by Ni Doping to MoO3.

The development of bifunctional catalysts that facilitate both the hydrogen evolution reaction (HER) and hydrogen oxidation reaction (HOR) in alkaline environment is crucial for realizing unitized regenerative anion-exchange membrane fuel cells. In this study, a novel strategy to modulate the electron density of MoO3 through Ni doping (sample named Nix Mo1- x O3 ) is reported. Ni is incorporated to replace Mo atoms in MoO3 . Specifically, Nix Mo1- x O3 is combined with optimal adsorption energy, along with MoO2 /Mo2 N hybrid with high conductivity. The resulting Nix Mo1- x O3 supported on MoO2 /Mo2 N hybrid (sample named as Nix Mo1- x O3 -H) exhibits excellent alkaline HER activity, with an overpotential of only 16 mV at 10 mA cm-2 and a Tafel slope of 54 mV dec-1 . In addition, the Nix Mo1- x O3 -H demonstrates an ultrahigh HOR performance with a high exchange current density (3.852 mA cm-2 ). The catalyst's breakdown potential of 0.23 V indicates its ability to withstand higher voltages without breaking down. As evidenced by the results, this characteristic leads to improved stability. These results are higher than those of the other catalysts reported, which indicates that the electron density of MoO3 can be effectively modulated through Ni doping, leading to excellent HER and HOR performance.

Efficacy of an internet-based cognitive behavioral therapy for subthreshold depression among Chinese adults: a randomized controlled trial.

BACKGROUND: Subthreshold depression (sD) negatively impacts well-being and psychosocial function and is more prevalent compared with major depressive disorder (MDD). However, as adults with sD are less likely to seek face-to-face intervention, internet-based cognitive-behavioral therapy (ICBT) may overcome barriers of accessibility to psychotherapy. Although several trials explored the efficacy of ICBT for sD, the results remain inconsistent. This study evaluated whether ICBT is effective in reducing depressive symptoms among Chinese adults with sD. METHODS: A randomized controlled trial was performed. The participants were randomly assigned to 5 weeks of ICBT, group-based face-to-face cognitive-behavioral therapy (CBT), or a waiting list (WL). Assessments were conducted at baseline, post-intervention and at a 6-month follow-up. The primary outcome measured depressive symptoms using the Center for Epidemiological Studies Depression Scale (CES-D). Outcomes were analyzed using a mixed-effects model to assess the effects of ICBT. RESULTS: ICBT participants reported greater reductions on all the outcomes compared to the WL group at post-intervention. The ICBT group showed larger improvement on the Patient Health Questionnaire-9 (PHQ-9) at post-intervention (d = 0.12) and at follow-up (d = 0.10), and with CES-D at post-intervention (d = 0.06), compared to the CBT group. CONCLUSIONS: ICBT is effective in reducing depressive symptoms among Chinese adults with sD, and improvements in outcomes were sustained at a 6-month follow-up. Considering the low rates of face-to-face psychotherapy, our findings highlight the considerable potential and implications for the Chinese government to promote the use of ICBT for sD in China.

TROAP Promotes the Proliferation, Migration, and Metastasis of Kidney Renal Clear Cell Carcinoma with the Help of STAT3.

Kidney renal clear cell carcinoma (KIRC) is a subtype of renal cell carcinoma that threatens human health. The mechanism by which the trophinin-associated protein (TROAP)-an important oncogenic factor-functions in KIRC has not been studied. This study investigated the specific mechanism by which TROAP functions in KIRC. TROAP expression in KIRC was analyzed using the RNAseq dataset from the Cancer Genome Atlas (TCGA) online database. The Mann-Whitney U test was used to analyze the expression of this gene from clinical data. The Kaplan-Meier method was used for the survival analysis of KIRC. The expression level of TROAP mRNA in the cells was detected using qRT-PCR. The proliferation, migration, apoptosis, and cell cycle of KIRC were detected using Celigo, MTT, wound healing, cell invasion assay, and flow cytometry. A mouse subcutaneous xenograft experiment was designed to demonstrate the effect of TROAP expression on KIRC growth in vivo. To further investigate the regulatory mechanism of TROAP, we performed co-immunoprecipitation (CO-IP) and shotgun liquid chromatography-tandem mass spectrometry (LC-MS). TCGA-related bioinformatics analysis showed that TROAP was significantly overexpressed in KIRC tissues and was related to higher T and pathological stages, and a poor prognosis. The inhibition of TROAP expression significantly reduced the proliferation of KIRC, affected the cell cycle, promoted cell apoptosis, and reduced cell migration and invasion. The subcutaneous xenograft experiments showed that the size and weight of the tumors in mice were significantly reduced after TROAP-knockdown. CO-IP and post-mass spectrometry bioinformatics analyses revealed that TROAP may combine with signal transducer and activator of transcription 3 (STAT3) to achieve tumor progression in KIRC; this was verified by functional recovery experiments. TROAP may regulate KIRC proliferation, migration, and metastasis by binding to STAT3.

Lateral Flow Immunoassay Based on Quantum-Dot Nanobeads for Detection of Chloramphenicol in Aquatic Products.

Quantum dot nanobeads (QBs) were used as signal source to develop competitive lateral flow immunoassay (LFIA) for the detection of chloramphenicol (CAP). The quantitative detection of CAP was achieved by calculating the total color difference (∆E) values of the test line (T line) using the images of test strips. QB-based LFIA (QBs-LFIA) allowed the effective dynamic linear detection of CAP in the range of 0.1-1.5 ng/mL. The limit of detection (LOD) was 3.0 ng/mL, which was 50 and 667 times lower than those achieved for two different brands of colloidal gold kits. The recoveries of CAP during real-sample detection were 82.82-104.91% at spiked levels of 0.1, 0.7, and 1.5 ng/mL. These results indicate that the developed QBs-LFIA facilitates the sensitive detection of CAP.

Isolated Electron-Rich Ruthenium Atoms in Intermetallic Compounds for Boosting Electrochemical Nitric Oxide Reduction to Ammonia.

The direct electrochemical nitric oxide reduction reaction (NORR) is an attractive technique for converting NO into NH3 with low power consumption under ambient conditions. Optimizing the electronic structure of the active sites can greatly improve the performance of electrocatalysts. Herein, we prepare body-centered cubic RuGa intermetallic compounds (i.e., bcc RuGa IMCs) via a substrate-anchored thermal annealing method. The electrocatalyst exhibits a remarkable NH4 + yield rate of 320.6 µmol h-1 mg-1 Ru with the corresponding Faradaic efficiency of 72.3 % at very low potential of -0.2 V vs. reversible hydrogen electrode (RHE) in neutral media. Theoretical calculations reveal that the electron-rich Ru atoms in bcc RuGa IMCs facilitate the adsorption and activation of *HNO intermediate. Hence, the energy barrier of the potential-determining step in NORR could be greatly reduced.

Epitaxial Growth of Step-Like Cr2 S3 Lateral Homojunctions Towards Versatile Conduction Polarities and Enhanced Transistor Performances.

For expanding the applications of 2D transition metal dichalcogenides (TMDCs), integrating functional devices with diverse conduction polarities in the same parent material is a very promising direction. Improving the contact issue at the metal-semiconductor interface also holds fundamental significance. To achieve these concurrently, step-like Cr2 S3 vertical stacks with varied thicknesses are achieved via a one-step chemical vapor deposition (CVD) method route. Various types of 2D Cr2 S3 lateral homojunctions are thus naturally evolved, that is, pm -ambipolar/n, p/ambipolar, ambipolar/n, and nm -ambipolar/n junctions, allowing the integration of diverse conduction polarities in single Cr2 S3 homojunctions. Significantly, on-state current density and field-effect mobility of the thinner 2D Cr2 S3 flakes stacked below are detected to be ≈5 and ≈6 times increased in the lateral homojunctions, respectively. This work should hereby provide insights for designing 2D functional devices with simpler structures, for example, multipolar field-effect transistors, photodetectors, and inverters, and provide fundamental references for optimizing the electrical performances of 2D materials related devices.

Quantum Dot Nanobeads as Multicolor Labels for Simultaneous Multiplex Immunochromatographic Detection of Four Nitrofuran Metabolites in Aquatic Products.

A multicolor immunochromatographic assay platform based on quantum dot nanobeads (QBs) for the rapid and simultaneous detection of nitrofuran metabolites in different aquatic products is documented. These metabolites include 3-amino-2-oxazolidinone (AOZ), 1-aminohydantoin (AHD), semicarbazide (SEM), and 3-amino-5-morpholino-methyl-1,3-oxazolidinone (AMOZ). QBs with emission colors of red, yellow, green, and orange were employed and functionalized with the corresponding antibodies to each analyte to develop a multicolor channel. The visual detection limits (cutoff values) of our method for AOZ, AHD, SEM, and AMOZ reached up to 50 ng/mL, which were 2, 20, 20, and 20 times lower than those of traditional colloidal gold test strips, respectively. The test strip is capable of detection within 10 min in real samples while still achieving good stability and specificity. These results demonstrate that the developed multicolor immunochromatographic assay platform is a promising technique for multiplex, highly sensitive, and on-site detection of nitrofuran metabolites.

Effect of substrate symmetry on the orientations of MoS2 monolayers.

Two-dimensional (2D) semiconducting transition metal dichalcogenides (TMDs) are promising platforms for developing next-generation electronic and optoelectronic devices due to their unique properties. To achieve this, the growth of large single-crystal TMDs is a critical issue. Unraveling the factors affecting the nucleation and domain orientation should hold fundamental significance. Herein, we design the chemical vapor deposition growth of monolayer MoS2 triangles on Au(111) and Au(100) facets, for exploring the substrate facet effects on the domain orientations. According to multi-scale characterizations, we find that, the obtained triangular MoS2 domains present two preferential orientations on the six-fold symmetric Au(111) facet, whereas four predominant orientations on the four-fold symmetric Au(100) facet. Using on-site scanning tunneling microscopy, we further reveal the preferred alignments of monolayer MoS2 triangles along the close-packed directions of both Au(111) and Au(100) facets. Moreover, bunched substrate steps are also found to form along the close-packed directions of the crystal facets, which guides the preferential nucleation of monolayer MoS2 along the step edges. This work should hereby deepen the understanding of the substrate facet/step effect on the nucleation and orientation of monolayer MoS2 domains, thus providing fundamental insights into the controllable syntheses of large single-crystal TMD monolayers.

Diabetes aggravates myocardial ischaemia reperfusion injury via activating Nox2-related programmed cell death in an AMPK-dependent manner.

Cardiovascular diseases such as myocardial ischaemia have a high fatality rate in patients with diabetes. This study was designed to expose the crosstalk between oxidative stress and AMPK, a vital molecule that controls biological energy metabolism, in myocardial ischaemia reperfusion injury (I/RI) in diabetic rats. Diabetes was stimulated in rats using streptozotocin injection. Rats were separated on random into control, control + I/R, Diabetes, Diabetes + I/R, Diabetes + I/R + N-acetylcysteine and Diabetes + I/R + Vas2870 groups. Myocardial infarct size was determined, and the predominant Nox family isoforms were analysed. In vitro, the H9C2 cells were administered excess glucose and exposed to hypoxia/reoxygenation to mimic diabetes and I/R. The AMPK siRNA or AICAR was used to inhibit or activate AMPK expression in H9C2 cells, respectively. Then, myocardial oxidative stress and programmed cell death were measured. Diabetes or high glucose levels were found to aggravate myocardial I/RI or hypoxia/reoxygenation in H9C2 cells, as demonstrated by an increase in myocardial infarct size or lactate dehydrogenase levels, oxidative stress generation and induction of programmed cell death. In diabetic rat hearts, cardiac Nox1, Nox2 and Nox4 were all heightened. The suppression of Nox2 expression using Vas2870 or Nox2-siRNA treatment in vivo or in vitro, respectively, protected diabetic rats from myocardial I/RI. AMPK gene knockout increased Nox2 protein expression while AMPK agonist decreased Nox2 expression. Therefore, diabetes aggravates myocardial I/RI by generating of Nox2-associated oxidative stress in an AMPK-dependent manner, which led to the induction of programmed cell death such as apoptosis, pyroptosis and ferroptosis.

MicroRNA-2861 and microRNA-5115 regulates myocardial ischemia-reperfusion injury through the GPR30/mTOR signaling pathway by binding to GPR30.

Myocardial ischemia-reperfusion (I/R) injury, a major contributor to morbidity and mortality, represents a combination of intrinsic cellular response to ischemia and the extrinsic acute inflammatory response. In the present study, microarray analysis of GSE67308 and GSE50885 identified differentially expressed GPR30 and upstream regulatory miR-2861 and miR-5115 in myocardial I/R. Furthermore, GPR30 was confirmed as a common target gene of miR-2861 and miR-5115, and miR-2861 and miR-5115 inhibited GPR30 expression. Poor expression of GPR30 was identified in the myocardial I/R injury mouse model. Overexpressed GPR30 led to alleviated the pathological conditions, diminished myocardial infarct size and apoptosis of myocardial tissue in mice. Moreover, miR-2861 and miR-5115 were found to be highly expressed in the myocardial I/R injury mouse model and to subsequently accelerate the disease progression. Notably, PR30 curtailed the development of myocardial I/R injury through activation of the mTOR signaling pathway. The key findings suggested that miR-2861 and miR-5115 blocked the activation of the GPR30/mTOR signaling pathway by targeting GPR30, thereby accelerating myocardial I/R injury in mice.

MMP9, CXCR1, TLR6, and MPO participant in the progression of coronary artery disease.

Coronary artery disease (CAD) is the most frequent cardiovascular disease, which is induced by the decreased myocardial blood supply. The present study is conducted to understand the mechanisms of CAD. The GSE98583, GSE69587, and GSE71226 datasets from the Gene Expression Omnibus database were obtained. The differentially expressed genes (DEGs) were analyzed by the limma package, then the DEGs appeared in two or three datasets were selected as the coregulated genes using the VENNY tool, followed by enrichment analysis using DAVID tool. Protein-protein interaction (PPI) network, microRNA-transcription factor-target regulatory network, and drug-gene network were visualized. Finally, quantitative PCR and dual-luciferase reporter assay were conducted to validate the expression of key genes and the target relationship. There were 221 coregulated genes in GSE98583, GSE69587, and GSE71226. Besides, four pathways and 23 functional terms for co-upregulated genes, and 11 functional terms for co-downregulated genes were enriched. The degrees of PPI network nodes matrix metallopeptidase 9 (MMP9), C-X-C motif chemokine receptor 1 (CXCR1), toll-like receptor 6 (TLR6), and myeloperoxidase (MPO) were relatively higher. Moreover, MPO could interact with MMP9, CXCR1, and TLR6 in the PPI network. In the regulatory network, TLR6 and MMP9 separately were targeted by miR-3960 and v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA). Additionally, MMP9, CXCR1, and MPO were involved in the drug-gene network. The expression of MMP9, CXCR1, TLR6, and MPO were significantly upregulated in CAD samples than control, and miR-3960 could bind to TLR6 to inhibit its expression. CXCR1 and MPO might be involved in the progression of CAD. Besides, miR-3960 might function in the pathogenesis of CAD through targeting TLR6, and RELA might exert its role in CAD via targeting MMP9.

Association of C-reactive protein (CRP) rs1205 and rs2808630 variants and risk of cancer.

The correlation between rs1205, rs2808630 variants of C-reactive protein (CRP) gene and susceptibility of cancer has been assessed previously, but with conflicting results. We adopted odds ratios (ORs) with 95% confidence intervals (CIs), in silico tools and enzyme-linked immunosorbent assay (ELISA) analysis to evaluate this association. Totally, 10,614 cancer subjects and 33,294 controls were involved in the pooled analysis. When all the studies were pooled, no significant correlation was indicated between the two variants and cancer risk. However, in stratification analysis by ethnicity, we found that CRP rs1205 C>T polymorphism was associated with an elevated risk of cancer in Asians (T-allele vs. C-allele, OR = 1.20, 95% CI = 1.06-1.36, pheterogeneity = .226; TT vs. CC, OR = 1.48, 95% CI = 1.14-1.93, pheterogeneity = .089). Similar findings were observed for rs2808630 variant. In silico tools showed that lung adenocarcinoma participants with high CRP expression may have shorter overall survival time than low expression group. ELISA analysis indicated that CRP expression in prostate adenocarcinoma subjects with TT + TC genotypes was statistically higher than in those with CC genotypes. CRP rs1205 C>T and rs2808630 T>C polymorphism may be associated with cancer risk, especially for Asians.

Atherosclerosis-associated endothelial cell apoptosis by miRNA let7-b-mediated downregulation of HAS-2.

MicroRNAs (miRNAs) play essential roles in the regulation and pathophysiology of various types of human diseases including atherosclerosis. Increasing numbers of miRNAs have been identified to be important regulators in the progression of atherosclerosis by regulating gene expression. However, functional miRNAs and the underlying mechanisms involved in atherosclerosis need fully elucidation. In the present study, the function of miRNA let-7b was investigated in human aortic endothelial cells (HAECs). The results showed that downregulation of let-7b in the high-fat diet mice and HAECs was inversely correlated with the expression level of HAS-2. upregulation of let-7b significantly reduced apoptosis of HAECs. The results also revealed that HAS-2 was a target gene of let-7b and HAS-2 reduction reversed the antiapoptotic effect of let-7b through regulation of the P13K/Akt pathway. These results together suggest the potential of regulating the let-7b expression and endothelial apoptosis against development and progression of atherosclerosis.