Heavy Metal Exposure and Cardiovascular Disease.

Heavy metals are harmful environmental pollutants that have attracted widespread attention due to their health hazards to human cardiovascular disease. Heavy metals, including lead, cadmium, mercury, arsenic, and chromium, are found in various sources such as air, water, soil, food, and industrial products. Recent research strongly suggests a connection between cardiovascular disease and exposure to toxic heavy metals. Epidemiological, basic, and clinical studies have revealed that heavy metals can promote the production of reactive oxygen species, which can then exacerbate reactive oxygen species generation and induce inflammation, resulting in endothelial dysfunction, lipid metabolism distribution, disruption of ion homeostasis, and epigenetic changes. Over time, heavy metal exposure eventually results in an increased risk of hypertension, arrhythmia, and atherosclerosis. Strengthening public health prevention and the application of chelation or antioxidants, such as vitamins and beta-carotene, along with minerals, such as selenium and zinc, can diminish the burden of cardiovascular disease attributable to metal exposure.

Enhanced Light Absorption and Photo-Generated Charge Separation Efficiency for Boosting Photocatalytic H2 Evolution through TiO2 Quantum Dots with N-Doping and Concomitant Oxygen Vacancy.

Low-range light absorption and rapid recombination of photo-generated charge carriers have prevented the occurrence of effective and applicable photocatalysis for decades. Quantum dots (QDs) offer a solution due to their size-controlled photon properties and charge separation capabilities. Herein, well-dispersed interstitial nitrogen-doped TiO2 QDs with stable oxygen vacancies (N-TiO2-x-VO) are fabricated by using a low-temperature, annealing-assisted hydrothermal method. Remarkably, electrostatic repulsion prevented aggregation arising from negative charges accumulated in situ on the surface of N-TiO2-x-VO, enabling complete solar spectrum utilization (200-800 nm) with a 2.5 eV bandgap. Enhanced UV-vis photocatalytic H2 evolution rate (HER) reached 2757 µmol g-1 h-1, 41.6 times higher than commercial TiO2 (66 µmol g-1 h-1). Strikingly, under visible light, HER rate was 189 µmol g-1 h-1. Experimental and simulated studies of mechanisms reveal that VO can serve as an electron reservoir of photo-generated charge carriers on N-doped active sites, and consequently, enhance the separation rate of exciton pairs. Moreover, the negative free energy (-0.35 V) indicates more favorable thermodynamics for HER as compared with bulk TiO2 (0.66 V). This research work paves a new way of developing efficient photocatalytic strategies of HER that are applicable in the sustainable carbon-zero energy supply.

What do cancer survivors believe caused their cancer? A secondary analysis of cross-sectional survey data.

PURPOSE: Given that risk reduction and healthy lifestyles can prevent 4 in 10 cancers, it is important to understand what survivors believe caused their cancer to inform educational initiatives. METHODS: In this secondary analysis, we analyzed cancer survivor responses on the Causes Subscale of the Revised Illness Perception Questionnaire, which lists 18 possible causes of illness and a free text question. We used descriptive statistics to determine cancer survivors' agreement with the listed causes and conducted separate partial proportional odds models for the top three causes to examine their associations with sociodemographic and clinical characteristics. Content analysis was used to examine free text responses. RESULTS: Of the 1,001 participants, most identified as Caucasian (n = 764, 77%), female (n = 845, 85%), and were diagnosed with breast cancer (n = 656, 66%). The most commonly believed causes of cancer were: stress or worry (n = 498, 51%), pollution in the environment (n = 471, 48%), and chance or bad luck (n = 412, 42%). The associations of sociodemographic and clinical variables varied across the models. Free text responses indicated that hereditary and genetic causes (n = 223, 22.3%) followed by trauma and stress (n = 218, 21.8%) and bad luck or chance (n = 79, 7.9%) were the most important causes of cancer. CONCLUSIONS: Study results illuminate cancer survivors' beliefs about varying causes of their cancer diagnosis and identify characteristics of survivors who are more likely to believe certain factors caused their cancer. Results can be used to plan cancer education and risk-reduction campaigns and highlight for whom such initiatives would be most suitable.

Human-Induced Pluripotent Stem Cell-Based Differentiation of Cardiomyocyte Subtypes for Drug Discovery and Cell Therapy.

Drug attrition rates have increased over the past few years, accompanied with growing costs for the pharmaceutical industry and consumers. Lack of in vitro models connecting the results of toxicity screening assays with clinical outcomes accounts for this high attrition rate. The emergence of cardiomyocytes derived from human pluripotent stem cells provides an amenable source of cells for disease modeling, drug discovery, and cardiotoxicity screening. Functionally similar to to embryonic stem cells, but with fewer ethical concerns, induced pluripotent stem cells (iPSCs) can recapitulate patient-specific genetic backgrounds, which would be a huge revolution for personalized medicine. The generated iPSC-derived cardiomyocytes (iPSC-CMs) represent different subtypes including ventricular-, atrial-, and nodal-like cardiomyocytes. Purifying these subtypes for chamber-specific drug screening presents opportunities and challenges. In this chapter, we discuss the strategies for the purification of iPSC-CMs, the use of iPSC-CMs for drug discovery and cardiotoxicity test, and the current limitations of iPSC-CMs that should be overcome for wider and more precise cardiovascular applications.

High-efficiency photoreduction of CO2 in a low vacuum.

Photoreduction of CO2 into CO, CH4 or hydrocarbons is attractive, due to environmental compatibility and economic feasibility. Optimizing the reaction engineering of CO2 reduction is an effective and general strategy that should be given special consideration. In this article, the photocatalytic CO2 reduction performances are originally investigated in a low vacuum in both dilute (10%) and pure CO2. We discover that the CH4 yield increased above one hundred times as the vacuum degree increased from barometric pressure to -80 kPa in dilute CO2. It also reveals long-term stability and good cycling performance in a low vacuum. The enhanced CO2 photoreduction performance in a low vacuum comes from better accumulation of photogenerated electrons, less intense Brownian movement of gas molecules in the environment and hindrance of the active site-blocking of gas molecules in the environment. Improved photocatalytic CO2 reduction in a low vacuum is further verified by Pt-TiO2 catalysts. This research presents a general route for producing clean fuels by photocatalytic CO2 reduction in a more effective way.

Human-induced pluripotent stem cells as models for rare cardiovascular diseases: from evidence-based medicine to precision medicine.

Rare cardiovascular diseases (RCDs) refer to those cardiovascular diseases that display a low prevalence as well as morbidity. Due to the vast variety of underlying genetic mutations and the relatively low patient population, RCDs present additional challenges for diagnosis. Precision medicine may offer opportunities for designing patient-specific therapies in particular for carriers of variants with undetermined significance. Moreover, precision medicine strategies provide benefit to patients with "common" symptoms but carry in rare genetic variants. Induced pluripotent stem cells (iPSCs) present a state-of-the-art precision medicine approach which recently made contributions to the study of RCDs via patient-specific iPSC-derived cardiomyocytes (iPSC-CMs). Human iPSC-CMs are derived from a patient's somatic cells and thus recapitulate a personalized genomics background, serving as patient-specific disease models. In light of these advantages, iPSC-CMs evolved as an effective tool for modeling cardiac disease phenotypes and accurately evaluating the toxicity of potential therapeutic compounds. This review covers approaches for studying RCDs and iPSC-CM models generated so far for different RCDs, such as long QT syndrome (LQT), short QT syndrome (SQT), Brugada syndrome (BrS), arrhythmogenic right ventricular cardiomyopathy (ARVC), and other rare diseases accomplished by cardiac-related syndromes like Fabry disease (FD) and Marfan syndrome (MFS). This overview aims to aid better understanding of the utility of iPSC-CM models, their various features, and future prospects.

Wrinkle-free atomically thin CdS nanosheets for photocatalytic hydrogen evolution.

Two-dimensional (2D) nanosheets of atomic thickness have attracted extensive research interest recently. In this work, atomically thin (0.7 nm) flat CdS (F-CdS) nanosheets of several tens of micrometers in lateral size were synthesized by a solvent-thermal method. The as-synthesized F-CdS could maintain flat morphology well in solution, while irreversible wrinkles could be generated after drying, forming wrinkled CdS (W-CdS) samples. It was revealed that the formation of wrinkles could reduce light absorbance, narrow the band gap, move down the conduction band position and accelerate electron-hole recombination. As photocatalysts, the F-CdS achieved a photocatalytic H2 evolution rate of 138.7 mmol g-1 h-1 without any co-catalyst under visible light, which was much higher than that of the W-CdS sample (with an H2 evolution rate of only 52.8 mmol g-1 h-1). This work demonstrates that great attention should be paid to the wrinkles in 2D materials as photocatalysts.

Enhanced photocatalytic oxygen evolution activity by formation of Ir@IrOx(OH)y core-shell heterostructure.

Developing efficient catalysts to accelerate the rate of oxygen evolution reaction (OER) is critical for photocatalytic water-splitting. In this work, metallic Ir, IrOx(OH)y, and core-shell Ir@IrOx(OH)y were synthesized and employed as OER catalysts for photocatalytic water oxidation. It was found that the Ir@IrOx(OH)y core-shell heterostructure catalyst showed the best photocatalytic performance among these three catalysts, with the oxygen evolution rate as high as 59.63 mmol g-1 h-1. Detailed investigations revealed that the excellent photocatalytic activity of Ir@IrOx(OH)y could be attributed to both the outstanding intrinsic activity of IrOx(OH)y shell and the efficient electron transfer between the photosensitizer and catalyst.

Composition-dependent activity of Mn-doping NiS2 nanosheets for boosting photocatalytic H2 evolution.

Two-dimensional transition metal disulfides are excellent photocatalytic materials, which can be significantly improved by optimizing the composition and structure. Herein, Mn-doping NiS2 of (Ni1-xMnx)-S with various Ni/Mn molar ratios is proposed via a facile and low-cost solvothermal method. The optimal (Ni4/6Mn2/6)-S exhibits pinecone-like morphology composed of tiny nanosheets with enlarged active sites, which facilitates the separation of photoinduced electrons and holes, improves the electron transfer ability and conductivity, and enlarges the active sites compared with pure NiS2 and MnS. Also, the negative shift of the conduction band derived from Mott-Schottky plots and the empirical formula provides a high thermodynamic driving force for hydrogen catalytic reaction. (Ni4/6Mn2/6)-S performs an ultrahigh hydrogen evolution rate of 24.86 mmol g-1 h-1 under UV-visible light irradiation, which is 1.5 times higher than pure NiS2 (16.92 mmol g-1 h-1) and 2.3 times higher than pure MnS (10.69 mmol g-1 h-1). The outstanding repeatability of 86.7% retention and apparent quantum yield of 46.9% are also achieved. Therefore, this work offers a novel bimetallic sulfide of (Ni1-xMnx)-S to improve the conversion efficiency of solar energy to chemical energy for photocatalytic hydrogen production.

Interchromosomal interaction of homologous Stat92E alleles regulates transcriptional switch during stem-cell differentiation.

Pairing of homologous chromosomes in somatic cells provides the opportunity of interchromosomal interaction between homologous gene regions. In the Drosophila male germline, the Stat92E gene is highly expressed in a germline stem cell (GSC) and gradually downregulated during the differentiation. Here we show that the pairing of Stat92E is always tight in GSCs and immediately loosened in differentiating daughter cells, gonialblasts (GBs). Disturbance of Stat92E pairing by relocation of one locus to another chromosome or by knockdown of global pairing/anti-pairing factors both result in a failure of Stat92E downregulation, suggesting that the pairing is required for the decline in transcription. Furthermore, the Stat92E enhancer, but not its transcription, is required for the change in pairing state, indicating that pairing is not a consequence of transcriptional changes. Finally, we show that the change in Stat92E pairing is dependent on asymmetric histone inheritance during the asymmetric division of GSCs. Taken together, we propose that the changes in Stat92E pairing status is an intrinsically programmed mechanism for enabling prompt cell fate switch during the differentiation of stem cells.

Fusion Bonding Possibility for Incompatible Polymers by the Novel Ultrasonic Welding Technology: Effect of Interfacial Compatibilization.

Fusion bonding for polymers has been successfully welded for the same and dissimilar materials. However, it is difficult to bond incompatible polymers due to poor interfacial adhesion. Usually, interfacial compatibilization can resolve this problem. According to the mechanism, an interlayer solder sheet (ISS) consisting of maleic anhydride-functionalized polypropylene (PP-g-MAH) and polyamide6 (PA6) was introduced into the ultrasonic welding (USW) device. In this way, it successfully realized the weldability between PP and PA6. The welding strength of PP-PA6 reached 22.3 MPa, about 84% welding strength for the PP body and 63% tensile strength for PP. Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), and scanning electron microscopy (SEM) showed the formation of PP-g-PA6 copolymer in blends. This copolymer played the role of an emulsifier, which enhanced the interfacial adhesion between PP and PA6 in two phases, leading to micron-scale homogeneity. In the USW process, the copolymer could act as a bridge between PP and PA6 molecular chains to realize the fusion bonding of incompatible polymers. Finally, we proposed the fusion bonding model for PP-PA6 interfaces.

Generation of an induced pluripotent stem cell line from a patient carrying FBN1/c.6734 G > A mutation.

Mutations in FBN1 (gene encodes the matrix protein fibrillin 1), are usually associated with Marfan syndrome (MS). This syndrome contains ocular, skeletal, cardiovascular, pulmonary, cutaneous and neurological abnormalities. Here, we introduced an induced pluripotent stem cell (iPSC) line from a patient who suffered from severe cardiovascular disease and carried a c.6734G > A mutation in FBN1. Dermal fibroblasts of the patient were reprogrammed with non-integrating Sendai virus (SeV). Generated iPSC line exhibited normal karyotype, showed embryonic stem cell-like morphology, expressed pluripotency markers, and was capable of differentiating into three germ layers. This iPSC line will be a valuable tool for studying MS.

DNA methylation-calling tools for Oxford Nanopore sequencing: a survey and human epigenome-wide evaluation.

BACKGROUND: Nanopore long-read sequencing technology greatly expands the capacity of long-range, single-molecule DNA-modification detection. A growing number of analytical tools have been developed to detect DNA methylation from nanopore sequencing reads. Here, we assess the performance of different methylation-calling tools to provide a systematic evaluation to guide researchers performing human epigenome-wide studies. RESULTS: We compare seven analytic tools for detecting DNA methylation from nanopore long-read sequencing data generated from human natural DNA at a whole-genome scale. We evaluate the per-read and per-site performance of CpG methylation prediction across different genomic contexts, CpG site coverage, and computational resources consumed by each tool. The seven tools exhibit different performances across the evaluation criteria. We show that the methylation prediction at regions with discordant DNA methylation patterns, intergenic regions, low CG density regions, and repetitive regions show room for improvement across all tools. Furthermore, we demonstrate that 5hmC levels at least partly contribute to the discrepancy between bisulfite and nanopore sequencing. Lastly, we provide an online DNA methylation database ( https://nanome.jax.org ) to display the DNA methylation levels detected by nanopore sequencing and bisulfite sequencing data across different genomic contexts. CONCLUSIONS: Our study is the first systematic benchmark of computational methods for detection of mammalian whole-genome DNA modifications in nanopore sequencing. We provide a broad foundation for cross-platform standardization and an evaluation of analytical tools designed for genome-scale modified base detection using nanopore sequencing.

Removal of Hg2+ with Polypyrrole-Functionalized Fe3O4/Kaolin: Synthesis, Performance and Optimization with Response Surface Methodology.

PPy-Fe3O4/Kaolin was prepared with polypyrrole functionalized magnetic Kaolin by a simple, green, and low cost method to improve the agglomeration and low adsorption capacity of Kaolin. PPy-Fe3O4/Kaolin was employed to remove Hg2+ and the results were characterized by various methods. Relevant factors, including solution pH, dosage of adsorbent, concentration (C0), and temperature (T), were optimized by Response Surface Methodology (RSM) and Central Composite Designs (CCD). The optimal results show that the importance for adsorption factors is pH > T > C0 > dosage, and the optimal adsorption conditions of PPy-Fe3O4/Kaolin are pH = 7.2, T = 315 K, C0 = 50 mg/L, dosage of 0.05 g/L, and the capacity is 317.1 mg/g. The adsorption process conforms to the pseudo-second-order and Langmuir models. Dubinin-Radushkevich model shows that adsorption process is spontaneous and endothermic. Moreover, the adsorption of mercury by PPy-Fe3O4/Kaolin was achieved mainly through electrostatic attraction, pore diffusion, and chelation between amino functional groups and Hg2+. PPy-Fe3O4/Kaolin has excellent reproducibility, dispersity, and chemical stability, and it is easy to be separated from solution through an external magnetic field. The experiments show that PPy-Fe3O4/Kaolin is an efficient and economical adsorbent towards mercury.

CUP-AI-Dx: A tool for inferring cancer tissue of origin and molecular subtype using RNA gene-expression data and artificial intelligence.

BACKGROUND: Cancer of unknown primary (CUP), representing approximately 3-5% of all malignancies, is defined as metastatic cancer where a primary site of origin cannot be found despite a standard diagnostic workup. Because knowledge of a patient's primary cancer remains fundamental to their treatment, CUP patients are significantly disadvantaged and most have a poor survival outcome. Developing robust and accessible diagnostic methods for resolving cancer tissue of origin, therefore, has significant value for CUP patients. METHODS: We developed an RNA-based classifier called CUP-AI-Dx that utilizes a 1D Inception convolutional neural network (1D-Inception) model to infer a tumor's primary tissue of origin. CUP-AI-Dx was trained using the transcriptional profiles of 18,217 primary tumours representing 32 cancer types from The Cancer Genome Atlas project (TCGA) and International Cancer Genome Consortium (ICGC). Gene expression data was ordered by gene chromosomal coordinates as input to the 1D-CNN model, and the model utilizes multiple convolutional kernels with different configurations simultaneously to improve generality. The model was optimized through extensive hyperparameter tuning, including different max-pooling layers and dropout settings. For 11 tumour types, we also developed a random forest model that can classify the tumour's molecular subtype according to prior TCGA studies. The optimised CUP-AI-Dx tissue of origin classifier was tested on 394 metastatic samples from 11 tumour types from TCGA and 92 formalin-fixed paraffin-embedded (FFPE) samples representing 18 cancer types from two clinical laboratories. The CUP-AI-Dx molecular subtype was also independently tested on independent ovarian and breast cancer microarray datasets FINDINGS: CUP-AI-Dx identifies the primary site with an overall top-1-accuracy of 98.54% in cross-validation and 96.70% on a test dataset. When applied to two independent clinical-grade RNA-seq datasets generated from two different institutes from the US and Australia, our model predicted the primary site with a top-1-accuracy of 86.96% and 72.46% respectively. INTERPRETATION: The CUP-AI-Dx predicts tumour primary site and molecular subtype with high accuracy and therefore can be used to assist the diagnostic work-up of cancers of unknown primary or uncertain origin using a common and accessible genomics platform. FUNDING: NIH R35 GM133562, NCI P30 CA034196, Victorian Cancer Agency Australia.

Enhanced photocatalytic hydrogen evolution from in situ formation of few-layered MoS2/CdS nanosheet-based van der Waals heterostructures.

Here we report for the first time that the H2 bubbles generated by photocatalytic water splitting are effective in the layer-by-layer exfoliation of MoS2 nanocrystals (NCs) into few layers. The as-obtained few layers can be in situ assembled with CdS nanosheets (NSs) into van der Waals heterostructures (vdWHs) of few-layered MoS2/CdS NSs which, in turn, are effective in charge separation and transfer, leading to enhanced photocatalytic H2 production activity. The few-layered MoS2/CdS vdWHs exhibited a H2 evolution rate of 140 mmol g(CdS)-1 h-1 and achieved an apparent quantum yield of 66% at 420 nm.

Evaluation of molecules based on the electron donor-acceptor architecture as near-infrared ß-amyloidal-targeting probes.

A novel class of near-infrared molecules based on the donor-acceptor architecture were synthesized and evaluated as Aß imaging probes. In vivo imaging studies suggested that MCAAD-3 could penetrate the blood-brain barrier and label Aß plaques in the brains of transgenic mice. Computational studies could reproduce the experimental trends well.