NAT10 Is Involved in Cardiac Remodeling Through ac4C-Mediated Transcriptomic Regulation.

BACKGROUND: Heart failure, characterized by cardiac remodeling, is associated with abnormal epigenetic processes and aberrant gene expression. Here, we aimed to elucidate the effects and mechanisms of NAT10 (N-acetyltransferase 10)-mediated N4-acetylcytidine (ac4C) acetylation during cardiac remodeling. METHODS: NAT10 and ac4C expression were detected in both human and mouse subjects with cardiac remodeling through multiple assays. Subsequently, acetylated RNA immunoprecipitation and sequencing, thiol-linked alkylation for the metabolic sequencing of RNA (SLAM-seq), and ribosome sequencing (Ribo-seq) were employed to elucidate the role of ac4C-modified posttranscriptional regulation in cardiac remodeling. Additionally, functional experiments involving the overexpression or knockdown of NAT10 were conducted in mice models challenged with Ang II (angiotensin II) and transverse aortic constriction. RESULTS: NAT10 expression and RNA ac4C levels were increased in in vitro and in vivo cardiac remodeling models, as well as in patients with cardiac hypertrophy. Silencing and inhibiting NAT10 attenuated Ang II-induced cardiomyocyte hypertrophy and cardiofibroblast activation. Next-generation sequencing revealed ac4C changes in both mice and humans with cardiac hypertrophy were associated with changes in global mRNA abundance, stability, and translation efficiency. Mechanistically, NAT10 could enhance the stability and translation efficiency of CD47 and ROCK2 transcripts by upregulating their mRNA ac4C modification, thereby resulting in an increase in their protein expression during cardiac remodeling. Furthermore, the administration of Remodelin, a NAT10 inhibitor, has been shown to prevent cardiac functional impairments in mice subjected to transverse aortic constriction by suppressing cardiac fibrosis, hypertrophy, and inflammatory responses, while also regulating the expression levels of CD47 and ROCK2 (Rho associated coiled-coil containing protein kinase 2). CONCLUSIONS: Therefore, our data suggest that modulating epitranscriptomic processes, such as ac4C acetylation through NAT10, may be a promising therapeutic target against cardiac remodeling.

Nuclear import of Mas-related G protein-coupled receptor member D induces pathological cardiac remodeling.

Alamandine (Ala), a ligand of Mas-related G protein-coupled receptor, member D (MrgD), alleviates angiotensin II (AngII)-induced cardiac hypertrophy. However, the specific physiological and pathological role of MrgD is not yet elucidated. Here, we found that MrgD expression increased under various pathological conditions. Then, MrgD knockdown prevented AngII-induced cardiac hypertrophy and fibrosis via inactivating Gαi-mediacted downstream signaling pathways, including the phosphorylation of p38 (p-P38), while MrgD overexpression induced pathological cardiac remodeling. Next, Ala, like silencing MrgD, exerted its cardioprotective effects by inhibiting Ang II-induced nuclear import of MrgD. MrgD interacted with p-P38 and promoted its entry into the nucleus under Ang II stimulation. Our results indicated that Ala was a blocking ligand of MrgD that inhibited downstream signaling pathway, which unveiled the promising cardioprotective effect of silencing MrgD expression on alleviating cardiac remodeling. Video Abstract.

Oxidation of tetracycline hydrochloride with a photoenhanced MIL-101(Fe)/g-C3N4/PMS system: Synergetic effects and radical/nonradical pathways.

MIL-101(Fe)-based catalysts have been widely used for degradation of organic pollutants based on peroxymonosulfate (PMS) activation. Hence, a facile calcination and hydrothermal method was used in this study to prepare a MIL-101(Fe)/g-C3N4 composite catalyst with high activity and high stability for PMS activation to degrade tetracycline hydrochloride (TC) under visible-light irradiation. We clearly elucidated the mechanism involved in the MIL-101(Fe)/g-C3N4 photo Fenton-catalyzed PMS activation process by separating the PMS activation and pollutant oxidation processes. The synergetic effects of MIL-101(Fe) and g-C3N4 involved MIL-101(Fe) acting as an electron shuttle mediating electron transfer from the organic substrate to PMS, accompanied by redox cycling of the surface Fe(II)/Fe(III). Multiple experimental results indicated that PMS was bound to the surface of MIL-101(Fe)/g-C3N4 during visible irradiation and generation of sulfate radicals (SO4•-), hydroxyl radicals (•OH) and superoxide anion free radicals (•O2-) for the radical pathway and singlet oxygen (1O2) and holes (h+) for the nonradical pathway. The major degradation pathways for TC can be described as demethylation, deamination, deamidation and carbonylation. This work provides valuable information and advances the fundamental understanding needed for design and syntheses of metal-free conjugated polymers modified by metal-organic frameworks for heterogeneous photo-Fenton reactions.

In Situ Synthesis of Doped Bio-Graphenes as Effective Metal-Free Catalysts in Removal of Antibiotics: Effect of Natural Precursor on Doping, Morphology, and Catalytic Activity.

Wastewater contaminated with antibiotics is a major environmental challenge. The oxidation process is one of the most common and effective ways to remove these pollutants. The use of metal-free, green, and inexpensive catalysts can be a good alternative to metal-containing photocatalysts in environmental applications. We developed here the green synthesis of bio-graphenes by using natural precursors (Xanthan, Chitosan, Boswellia, Tragacanth). The use of these precursors can act as templates to create 3D doped graphene structures with special morphology. Also, this method is a simple method for in situ synthesis of doped graphenes. The elements present in the natural biopolymers (N) and other elements in the natural composition (P, S) are easily placed in the graphene structure and improve the catalytic activity due to the structural defects, surface charges, increased electron transfers, and high absorption. The results have shown that the hollow cubic Chitosan-derived graphene has shown the best performance due to the doping of N, S, and P. The Boswellia-derived graphene shows the highest surface area but a lower catalytic performance, which indicates the more effective role of doping in the catalytic activity. In this mechanism, O2 dissolved in water absorbs onto the positively charged C adjacent to N dopants to create oxygenated radicals, which enables the degradation of antibiotic molecules. Light irradiation increases the amount of radicals and rate of antibiotic removal.

Enriched Surface Oxygen Vacancies of Fe2(MoO4)3 Catalysts for a PDS-Activated photoFenton System.

The environmentally benign Fe2(MoO4)3 plays a crucial role in the transformation of organic contaminants, either through catalytically decomposing oxidants or through directly oxidizing the target pollutants. Because of their dual roles and the complex surface chemical reactions, the mechanism involved in Fe2(MoO4)3-catalyzed PDS activation processes remains obscure. In this study, Fe2(MoO4)3 was prepared via the hydrothermal and calcine method, and photoFenton degradation of methyl orange (MO) was used to evaluate the catalytic performance of Fe2(MoO4)3. Fe2(MoO4)3 catalysts with abundant surface oxygen vacancies were used to construct a synergistic system involving a photocatalyst and PDS activation. The oxygen vacancies and Fe2+/Fe3+ shuttle played key roles in the novel pathways for generation of •O2-, h+, and 1O2 in the UV-Vis + PDS + FMO-6 photoFenton system. This study advances the fundamental understanding of the underlying mechanism involved in the transition metal oxide-catalyzed PDS activation processes.

Efficient Degradation of Congo Red in Water by UV-Vis Driven CoMoO4/PDS Photo-Fenton System.

In order to improve the catalytic activity of cobalt molybdate (CoMoO4), a PDS-activated and UV-vis assisted system was constructed. CoMoO4 was prepared by coprecipitation and calcination, and characterized by XRD, FTIR, Raman, SEM, TEM, XPS, TGA Zeta potential, BET, and UV-Vis DRS. The results showed that the morphology of the CoMoO4 nanolumps consisted of stacked nanosheets. XRD indicated the monoclinic structures with C2/m (C32h, #12) space group, which belong to α-CoMoO4, and both Co2+ and Mo6+ ions occupy distorted octahedral sites. The pH of the isoelectric point (pHIEP) of CMO-8 at pH = 4.88 and the band gap of CoMoO4 was 1.92 eV. The catalytic activity of CoMoO4 was evaluated by photo-Fenton degradation of Congo red (CR). The catalytic performance was affected by calcination temperature, catalyst dosage, PDS dosage, and pH. Under the best conditions (0.8 g/L CMO-8, PDS 1 mL), the degradation efficiency of CR was 96.972%. The excellent catalytic activity of CoMoO4 was attributed to the synergistic effect of photo catalysis and CoMoO4-activated PDS degradation. The capture experiments and the ESR showed that superoxide radical (·O2-), singlet oxygen (1O2), hole (h+), sulfate (SO4-·), and hydroxyl (·OH-) were the main free radicals leading to the degradation of CR. The results can provide valuable information and support for the design and application of high-efficiency transition metal oxide catalysts.

Pellino1 deficiency reprograms cardiomyocytes energy metabolism in lipopolysaccharide-induced myocardial dysfunction.

Pellino1 has been shown to regulate proinflammatory genes by activating the nuclear factor kappa B (NF-κB) and Toll-like receptor (TLR) signaling pathways, which are important in the pathological development of lipopolysaccharide (LPS)-induced myocarditis. However, it is still unknown whether silencing Pellino1 (si-Pellino1) has a therapeutic effect on this disease. Here, we showed that silencing Pellino1 can be a potential protective strategy for abnormal myocardial energy metabolism in LPS-induced myocarditis. We used liquid chromatography electrospray-ionization tandem mass spectrometry (LC-MS/MS) to analyze samples from si-Pellino1 neonatal rat cardiac myocytes (NRCMs) treated with LPS or left untreated. After normalization of the data, metabolite interaction analysis of matched KEGG pathway associations following si-Pellino1 treatment was applied, accompanied by interaction analysis of gene and metabolite associations after this treatment. Moreover, we used western blot (WB) and polymerase chain reaction (PCR) analyses to determine the expression of genes involved in regulating cardiac energy and energy metabolism in different groups. LC-MS-based metabolic profiling analysis demonstrated that si-Pellino1 treatment could alleviate or even reverse LPS-induced cellular damage by altering cardiomyocytes energy metabolism accompanied by changes in key genes (Cs, Cpt2, and Acadm) and metabolites (3-oxoocotanoyl-CoA, hydroxypyruvic acid, lauroyl-CoA, and NADPH) in NRCMs. Overall, our study unveiled the promising cardioprotective effect of silencing Pellino1 in LPS-induced myocarditis through fuel and energy metabolic regulation, which can also serve as biomarkers for this disease.

Low-intensity pulsed ultrasound prevents prolonged hypoxia-induced cardiac fibrosis through HIF-1α/DNMT3a pathway via a TRAAK-dependent manner.

Hypoxia-induced cardiac fibrosis is an important pathological process in cardiovascular disorders. This study aimed to determine whether low-intensity pulsed ultrasound (LIPUS), a novel and safe apparatus, could alleviate hypoxia-induced cardiac fibrosis, and to elucidate the underlying mechanisms. Hypoxia (1% O2 ) and transverse aortic constriction (TAC) were performed on neonatal rat cardiac fibroblasts and mice to induce cardiac fibrosis, respectively. LIPUS irradiation was applied for 20 minutes every 6 hours for a total of 2 times in vitro, and every 2 days from 1 week before surgery to 4 weeks after surgery in vivo. We found that LIPUS dose-dependently attenuated hypoxia-induced cardiac fibroblast phenotypic conversion in vitro, and ameliorated TAC-induced cardiac fibrosis in vivo. Hypoxia significantly upregulated the nuclear protein expression of hypoxia-inducible factor-1α (HIF-1α) and DNA methyltransferase 3a (DNMT3a). LIPUS pre-treatment reversed the elevated expression of HIF-1α, and DNMT3a. Further experiments revealed that HIF-1α stabilizer dimethyloxalylglycine (DMOG) hindered the anti-fibrotic effect of LIPUS, and hampered LIPUS-mediated downregulation of DNMT3a. DNMT3a small interfering RNA (siRNA) prevented hypoxia-induced cardiac fibrosis. Results also showed that the mechanosensitive protein-TWIK-related arachidonic acid-activated K+ channel (TRAAK) messenger RNA (mRNA) expression was downregulated in hypoxia-induced cardiac fibroblasts, and TAC-induced hearts. TRAAK siRNA impeded LIPUS-mediated anti-fibrotic effect and downregulation of HIF-1α and DNMT3a. Above results indicated that LIPUS could prevent prolonged hypoxia-induced cardiac fibrosis through TRAAK-mediated HIF-1α/DNMT3a signalling pathway.

Celastrol attenuates arterial and valvular calcification via inhibiting BMP2/Smad1/5 signalling.

Vascular calcification is an important risk factor for the mortality and morbidity in chronic kidney disease (CKD). Unfortunately, until now there is no certain medication targeting vascular calcification in CKD. In this study, we explored the inhibitory effect of celastrol on high calcium-induced vascular calcification and the underlying molecular mechanisms. Cell proliferation assay showed that celastrol inhibited aortic valve interstitial cell (VIC) and vascular smooth muscle cell (VSMC) proliferation when its concentration was higher than 0.6 µmol/L. 0.8 µmol/L celastrol inhibited the expression of osteogenic genes and calcium deposition induced by high-calcium medium in both AVICs and VSMCs. In mouse vascular calcification model induced by adenine combined with vitamin D, alizarin red and immunostaining showed that celastrol inhibited pro-calcification gene expression and calcium deposition in aortic wall and aortic valve tissues. At the molecular level, celastrol inhibited the increase of BMP2, phosphorylated Smad1/5 (p-Smad1/5) and non-phosphorylated ß-catenin (n-p-ß-catenin) induced by high-calcium medium both in vitro and in vivo. Also, BMP2 overexpression reversed the anti-calcification effects of celastrol by recovering the decrease of p-Smad1/5 and n-p-ß-catenin. Furthermore, celastrol prevented the up-regulation of BMPRII and down-regulation of Smad6 induced by high calcium, and this protectory effect can be abolished by BMP2 overexpression. In conclusion, our data for the first time demonstrate that celastrol attenuates high calcium-induced arterial and valvular calcification by inhibiting BMP2/Smad1/5 signalling, which may provide a novel therapeutic strategy for arterial and valvular calcification in patients with CKD.

Application of Six Sigma for evaluating the analytical quality of tumor marker assays.

CONTEXT: The results of detection assays for the same specimen are usually quite different in different laboratories or when tested with different detection systems. OBJECTIVE: This study was designed to investigate the value of applying sigma metrics derived from different standards for allowable total error (TEa) in evaluating the analytical quality of tumor marker assays. METHODS: Assays were evaluated for these six tumor markers: total prostate-specific antigen (tPSA), carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), carbohydrate antigen 199 (CA199), carbohydrate antigen 125 (CA125), and carbohydrate antigen 153 (CA153). Sigma values were calculated for two concentrations of quality control products to assess differences in quality of tumor marker assays. Improvement measures were recommended according to the quality goal index, and appropriate quality control rules were selected according to the sigma value. RESULTS: The sigma value was highest using the higher biological variation-derived "appropriate" TEa standard: it was sigma ≥6 or higher in 16.7% of tumor markers. Sigma was below 6 for all tumor markers using the other three TEa. CEA, AFP, CA199, CA125, and CA153 required improved precision. The marker tPSA required improve precision and accuracy. According to sigma values by using China's external quality assessment standards, CEA, AFP, CA125, and CA153 require 13s /22s /R4s /41s multirules for internal quality control, CA199 requires use of 13s /22s /R4s /41s /8x multirules, and tPSA requires maximum quality control rules. CONCLUSION: Six Sigma is useful for evaluating performance of tumor markers assays and has important application value in the quality control of these assays.

Multifunctional paper strip based on GO-veiled Ag nanoparticles with highly SERS sensitive and deliverable properties for high-performance molecular detection.

The development of paper-based SERS substrates that can allow multi-component detection in real-word scenarios is of great value for applications in molecule detection under complex conditions. Here, a multifunctional SERS-based paper sensing substrate has been developed through the uniform patterning of high-density arrays of GO-isolated Ag nanoparticles on the hydrophilic porous cellulose paper strip (GO@AgNP@paper). Wet-chemical synthesis was used to provide the cover of SERS hot spots on any part of the paper, not just limited surface deposition. In virtue of the inherent ability of paper to deliver analytes by the capillary force, the detection ability of the GO@AgNP@paper substrate was greatly promoted, allowing as low as 10-19M R6G detection from microliter-volume (50 µL) samples. For the components with different polarity, the paper substrate can be used as an all-in-one machine to achieve the integration of separation and high-sensitive detection for ultralow mixture components, which improves the practical application value of SERS-based paper devices.

Alamandine attenuates hypertension and cardiac hypertrophy in hypertensive rats.

Oral administration of the peptide alamandine has antihypertensive and anti-fibrotic effects in rats. This work aimed to determine whether subcutaneous alamandine injection would attenuate hypertension and cardiac hypertrophy, and improve the function of a major target of hypertension-related damage, the left ventricle (LV), in spontaneously hypertensive rats (SHRs). This was examined in vivo in SHRs and normotensive rats subjected to 6-week subcutaneous infusion of alamandine or saline control, and in vitro in H9C2-derived and primary neonatal rat cardiomyocytes treated with angiotensin (Ang) II to model cardiac hypertrophy. Tail artery blood pressure measurement and transthoracic echocardiography showed that hypertension and impaired LV function in SHRs were ameliorated upon alamandine infusion. Alamandine administration also decreased the mass gains of heart and lung in SHRs, suppressed cardiomyocyte cross-sectional area expansion, and inhibited the mRNA levels of atrial natriuretic peptide and brain natriuretic peptide. The expression of alamandine receptor Mas-related G protein-coupled receptor, member D was increased in SHR hearts and in cardiomyocytes treated with Ang II. Alamandine inhibited the increases of protein kinase A (PKA) levels in the heart in SHRs and in cardiomyocytes treated with Ang II. In conclusion, the present study showed that alamandine administration attenuates hypertension, alleviates cardiac hypertrophy, and improves LV function. PKA signaling may be involved in the mechanisms underlying these effects.

Novel biomarker pipeline to probe the oxidation sites and oxidation degrees of hemoglobin in bovine erythrocytes exposed to oxidative stress.

Research on biomarkers for protein oxidation might give insight into the mechanistic mode of oxidative stress. In the work present here, a novel pipeline was established to probe the oxidation mechanism of bovine hemoglobin (Hb) with its oxidation products serving as the biomarkers. Reactive oxygen species generated by irradiation were used to mimic oxidative stress conditions to oxidize Hb in bovine erythrocytes. After Hb extraction and digestion, oxidized peptides in the tryptic fragments were assigned by comparison with the extracted ion chromatography spectra of native peptide from the control sample. Subsequent tandem mass spectrometry analysis of these peptides proved that oxidation was limited to partially exposed amino acid residues (α-Phe36 , ß-Met1 , ß-Trp14 , for instance) in Hb. Quantitation analysis on these oxidized peptides showed that oxidation degrees of target sites had positive correlations with the extended oxidation dose and the oxidation processes were also controlled by residues types. Compared with the conventional protein carbonyl assay, the identified oxidized products were feasibility biomarkers for Hb oxidation, indicating that the proposed biomarker pipeline was suitable to provide specific and valid information for protein oxidation. Copyright © 2015 John Wiley & Sons, Ltd.

Synthesis of Calcium(II) Amidinate Precursors for Atomic Layer Deposition through a Redox Reaction between Calcium and Amidines.

We have prepared two new Ca(II) amidinates, which comprise a new class of ALD precursors. The syntheses proceed by a direct reaction between Ca metal and the amidine ligands in the presence of ammonia. Bis(N,N'-diisopropylformamidinato)calcium(II) (1) and bis(N,N'-diisopropylacetamidinato)calcium(II) (2) adopt dimeric structures in solution and in the solid state. X-ray crystallography revealed asymmetry in one of the bridging ligands to afford the structure [(η(2) -L)Ca(µ-η(2) :η(2) -L)(µ-η(2) :η(1) -L)Ca(η(2) -L)]. These amidinate complexes showed unprecedentedly high volatility as compared to the widely employed and commercially available Ca(II) precursor, [Ca3 (tmhd)6 ]. In CaS ALD with 1 and H2 S, the ALD window was approximately two times wider and lower in temperature by about 150 °C than previously reported with [Ca3 (tmhd)6 ] and H2 S. Complexes 1 and 2, with their excellent volatility and thermal stability (up to at least 350 °C), are the first homoleptic Ca(II) amidinates suitable for use as ALD precursors.

Hybrid photon-plasmon nanowire lasers.

Metallic and plasmonic nanolasers have attracted growing interest recently. Plasmonic lasers demonstrated so far operate in hybrid photon-plasmon modes in transverse dimensions, rendering it impossible to separate photonic from plasmonic components. Thus only the far-field photonic component can be measured and utilized directly. But spatially separated plasmon modes are highly desired for applications including high-efficiency coupling of single-photon emitters and ultrasensitivity optical sensing. Here, we report a nanowire (NW) laser that offers subdiffraction-limited beam size and spatially separated plasmon cavity modes. By near-field coupling a high-gain CdSe NW and a 100 nm diameter Ag NW, we demonstrate a hybrid photon-plasmon laser operating at 723 nm wavelength at room temperature, with a plasmon mode area of 0.008λ(2). This device simultaneously provides spatially separated photonic far-field output and highly localized coherent plasmon modes, which may open up new avenues in the fields of integrated nanophotonic circuits, biosensing, and quantum information processing.

Melatonin alleviates high-fat-diet-induced dry eye by regulating macrophage polarization via IFT27 and lowering ERK/JNK phosphorylation.

Dry eye disease is the most common ocular surface disease globally, requiring a more effective treatment. We observed that a high-fat diet induced macrophage polarization to M1 and further induced inflammation in the meibomian and lacrimal glands. A four-week treatment with melatonin (MLT) eye drops can regulate macrophage polarization and alleviate dry eye signs. To investigate the therapeutic effects and mechanisms of action of MLT on high-fat-diet-induced dry eye disease in mice, RAW 264.7 cells pretreated with LPS and/or MLT underwent digital RNA with the perturbation of genes sequencing (DRUG-seq). Results showed that IFT27 was up-regulated, and MAPK pathways were suppressed after MLT pre-treatment. ERK/JNK phosphorylation was reduced in meibomian glands of MLT-treated dry eye mice and increased in IFT27 knockdown RAW 264.7 cells. In summary, MLT regulated macrophage polarization via IFT27 and reduced ERK/JNK phosphorylation. These results support that MLT is a promising medication for dry eye disease.

A 2-decade bibliometric analysis of epigenetics of cardiovascular disease: from past to present.

BACKGROUND: Cardiovascular disease (CVD) remains a major health killer worldwide, and the role of epigenetic regulation in CVD has been widely studied in recent decades. Herein, we perform a bibliometric study to decipher how research topics in this field have evolved during the past 2 decades. RESULTS: Publications on epigenetics in CVD produced during the period 2000-2022 were retrieved from the Web of Science Core Collection (WoSCC). We utilized Bibliometrix to build a science map of the publications and applied VOSviewer and CiteSpace to assess co-authorship, co-citation, co-occurrence, and bibliographic coupling. In total, 27,762 publications were included for bibliometric analysis. The yearly amount of publications experienced exponential growth. The top 3 most influential countries were China, the United States, and Germany, while the most cited institutions were Nanjing Medical University, Harbin Medical University, and Shanghai Jiao Tong University. Four major research trends were identified: (a) epigenetic mechanisms of CVD; (b) epigenetics-based therapies for CVD; (c) epigenetic profiles of specific CVDs; and (d) epigenetic biomarkers for CVD diagnosis/prediction. The latest and most important research topics, including "nlrp3 inflammasome", "myocardial injury", and "reperfusion injury", were determined by detecting citation bursts of co-occurring keywords. The most cited reference was a review of the current knowledge about how miRNAs recognize target genes and modulate their expression and function. CONCLUSIONS: The number and impact of global publications on epigenetics in CVD have expanded rapidly over time. Our findings may provide insights into the epigenetic basis of CVD pathogenesis, diagnosis, and treatment.

Trends in worldwide research on cardiac fibrosis over the period 1989-2022: a bibliometric study.

Background: Cardiac fibrosis is a hallmark of various end-stage cardiovascular diseases (CVDs) and a potent contributor to adverse cardiovascular events. During the past decades, extensive publications on this topic have emerged worldwide, while a bibliometric analysis of the current status and research trends is still lacking. Methods: We retrieved relevant 13,446 articles on cardiac fibrosis published between 1989 and 2022 from the Web of Science Core Collection (WoSCC). Bibliometrix was used for science mapping of the literature, while VOSviewer and CiteSpace were applied to visualize co-authorship, co-citation, co-occurrence, and bibliographic coupling networks. Results: We identified four major research trends: (1) pathophysiological mechanisms; (2) treatment strategies; (3) cardiac fibrosis and related CVDs; (4) early diagnostic methods. The most recent and important research themes such as left ventricular dysfunction, transgenic mice, and matrix metalloproteinase were generated by burst analysis of keywords. The reference with the most citations was a contemporary review summarizing the role of cardiac fibroblasts and fibrogenic molecules in promoting fibrogenesis following myocardial injury. The top 3 most influential countries were the United States, China, and Germany, while the most cited institution was Shanghai Jiao Tong University, followed by Nanjing Medical University and Capital Medical University. Conclusions: The number and impact of global publications on cardiac fibrosis has expanded rapidly over the past 30 years. These results are in favor of paving the way for future research on the pathogenesis, diagnosis, and treatment of cardiac fibrosis.

Age-specific differences in hypertension combination management and associated factors influencing treatment choice.

The current hypertension guideline emphasizes combination therapy, especially single-pill combination therapy (SPC). However, few studies compared the prevalence and factors associated with initial therapy choice across heterogeneous age groups in a current population. First, the authors consecutively identified 964 treatment naïve hypertensive patients in a large academic hospital from 01/31/2019 to 01/31/2020. All patients were grouped into (1) young aged, age < 55; (2) middle-aged, 55≤age < 65; and (3) older aged, age ≥65. The multivariable regression model examined the factors associated with the combination therapy by age group. Overall, 80 (8.3%) were young, 191 (19.8%) were middle, and 693 (71.9%) were older aged. Compared with older age, younger patients were more likely to be male, highly educated, regularly exercised, have metabolic syndrome, and less likely to have cardiovascular-related comorbidities, with a lower systolic but higher diastolic pressure. Only one in five patients used SPC, and the prevalence decreased with age. Besides hypertension grade, young patients without catheterization or echo test were less likely to receive multiple therapies, while older patients who were male with lower weight and lower risk levels were less likely to receive multiple therapies. In conclusion, combination therapy, especially SPC, was underused in the targeted hypertensive population. Our contemporary population study showed that young patients (<55) without a history of catheterization or echo examination and male older-aged (≥65) patients with low-risk classification were the population most likely to be neglected. Such information can help triage medical care resources in improving SPC use.

[Analysis of Change and Driving Factors of River Environmental Quality in China from 2002 to 2020].

According to the river environmental quality, pollutant emission, and investment in environmental pollution control from 2002-2020, the change law and driving factors of river environmental quality in China were evaluated using canonical correlation analysis and the Spearman correlation coefficient to analyze the influence between environmental and pollutant emission/investment in environmental pollution control. The results indicated that the river environmental quality was improved significantly based on the proportion of Class Ⅰ-Ⅲ increasing from 29.1% to 87.4% and the proportion of inferior Class Ⅴ decreasing from 40.9% to 0.2% from 2002-2020. The emission of wastewater and domestic wastewater increased from 4.395×1010 tons and 2.323×1010 tons to 8.491×1010 tons and 6.598×1010 tons, respectively. However, emissions of industrial wastewater decreased from 2.072×1010 tons to 1.680×1010 tons. Investment in environmental pollution control increased from 110.66 billion yuan to 1063.89 billion yuan. The proportion of Class Ⅰ-Ⅲ in seven major river basins, river basins in Zhejiang and Fujian, southwest river basins, and northwest river basins showed a negative correlation for industrial pollutant emissions and a positive correlation for investment in environmental pollution control. The primary measure for the seven major river basins, river basins in Zhejiang and Fujian, and northwest river basins cut down the industrial pollutant emissions, in the order of COD>NH4+-N>total wastewater. The primary measure for southwest river basins increased the investment in environmental pollution control, in the order of industrial investment in environmental pollution control>urban environmental infrastructure construction investment and environmental protection investment in construction projects. These results can provide theoretical and policy suggestions for the improvement of river environmental quality during the "14th Five-Year Plan" period.