Reduction of bitter taste receptor gene family in folivorous colobine primates relative to omnivorous cercopithecine primates.

Bitter taste perception is important in preventing animals from ingesting potentially toxic compounds. Whole-genome assembly (WGA) data have revealed that bitter taste receptor genes (TAS2Rs) comprise a multigene family with dozens of intact and disrupted genes in primates. However, publicly available WGA data are often incomplete, especially for multigene families. In this study, we employed a targeted capture (TC) approach specifically probing TAS2Rs for ten species of cercopithecid primates with diverse diets, including eight omnivorous cercopithecine species and two folivorous colobine species. We designed RNA probes for all TAS2Rs that we modeled to be intact in the common ancestor of cercopithecids ("ancestral-cercopithecid TAS2R gene set"). The TC was followed by short-read and high-depth massive-parallel sequencing. TC retrieved more intact TAS2R genes than found in WGA databases. We confirmed a large number of gene "births" at the common ancestor of cercopithecids and found that the colobine common ancestor and the cercopithecine common ancestor had contrasting trajectories: four gene "deaths" and three gene births, respectively. The number of intact TAS2R genes was markedly reduced in colobines (25-28 detected via TC and 20-26 detected via WGA analysis) as compared with cercopithecines (27-36 via TC and 19-30 via WGA). Birth or death events occurred at almost every phylogenetic-tree branch, making the composition of intact genes variable among species. These results show that evolutionary change in intact TAS2R genes is a complex process, refute a simple general prediction that herbivory favors more TAS2R genes, and have implications for understanding dietary adaptations and the evolution of detoxification abilities.

Heart Failure Post-Myocardial Infarction Promotes Mammary Tumor Growth Through the NGF-TRKA Pathway.

Background: Epidemiological investigations suggest that patients with heart failure have a higher incidence of cancer; however, the causal role of cardiac disease on cancer progression remains unclear. Objectives: This study aimed to investigate the impact and underlying mechanisms of myocardial infarction (MI)-induced heart failure on tumor cell growth. Methods: We generated a syngeneic mouse model by implanting mammary tumor-derived 4T1 cells into BALB/c mice with MI resulting from ligation of the left anterior descending artery. Results: Mice with MI exhibited increased tumor volume, tumor weight, and Ki67-positive proliferative cells in the tumor tissue compared with the sham-operated mice. Furthermore, RNA sequencing analysis in the tumor tissue revealed significant enrichment of pathways related to tumor progression, particularly the PI3K-AKT pathway in the MI mice. Upregulation of tropomyosin receptor kinase A (TRKA) phosphorylation, an upstream regulator of PI3K-AKT signaling, was observed in the tumor tissue of the MI mice. We also observed elevated levels of circulating nerve growth factor (NGF), a ligand of TRKA, and increased NGF expressions in the myocardium after MI. In in vitro experiments, NGF stimulation led to increased cell proliferation, as well as phosphorylation of TRKA and AKT. Notably, inhibition of TRKA by small interfering RNA or the chemical inhibitor GW441756 effectively blocked these effects. Administration of GW441756 resulted in the suppression of tumor volume and cell proliferation in the MI mice. Conclusions: Our study demonstrates that MI promotes mammary tumor growth through the NGF-TRKA pathway. Consequently, inhibiting TRKA could represent a therapeutic strategy for breast cancer patients concurrently experiencing heart failure after MI.

Cigarette Smoking and Atherosclerotic Cardiovascular Disease.

The detrimental effects of cigarette smoking on cardiovascular health, particularly atherosclerosis and thrombosis, are well established, and more detailed mechanisms continue to emerge. As the fundamental pathophysiology of the adverse effects of smoking, endothelial dysfunction, inflammation, and thrombosis are considered to be particularly important. Cigarette smoke induces endothelial dysfunction, leading to impaired vascular dilation and hemostasis regulation. Factors contributing to endothelial dysfunction include reduced bioavailability of nitric oxide, increased levels of superoxide anion, and endothelin release. Chronic inflammation of the vascular wall is a central pathogenesis of smoking-induced atherosclerosis. Smoking systemically elevates inflammatory markers and induces the expression of adhesion molecules and cytokines in various tissues. Pattern recognition receptors and damage-associated molecular patterns play crucial roles in the mechanism underlying smoking-induced inflammation. Smoking-induced DNA damage and activation of innate immunity, such as the NLRP3 inflammasome, cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, and Toll-like receptor 9, are shown to amplify inflammatory cytokine expression. Cigarette smoke-induced oxidative stress and inflammation influence platelet adhesion, aggregation, and coagulation via adhesion molecule upregulation. Furthermore, it affects the coagulation cascade and fibrinolysis balance, causing thrombus formation. Matrix metalloproteinases contribute to plaque vulnerability and atherothrombotic events. The impact of smoking on inflammatory cells and adhesion molecules further intensifies the risk of atherothrombosis. Collectively, exposure to cigarette smoke exerts profound effects on endothelial function, inflammation, and thrombosis, contributing to the development and progression of atherosclerosis and atherothrombotic cardiovascular diseases. Understanding these intricate mechanisms highlights the urgent need for smoking cessation to protect cardiovascular health. This comprehensive review investigates the multifaceted mechanisms through which smoking contributes to these life-threatening conditions.

Predictive Value of Aortic Valve Calcium Volume Measured by Computed Tomography for Paravalvular Leakage After Transcatheter Aortic Valve Implantation.

Paravalvular leakage (PVL) is a complication of transcatheter aortic valve implantation (TAVI) for aortic stenosis, leading to an adverse prognosis. We investigated whether aortic valve calcium volume (Ca-Vol) measured by preoperative cardiac computed tomography had a predictive value for PVL after TAVI using a third-generation self-expandable valve.We retrospectively analyzed 59 consecutive patients who underwent TAVI using a third-generation self-expandable valve. We measured Ca-Vol in the aortic valve and each cusp (non-coronary cusp [NCC], right-coronary cusp [RCC], and left-coronary cusp [LCC]). We divided the patients into 2 groups: a PVL group (32.2%) and a non-PVL group (67.8%). Total Ca-Vol was significantly higher in the PVL group than in the non-PVL group (P < 0.001). Ca-Vol in each cusp was also significantly higher in the PVL group ([NCC] P < 0.001, [RCC] P = 0.001, [LCC] P < 0.001). Univariate logistic regression analysis for PVL indicated that the total and per-cusp Ca-Vols were predictors for PVL (total, odds ratio [OR] 4.0, P < 0.001; NCC, OR 12.5, P = 0.002; RCC, OR 16.0, P = 0.008; LCC, OR 44.5, P < 0.001).Receiver operating characteristic curve analysis of Ca-Vol for predicting PVL revealed the optimal cut-off values of Ca-Vol were 2.4 cm3 for the total, 0.74 cm3 for NCC, 0.73 cm3 for RCC, and 0.56 cm3 for LCC (area under the curve, 0.85, 0.79, 0.76, and 0.83, respectively).Preoperative total, NCC, RCC, and LCC calcium volumes were significant predictors for PVL after TAVI using third-generation self-expandable valves.

Mitochondrial DNA is a key driver in cigarette smoke extract-induced IL-6 expression.

Smoking is an independent risk factor for atherosclerosis, the primary pathogenesis of which is inflammation. We recently reported that cigarette smoke extract (CSE) causes cytosolic and extracellular accumulation of both nuclear (n) and mitochondrial (mt) DNA, which leads to inflammation in human umbilical vein endothelial cells (HUVECs). In this study, we examined whether inflammation induction depends more on cytosolic nDNA or mtDNA, and which chemical constituents of CSE are involved. Acrolein (ACR), methyl vinyl ketone (MVK), and 2-cyclopenten-1-one (CPO) were used in the experiments, as these are the major cytotoxic factors in CSE in various cell types. Stimulation with ACR, MVK, or CPO alone resulted in the accumulation of DNA double-strand breaks (DSBs), but not oxidative DNA damage, accumulation of cytosolic DNA, or increased expression of inflammatory cytokines. Simultaneous administration of all three constituents (ALL) resulted in oxidative DNA damage in both the nucleus and mitochondria, accumulation of DSBs, reduced mitochondrial membrane potential, induction of minority mitochondrial outer membrane permeabilization, accumulation of cytosolic free DNA, and increased expression of inflammatory cytokines such as IL-6 and IL-1α. Treatment with N-acetyl-L-cysteine, a reactive oxygen species scavenger, suppressed oxidative DNA damage and the increased expression of IL-6 and IL-1α induced by ALL or CSE. The ALL- or CSE-induced increase in IL-6 expression, but not that of IL-1α, was suppressed by mtDNA depletion. In conclusion, ACR, MVK, and CPO may strongly contribute to CSE-induced inflammation. More importantly, cytosolic free mtDNA is thought to play an important role in IL-6 expression, a central mediator of inflammation.

Targeting N-Myristoylation Through NMT2 Prevents Cardiac Hypertrophy and Heart Failure.

Protein diversity can increase via N-myristoylation, adding myristic acid to an N-terminal glycine residue. In a murine model of pressure overload, knockdown of cardiac N-myristoyltransferase 2 (NMT2) by adeno-associated virus 9 exacerbated cardiac dysfunction, remodeling, and failure. Click chemistry-based quantitative chemical proteomics identified substrate proteins of N-myristoylation in cardiac myocytes. N-myristoylation of MARCKS regulated angiotensin II-induced cardiac pathological hypertrophy by preventing activations of Ca2+/calmodulin-dependent protein kinase II and histone deacetylase 4 and histone acetylation. Gene transfer of NMT2 to the heart reduced cardiac dysfunction and failure, suggesting targeting N-myristoylation through NMT2 could be a potential therapeutic approach for preventing cardiac remodeling and heart failure.

Viral load of Torquetenovirus correlates with Sano's score and levels of total bilirubin and aspartate aminotransferase in Kawasaki disease.

Cause of Kawasaki disease (KD) is unknown. KD is often resistant to treatment with intravenous immunoglobulin (IVIG). Sano's score, which is derived from total bilirubin (TBIL), aspartate aminotransferase (AST) and C-reactive protein (CRP), is predictive of IVIG resistance in Japan. A recent study reported that Torquetenovirus (TTV), especially TTV7, was present at a high viral load in the patients with KD. We used PCR to quantify TTV load and amplicon next generation sequencing to detect individual TTV species. We used serum samples that were collected between 2002 and 2005 from 57 Japanese KD patients before IVIG treatment. Correlations between TTV load and Sano's score, the biomarkers that constitute this score, and IVIG resistance were examined. TTV load was positively correlated with Sano's score (P = 0.0248), TBIL (P = 0.0004), and AST (P = 0.0385), but not with CRP (P = 0.6178). TTV load was marginally correlated with IVIG resistance (P = 0.1544). Presence of TTV7 was correlated with total TTV load significantly (P = 0.0231). The correlations between biomarkers for KD and TTV load suggested that TTV may play a role in the pathophysiology of KD. We hypothesize that TTV7 may be associated with a higher total viral load in KD.

Acute coronary syndrome with severe coronary calcification in a patient with pseudo-pseudohypoparathyroidism.

A 40-year-old female with a history of steroid therapy for juvenile rheumatoid arthritis was brought to our hospital because of chest pain. A diagnosis of non-ST elevation myocardial infarction was made, and emergency coronary angiography revealed stenotic lesions with severe calcification in the left anterior descending artery and the right coronary artery. Percutaneous coronary intervention with rotational atherectomy followed by a drug-coated balloon was performed to the lesion in the left anterior descending artery. The patient had characteristic physical findings including short stature, a round face, and 'knuckle-dimple sign'. Whole-body computed tomography showed many ectopic calcifications, indicating Albright's hereditary osteodystrophy. Ellsworth-Howard test revealed that urinary cyclic adenosine monophosphate response was positive, thus a diagnosis of pseudo-pseudohypoparathyroidism (PPHP) was made. Here, we describe a rare case of PPHP complicated by acute coronary syndrome with severely calcified coronary arteries. Learning objective: Pseudo-pseudohypoparathyroidism (PPHP) presents with several characteristic physical findings and ectopic calcifications. Since PPHP involves coronary artery calcification as in the present case, it may be considered as a cause of coronary artery disease.

A possible role for proinflammatory activation via cGAS-STING pathway in atherosclerosis induced by accumulation of DNA double-strand breaks.

DNA damage contributes to atherosclerosis. However, causative links between DNA double-strand breaks (DSBs) and atherosclerosis have yet to be established. Here, we investigated the role of DSBs in atherosclerosis using mice and vascular cells deficient in Ku80, a DSB repair protein. After 4 weeks of a high-fat diet, Ku80-deficient apolipoprotein E knockout mice (Ku80+/-ApoE-/-) displayed increased plaque size and DSBs in the aorta compared to those of ApoE-/- control. In the preatherosclerotic stages (two-week high-fat diet), the plaque size was similar in both the Ku80+/-ApoE-/- and ApoE-/- control mice, but the number of DSBs and mRNA levels of inflammatory cytokines such as IL-6 and MCP-1 were significantly increased in the Ku80+/-ApoE-/- aortas. We further investigated molecular links between DSBs and inflammatory responses using vascular smooth muscle cells isolated from Ku80 wild-type and Ku80+/- mice. The Ku80+/- cells displayed senescent features and elevated levels of inflammatory cytokine mRNAs. Moreover, the cytosolic DNA-sensing cGAS-STING pathway was activated in the Ku80+/- cells. Inhibiting the cGAS-STING pathway reduced IL-6 mRNA level. Notably, interferon regulatory factor 3 (IRF3), a downstream effector of the cGAS-STING pathway, was activated, and the depletion of IRF3 also reduced IL-6 mRNA levels in the Ku80+/- cells. Finally, DSBs accumulation in normal cells also activated the cGAS-STING-IRF3 pathway. In addition, cGAS inhibition attenuated DNA damage-induced IL-6 expression and cellular senescence in these cells. These results suggest that DSBs accumulation promoted atherosclerosis by upregulating proinflammatory responses and cellular senescence via the cGAS-STING (-IRF3) pathway.

The Prognostic Implications of Living Alone on Long-Term Mortality in Patients with Chronic Coronary Syndrome after Percutaneous Coronary Intervention.

Living alone is associated with increased cardiac events and mortality in patients with acute myocardial infarction. However, the prognostic impact of living alone with chronic coronary syndrome (CCS) still remains unclear. In the present study, we examined the relationship between living alone and long-term mortality in patients with CCS who underwent percutaneous coronary intervention (PCI).Consecutive 830 patients with CCS who underwent PCI were enrolled and divided into 2 groups according to whether or not they were living alone at the time of admission (living alone group and non-living alone group). We compared the clinical characteristics between the 2 groups and followed up cardiac mortality. The living alone group was younger compared with the non-living alone group (67.5 versus 70.7 years old, P = 0.017). The prevalence of comorbidities, including coronary risk factors, atrial fibrillation, heart failure, stroke, peripheral artery disease, coronary lesion characteristics, laboratory data, and left ventricular ejection fraction, were comparable between the 2 groups. During the follow-up period (median 1,622 days), 52 cardiac deaths occurred. In the Kaplan-Meier analysis, cardiac mortality was significantly higher in the living alone group than in the non-living alone group (24% versus 11%, P = 0.008). In the multivariable Cox proportional hazard analyses after adjusting for possible confounding factors, living alone was an independent predictor of cardiac mortality (hazard ratio, 2.426, 95% confidence interval 1.225-4.804, P = 0.011).Among CCS patients who underwent PCI, living alone was associated with high long-term cardiac mortality.

Identification of Torquetenovirus Species in Patients with Kawasaki Disease Using a Newly Developed Species-Specific PCR Method.

A next-generation sequencing (NGS) study identified a very high viral load of Torquetenovirus (TTV) in KD patients. We aimed to evaluate the feasibility of a newly developed quantitative species-specific TTV-PCR (ssTTV-PCR) method to identify the etiology of KD. We applied ssTTV-PCR to samples collected from 11 KD patients and 22 matched control subjects who participated in our previous prospective study. We used the NGS dataset from the previous study to validate ssTTV-PCR. The TTV loads in whole blood and nasopharyngeal aspirates correlated highly (Spearman's R = 0.8931, p < 0.0001, n = 33), supporting the validity of ssTTV-PCR. The ssTTV-PCR and NGS results were largely consistent. However, inconsistencies occurred when ssTTV-PCR was more sensitive than NGS, when the PCR primer sequences mismatched the viral sequences in the participants, and when the NGS quality score was low. Interpretation of NGS requires complex procedures. ssTTV-PCR is more sensitive than NGS but may fail to detect a fast-evolving TTV species. It would be prudent to update primer sets using NGS data. With this precaution, ssTTV-PCR can be used reliably in a future large-scale etiological study for KD.

Impact of bleeding event for new cancer diagnosis in patients with antiplatelet therapy after percutaneous coronary intervention.

BACKGROUND: Bleeding is a frequent event in coronary artery disease (CAD) patients treated with antiplatelet therapy after percutaneous coronary intervention (PCI). The impact of bleeding in CAD patients with antiplatelet therapy for cancer diagnosis remains unclear. METHODS AND RESULTS: Consecutive 1565 CAD patients treated with antiplatelet therapy after PCI, without anticoagulation therapy, were enrolled. We aimed to investigate the relationships between bleeding events and the incidence of new cancer diagnosis. Among 1565 patients, 178 (11.3 %) experienced any bleeding events defined as Bleeding Academic Research Consortium (BARC) type 1, 2, 3, or 5 bleeding and 75 (4.7 %) experienced minor bleeding events defined as BARC 1 or 2 bleeding, and 116 (7.4 %) were diagnosed with new cancer during a mean follow-up period of 1528 days. Among 178 patients with any bleeding and 75 patients with minor bleeding events, 20 (11.2 %) and 13 (17.3 %) were subsequently diagnosed with new cancer, respectively. The proportion of new cancer diagnosis was higher in patients with any bleeding and minor bleeding events than in those without bleeding events (3.3 versus 1.6 per 100 person-years, p < 0.001 and 6.2 versus 1.6 per 100 person-years, p < 0.001, respectively). Multivariate Cox proportional hazard analysis revealed that any bleeding and minor bleeding events were associated with higher rate of new cancer diagnosis [hazard ratio (HR) 2.27, p = 0.003 and HR 3.93, p < 0.001, respectively]. Additionally, any gastrointestinal bleeding and minor gastrointestinal bleeding events were associated with higher rate of new gastrointestinal cancer diagnosis (HR 8.67, p < 0.001 and HR 12.74, p < 0.001, respectively). CONCLUSIONS: In CAD patients with antiplatelet therapy after PCI, any bleeding and minor bleeding events were associated with subsequent new cancer diagnosis. Even minor bleeding events may be the first manifestation of underlying cancer during antiplatelet therapy after PCI.

Carbonization of a Molybdenum Substrate Surface and Nanoparticles by a One-Step Method of Femtosecond Laser Ablation in a Hexane Solution.

Molybdenum carbides (MoC and Mo2C) are being reported for various applications, for example, catalysts for sustainable energies, nonlinear materials for laser applications, protective coatings for improving tribological performance, and so on. A one-step method for simultaneously fabricating molybdenum monocarbide (MoC) nanoparticles (NPs) and MoC surfaces with a laser-induced periodic surface structure (LIPSS) was developed by using pulsed laser ablation of a molybdenum (Mo) substrate in hexane. Spherical NPs with an average diameter of 61 nm were observed by scanning electron microscopy. The X-ray diffraction pattern and electron diffraction (ED) pattern results indicate that a face-centered cubic MoC was successfully synthesized for the NPs and on the laser-irradiated area. Notably, the ED pattern suggests that the observed NPs are nanosized single crystals, and a carbon shell was observed on the surface of MoC NPs. The X-ray diffraction pattern of both MoC NPs and LIPSS surface indicates the formation of FCC MoC, agreeing with the results of ED. The results of X-ray photoelectron spectroscopy also showed the bonding energy attributed to Mo-C, and the sp2-sp3 transition was confirmed on the LIPSS surface. The results of Raman spectroscopy have also supported the formation of MoC and amorphous carbon structures. This simple synthesis method for MoC may provide new possibilities for preparing Mo x C-based devices and nanomaterials, which may contribute to the development of catalytic, photonic, and tribological fields.

A case of COVID-19-associated fulminant myocarditis due to SARS-CoV-2 omicron BA.2 sub-lineage in an unvaccinated female.

COVID-19-associated myocarditis can be a lethal complication in previous variants, but it is not well understood in the Omicron variant. We present an unvaccinated case of COVID-19-associated fulminant myocarditis due to the Omicron BA.2 sub-lineage requiring mechanical circulatory support (MCS). A 66-year-old female without vaccination against SARS-CoV-2 was hospitalized due to COVID-19. On the next day, she was transferred to our hospital due to the development of fulminant myocarditis. After arrival, she was treated with Impella CP and venoarterial extracorporeal membrane oxygenation due to unstable hemodynamics. In addition to MCS, we treated her with inotropes, methylprednisolone, tocilizumab, and remdesivir. Left ventricular contraction gradually improved, and MCS was removed on day 8. Endomyocardial biopsy showed mild interstitial infiltration of CD3+-T lymphocytes and CD68+-macrophages with no remarkable necrosis or fibrosis. This case showed similar histological characteristics to COVID-19-associated myocarditis before the Omicron variant. The vaccination against the Omicron variant should be considered to prevent the development of severe illness, including fulminant myocarditis. Learning objective: Although the Omicron variant is thought to be generally less severe, COVID-19-associated fulminant myocarditis, as in this case, can occur. The vaccination against the Omicron variant should be considered to prevent from developing severe illness.

A rare case of fibromuscular dysplasia with multifocal coronary artery involvement evaluated by intravascular ultrasound.

Fibromuscular dysplasia (FMD) is non-atherosclerotic, non-inflammatory vascular disease that results in arterial stenosis. The lesions in FMD are commonly found in the renal and extracranial carotid and vertebral arteries, but the prevalence of FMD with lesions in the coronary artery is unclear. Although the vascular morphology of coronary artery lesion in FMD is mostly dissection, the following case of FMD showed the stenotic and aneurysmal lesions in coronary arteries, which was treated by percutaneous coronary angioplasty. Several vascular imaging modalities including computed tomographic angiography and catheter angiography are used for diagnosing FMD, however, the intravascular ultrasound (IVUS) imaging of the coronary artery in FMD has not been well studied. Here we describe a rare case of FMD involving multifocal coronary artery lesions with coronary aneurysm which was evaluated by IVUS imaging. Learning objective: The vascular morphologies of coronary artery lesion in fibromuscular dysplasia (FMD) mostly appear as coronary dissection, however, multifocal stenotic and aneurysmal lesions can occur in coronary arteries in FMD as the following case shows. The intravascular ultrasound findings of the stenotic coronary lesions in FMD, that were circumferential thickening of intima with various echo patterns and echolucent circumferential thickened media, may help in the diagnosis of FMD involving coronary arteries.

Cigarette smoke induces mitochondrial DNA damage and activates cGAS-STING pathway: application to a biomarker for atherosclerosis.

Cigarette smoking is a major risk factor for atherosclerosis. We previously reported that DNA damage was accumulated in atherosclerotic plaque, and was increased in human mononuclear cells by smoking. As vascular endothelial cells are known to modulate inflammation, we investigated the mechanism by which smoking activates innate immunity in endothelial cells focusing on DNA damage. Furthermore, we sought to characterize the plasma level of cell-free DNA (cfDNA), a result of mitochondrial and/or genomic DNA damage, as a biomarker for atherosclerosis. Cigarette smoke extract (CSE) increased DNA damage in the nucleus and mitochondria in human endothelial cells. Mitochondrial damage induced minority mitochondrial outer membrane permeabilization, which was insufficient for cell death but instead led to nuclear DNA damage. DNA fragments, derived from the nucleus and mitochondria, were accumulated in the cytosol, and caused a persistent increase in IL-6 mRNA expression via the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. cfDNA, quantified with quantitative PCR in culture medium was increased by CSE. Consistent with in vitro results, plasma mitochondrial cfDNA (mt-cfDNA) and nuclear cfDNA (n-cfDNA) were increased in young healthy smokers compared with age-matched nonsmokers. Additionally, both mt-cfDNA and n-cfDNA were significantly increased in patients with atherosclerosis compared with the normal controls. Our multivariate analysis revealed that only mt-cfDNA predicted the risk of atherosclerosis. In conclusion, accumulated cytosolic DNA caused by cigarette smoke and the resultant activation of the cGAS-STING pathway may be a mechanism of atherosclerosis development. The plasma level of mt-cfDNA, possibly as a result of DNA damage, may be a useful biomarker for atherosclerosis.

Static Hydrophobic Cuprous Oxide Surface Fabricated via One-Step Laser-Induced Oxidation of a Copper Substrate.

In this study, we developed a one-step method for fabricating hydrophobic surfaces on copper (Cu) substrates. Cuprous oxide (Cu2O) with low free energy was successfully formed after low-fluence laser direct irradiation. The formation of Cu2O enhanced the hydrophobicity of the Cu substrate surface, and the contact angle linearly increased with the proportion of Cu2O. The Cu2O fabricated by low-fluence laser treatment showed the same crystal plane orientation as the pristine Cu substrate, implying an epitaxial growth of Cu2O on a Cu substrate.

Cancer therapeutics-related cardiovascular dysfunction: Basic mechanisms and clinical manifestation.

Although recent advances in cancer treatment improve cancer prognosis, cancer therapeutics-related cardiovascular dysfunction (CTRCD) significantly contributes to the global burden of cardiovascular disease. CTRCD causes two crucial issues: first, premature treatment interruption or discontinuation of chemotherapy; second, the development of congestive heart failure during and after cancer treatment. Thus, early detection and prompt treatment of CTRCD may improve the prognosis in cancer patients. This review covers representative anticancer drugs, including anthracyclines, human epidermal growth factor 2 inhibitors, tyrosine kinase inhibitors, proteasome inhibitors, and immune checkpoint inhibitors. We focus on the molecular mechanisms of CTRCD and various approaches to diagnosis, prevention, monitoring, and treatment.

Role of DNA damage in the pathogenesis of atherosclerosis.

Atherosclerosis is a cause of coronary artery disease, abdominal aortic aneurysm, and stroke. The pathogenesis underlying atherosclerosis is complex but it is clear that inflammation plays a pivotal role. Inflammation in atherosclerosis is triggered by the recognition of intracellular contents released from damaged cells by pattern recognition receptors, and is therefore sterile and chronic. Because the DNA of these cells is damaged, cellular senescence is also involved in this inflammation. Here, we will discuss the emerging evidence of a relationship between DNA damage and inflammation in the pathogenesis of atherosclerosis, with a focus on intracellular events and cell fates that arise following DNA damage. Recent evidence will lead us to potential therapeutic targets and allow us to explore potential preventative and therapeutic strategies.

The Prognostic Impact of D-Dimer on Long-Term Mortality in Patients with Coronary Artery Disease after Percutaneous Coronary Intervention.

D-dimer is a common measurable coagulation marker that is associated with the risk of thrombotic events in vascular diseases. However, the impact of D-dimer on long-term mortality in coronary artery disease (CAD) patients remains unclear. This study investigated the association between D-dimer and long-term all-cause, cardiac and cancer mortality in CAD patients. Continuous 1,440 patients with CAD who underwent percutaneous coronary intervention (PCI) and survived to discharge were enrolled. These patients were divided into 3 groups based on plasma D-dimer levels at admission. Baseline D-dimer levels were grouped by tertiles: first (D-dimer < 0.7 µg/mL, n = 455), second (0.7 ≤ D-dimer < 1.2, n = 453), and third (1.2 ≤ D-dimer, n = 532). In a Kaplan-Meier analysis (mean follow-up periods 1,572 days), all-cause, cardiac and cancer mortalities were significantly higher in the third tertile than others (P < 0.001, P < 0.001 and P < 0.001, respectively). In multivariable Cox proportional hazard analyses after adjusting for confounding factors, a high D-dimer level was an independent predictor of all-cause, cardiac, non-cardiac and cancer mortalities (HR 3.23, P < 0.001; HR 3.06, P = 0.008; HR 3.11, P = 0.026). In a subgroup analysis, there were no interactions except for the gender subgroup in cancer mortality. In patients with CAD after PCI, high D-dimer levels were associated with long-term all-cause, cardiac and cancer mortality.