Indobufen or Aspirin on Top of Clopidogrel After Coronary Drug-Eluting Stent Implantation (OPTION): A Randomized, Open-Label, End Point-Blinded, Noninferiority Trial.

BACKGROUND: Dual antiplatelet therapy (DAPT) with aspirin as a background therapy has become the standard care after percutaneous coronary intervention. However, some adverse noncardiac effects limited the use of aspirin in clinical practice. Thus, evaluation of pharmacological alternatives to aspirin is attractive. Previous data indicated that indobufen could lessen the unwanted side effects of aspirin while retaining the antithrombotic efficacy, but its combination with a P2Y12 inhibitor still lacks randomized clinical trial evidence. METHODS: In this randomized, open-label, noninferiority trial, patients with negative cardiac troponin undergoing coronary drug-eluting stent implantation were randomly assigned in a 1:1 ratio to receive either indobufen-based DAPT (indobufen 100 mg twice a day plus clopidogrel 75 mg/d for 12 months) or conventional DAPT (aspirin 100 mg/d plus clopidogrel 75 mg/d for 12 months). The primary end point was a 1-year composite of cardiovascular death, nonfatal myocardial infarction, ischemic stroke, definite or probable stent thrombosis, or Bleeding Academic Research Consortium criteria type 2, 3, or 5 bleeding. The end points were adjudicated by an independent Clinical Event Committee. RESULTS: Between January 11, 2018, and October 12, 2020, 4551 patients were randomized in 103 cardiovascular centers: 2258 patients to the indobufen-based DAPT group and 2293 to the conventional DAPT group. The primary end point occurred in 101 patients (4.47%) in the indobufen-based DAPT group and 140 patients (6.11%) in the conventional DAPT group (absolute difference, -1.63%; Pnoninferiority<0.001; hazard ratio, 0.73 [95% CI, 0.56-0.94]; P=0.015). Cardiovascular death, nonfatal myocardial infarction, ischemic stroke, and stent thrombosis were observed in 0.13%, 0.40%, 0.80%, and 0.22% of patients in the indobufen-based DAPT group and 0.17%, 0.44%, 0.83%, and 0.17% of patients in the conventional DAPT group (all P>0.05). The occurrence of Bleeding Academic Research Consortium criteria type 2, 3, or 5 bleeding events was lower in the indobufen-based DAPT group compared with the conventional DAPT group (2.97% versus 4.71%; hazard ratio, 0.63 [95% CI, 0.46-0.85]; P=0.002), with the main decrease in type 2 bleeding (1.68% versus 3.49%; hazard ratio, 0.48 [95% CI, 0.33-0.70]; P<0.001). CONCLUSIONS: In Chinese patients with negative cardiac troponin undergoing drug-eluting stent implantation, indobufen plus clopidogrel DAPT compared with aspirin plus clopidogrel DAPT significantly reduced the risk of 1-year net clinical outcomes, which was driven mainly by a reduction in bleeding events without an increase in ischemic events. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR-IIR-17013505.

Triglyceride-glucose index is associated with severe obstructive coronary artery disease and atherosclerotic target lesion failure among young adults.

BACKGROUND: Early diagnosis and treatment effectiveness of early-onset coronary artery disease (EOCAD) are crucial, and non-invasive predictive biomarkers are needed for young adults. We aimed to evaluate the usefulness of the triglyceride-glucose (TyG) index, a novel marker of insulin resistance, in identifying young CAD patients and predicting their risk of developing target lesion failure (TLF). METHODS: We recruited EOCAD patients (luminal narrowing ≥ 70%) and controls free from CAD (luminal narrowing < 30%), both aged 45 years or younger, from 38 hospitals in China between 2017 and 2020. EOCAD patients who underwent successful percutaneous coronary intervention were followed for incident TLF. TyG index was defined as Ln [fasting triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2]. We used logistic regression and Cox proportional hazards modeling to evaluate the association of TyG index with prevalent EOCAD and incident TLF, respectively. The discriminatory ability of TyG index was assessed by the area under the receiver-operating characteristic curve (AUC). RESULTS: Among the included 1513 EOCAD patients (39.6 ± 4.4 years, 95.4% male) and 1513 age-matched controls (39.0 ± 4.4 years, 46.4% male), TyG index was positively associated with the prevalence of EOCAD (adjusted odds ratio: 1.40, 95% confidence interval [CI] 1.23-1.60, per standard deviation [SD] increase in TyG index). The addition of TyG index to an empirical risk model provided an improvement in diagnostic ability for EOCAD, with a net reclassification improvement of 0.10 (95% CI 0.03-0.17, p = 0.005). During a medium of 33 month (IQR: 31-34 months) follow-up, 43 (3.3%) patients experienced TLF. Multivariate Cox regression model revealed that TyG index was an independent risk factor for TLF (adjusted hazard ratio [HR]: 2.410, 95% CI 1.07-5.42 comparing the top to bottom TyG index tertile groups; HR: 1.30, 95% CI 1.01-1.73, per SD increase in TyG index). Compared with a model of conventional risk factors alone, the addition of the TyG index modestly improved the AUC (0.722-0.734, p = 0.04) to predict TLF. CONCLUSIONS: TyG index is positively associated with prevalent EOCAD and incident TLF. TyG index appeared to be a valuable component of future efforts to improve CAD risk stratification and TLF outcome prediction among young adults.

How does bivalve size influence microplastics accumulation?

Microplastics (wasted plastic particles < 5 mm in diameter) are ubiquitously distributed in the marine environment. Filter-feeding and low trophic level bivalves are vulnerable to microplastics accumulation from the surrounding depositional environment, thereby threatening both ecological health and human food safety. Microplastics had been detected in lots of coastal Bivalvia species. However, the influence of biological morphology on the mechanism of microplastics accumulation is not clear. There is also a knowledge gap of which species are preferred for commercial consumption, which creates loopholes in risk identification for food safety. A survey on a commercial popular eaten but under-researched hard clam (Meretrix meretrix; Linnaeus, 1758) from a famous fishery port city in southern China was carried out to comprehensively analyze shell size influence on microplastics accumulation in bivalves and consequently, human intake risk via bivalve consumption. Detected microplastics count in per individual (MCI) was 24.64 ± 19.11 items · individual-1, and microplastics count per gram (MCG; wet weight with shell) was 0.66 ± 0.54 items · g-1. When the shell width grew by 1 mm, MCI increased by 1.01 times, but MCG decreased by 0.97 times. Dominant microplastics characteristics found in this study was fiber and fragment. Sizes ranged from 25 to 150 µm, and dark colors (black, red, and blue) were found. The mostly common polymers were polyethene (PE, 40%), polyethylene terephthalate (PET, 23%), and polypropylene (PP, 18%). Estimated annual intake (EAI) risk of microplastics via hard clam consumption by residents was 6652.26 ± 5327.28 items · year -1 · person -1. The microplastics in bivalves and EAI was relatively high. When shell width grew by 1 mm, EAI decreased by 0.97 times. Therefore, eating a fixed amount of larger hard clams with a relatively low amount of microplastics can reduce EAI risk for consumers. A systematic investigation of emission sources along main coast, where bivalve production is prominent will be useful for food safety control in this region.

Mechanisms of Myocardial Damage Due to Hyperlipidemia: A Review of Recent Studies.

Myocardial injury and necrosis caused by hyperlipidemia have been investigated by several researchers. Their pathogenesis and molecular basis are different from those of the more common clinical ischemic myocardial injury. Hyperlipidemia leads to peroxide accumulation in the cardiomyocytes, causes lipid overload, decreases the antioxidant capacity of the body, and promotes the inflammatory response. Furthermore, hyperlipidemia causes changes in the structure and function of mitochondria in the cardiomyocytes, which results in their injury and necrosis. Many previous studies have shown that metabolic diseases (eg, obesity and diabetes) and chemical poisoning can lead to hyperlipidemic myocardial injury and necrosis. Moreover, it has been observed that this pathological process can be inhibited by many small molecular substances. In the clinic, myocardial damage can be prevented or reduced by lowering the levels of triglyceride and cholesterol. Myocardial damage can also be regulated via the molecular pathway of myocardial injury caused by hyperlipidemia so that the disease can be treated. The present article reviewed the recent findings reported on the mechanisms of myocardial damage due to hyperlipidemia.

Cilostazol increases adenosine plasma concentration in patients with acute coronary syndrome.

WHAT IS KNOWN AND OBJECTIVE: Cilostazol is a specific and strong inhibitor of phosphodiesterase (PDE) type III which can suppress the platelet aggregation by increasing cyclic adenosine monophosphate (cAMP) levels. The clinical benefit of cilostazol in ACS patients suggested that the drug may have non-platelet-directed properties. Some in vitro and animal studies also indicated that the 'pleiotropic' properties of cilostazol might be related to the interaction with adenosine metabolism. Adenosine is an important regulatory metabolite and an inhibitor of platelet activation. However, no human study has been conducted to determine whether cilostazol could increase the adenosine plasma concentration in vivo. As a result, this study aimed to investigate the impact of cilostazol on adenosine plasma concentration (APC) in acute coronary syndrome (ACS) patients. METHODS: We prospectively analysed 149 ACS patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents. The included patients were divided into two groups according to the presence (cilostazol group, n = 64) or absence (aspirin group, n = 85) of aspirin intolerance. The inhibition of platelet aggregation (IPA), APC and cAMP concentration was measured. Patient characteristics, medications and 30-day clinical outcomes were examined. RESULTS: Patients receiving cilostazol had a significantly higher adenosine and cAMP plasma concentration than patients receiving aspirin (3.00 ± 0.67 vs 2.56 ± 0.74 mol/L, P < .001; 28.10 ± 14.74 vs 20.48 ± 11.35 pmol/mL, P = .0014). Cilostazol was associated with a higher inhibition rate of ADP induced platelet aggregation than aspirin (63.35 ± 26.71 vs 52.2 ± 28.35, P = .036). The plasma levels of adenosine and cAMP showed a positive correlation with ADP induced platelet aggregation. WHAT IS NEW AND CONCLUSION: Cilostazol increases adenosine concentration compared with aspirin. Its potent antiplatelet effect in ACS patients may be partly mediated by adenosine.

User Local Coordinate-Based Accompanying Robot for Human Natural Movement of Daily Life.

Considering the trend of aging societies, accompanying technology can help frail, elderly individuals participate in daily activities. The ideal accompanying robot should accompany the user in a proper position according to the activity scenarios and context; the prerequisite is that the accompanying robot should quickly move to a designated position and closely maintain it regardless of the direction in which the user moves. This paper proposes a user local coordinate-based strategy to satisfy this need. As a proof of concept, a novel "string-pot" approach was utilized to measure the position difference between the robot and the target. We implemented the control strategy and assessed its performance in our gait lab. The results showed that the robot can follow the user in the designated position while the user performs forward, backward, and lateral movements, turning, and walking along a curve.

Residual platelet reactivity is preferred over platelet inhibition rate in monitoring antiplatelet efficacy: insights using thrombelastography.

Although thrombelastography (TEG) has been widely implemented in the clinical setting of endovascular intervention, consensus on the optimal parameter for defining high ischemic risk patients is lacking due to the limited data about the relationship between various TEG parameters and clinical outcomes. In this article, we report a post hoc analysis of a prospective, single-center cohort study, including 447 patients with acute coronary syndrome (ACS). Arachidonic acid (AA)- or adenosine diphosphate (ADP)-induced platelet-fibrin clot strength (MAAA or MAADP) was indicative of the net residual platelet reactivity after the treatment with aspirin or clopidogrel, respectively. AA% or ADP% was indices of the relative platelet inhibition rate on AA or ADP pathway. We found that each parameter alone was predictive of the risk of 6-month ischemic event, even after adjusting for confounding factors. However, the association between AA% and clinical outcome disappeared when further adjusted for MAAA. Likewise, inclusion of MAADP changed the significant relation between ADP% and clinical outcome. MAADP > 47.0 mm and MAAA > 15.1 mm were identified as the optimal cutoffs by receiver operating characteristic analysis. High MAAA (HR = 3.963; 95% CI: 1.152-13.632; P = 0.029) and high MAADP (HR = 5.185; 95% CI: 2.228-12.062; P < 0.001) were independent predictors when both were included in multivariable Cox regression hazards model. Interestingly, an even higher risk was found for the coexisting high MAAA and high MAADP (HR = 7.870; 95% CI: 3.462-17.899; P < 0.001). We conclude that when performing TEG to predict clinical efficacy, residual platelet reactivity has superiority over platelet inhibition rate as a measure of thrombotic risk in patients treated with aspirin and clopidogrel after ACS.

Prognostic value of systemic inflammatory factors NLR, LMR, PLR and LDH in penile cancer.

BACKGROUND: Penile squamous cell carcinoma (PSCC) represents an important public health problem for developing countries. The major prognostic factors in PSCC are pathological subtype, perineural invasion, lymphovascular invasion, depth of invasion and grade, which are hard to obtain precisely before the operation. Besides, micro-metastases will be detected in about 30% of intermediate-risk patients with clinically non-palpable inguinal lymph nodes after inguinal lymph node dissection (ILND). It means approximately 70% of patients are unable to benefit from ILND who might suffered from the complications of surgery. We hope some biomarkers could be found which are able to predict the outcome before surgery and reflect the inguinal lymph nodes metastasis. METHODS: A total of 349 consecutive patients of penile cancer in Yunnan cancer hospital in China between October 2002 and December2017. Two hundred twenty-five was succeed to follow-up. The association between NLR, LMR, PLR, LDH and Overall survival (OS), progression free survival (PFS), inguinal lymph node (N stage) was analyzed with K-M analysis, univariable, multivariable logistic regression and Kendall's tau-b correlation coefficient. RESULTS: Multivariable analysis reveal that only PLR was significant independent factor which is associated with inferior OS and PFS; Age and LDH was associated with inferior OS; Lymph node and metastatic status remained significant for OS and PFS as NCCN and EAU Guidelines indicated; the tumor type, initial treatment and NLR LMR were not significant in predicting both OS and PFS. NLR, LMR and PLR were corresponded to N stage, while LDH was not associated with the N stage based on logistic regression model analysis. NLR, LMR and PLR were found weakly related to N stage through an application of Kendall's tau-b correlation coefficient. CONCLUSIONS: PLR was significant independent factors for OS and PFS, Age and LDH was significant independent factors for OS. NLR, LMR, PLR was corresponded to N stage.

Efficacy assessment of ticagrelor versus clopidogrel in Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention by data mining and machine-learning decision tree approaches.

WHAT IS KNOWN AND OBJECTIVE: Although ticagrelor has been well-known to improve clinical outcomes in patients undergoing percutaneous coronary intervention (PCI), and its effectiveness and safety have not been well evaluated in Chinese patients. This study aimed to evaluate the effectiveness and safety of ticagrelor in Chinese patients. In order to find potential effect modifiers on the drug effects, a decision tree method was performed to detect interactions between treatment and patient characteristics in an automatic and systematic manner. METHODS: This retrospective study included acute coronary syndrome (ACS) patients who underwent PCI and received either ticagrelor (N = 250) or clopidogrel (N = 291) while hospitalized between August 2014 and August 2015. After propensity score matching, Kaplan-Meier analysis was used to study the event-free survival against major adverse cardiovascular events (MACE, primary efficacy outcome, defined as the composite of cardiac death, non-fatal myocardial infarction [MI], stroke, restenosis and target vessel revascularization [TVR]), re-hospitalization, the need for urgent re-PCI (secondary efficacy outcome) and bleeding events (safety outcome) within 12 months of the PCI date. To search for effect modifiers of the two antiplatelet therapies, a machine-learning decision tree algorithm was conducted to predict re-hospitalization status. RESULTS: After propensity score matching (N = 442), ticagrelor and clopidogrel had no significant difference in MACE, re-hospitalization and bleeding. The decision tree analysis showed that the number of diseased vessels modulated the effect of ticagrelor and clopidogrel on re-hospitalization rates. In single-vessel disease (SVD) patients, ticagrelor was associated with lower hazards than clopidogrel for all efficacy outcomes: MACE (HR = 0.190, 95% CI: 0.042-0.866), re-hospitalization (HR = 0.296, 95% CI: 0.108-0.808), urgent re-PCI (HR = 0.249, 95% CI: 0.069-0.895), bleeding (HR = 1.006, 95% CI: 0.063-16.129). However, in multi-vessel disease (MVD) patients, the two treatments did not show significant difference. WHAT IS NEW AND CONCLUSION: In the general patient population, there was no significant difference between ticagrelor and clopidogrel on the hazard of MACE. However, ticagrelor achieved a better effectiveness than clopidogrel in patients with SVD. This pilot study provides scientific basis to call for a large-scale prospective study in this population.

Antithrombotic Therapy of a Young Adult with Giant Left Main Coronary Artery Aneurysm.

Giant coronary artery aneurysm (CAA) is a rare disorder, defined as coronary artery dilatation, in which the diameter of the coronary artery exceeds more than 1.5 times of its normal size. The most common cause of CAA is coronary atherosclerosis for adults and Kawasaki disease (KD) for children and adolescents (especially for the giant CAA that occurred in adolescence). CAA complications include thrombus, acute myocardial infarction (AMI), vasospasm, rupture, ischemia, heart failure, and arrhythmia. So, antithrombotic therapy is crucial for patients with giant CAA.Although giant CAA has been reported in some cases before, few of these cases described antithrombotic therapy particularly, let alone informed direct oral anticoagulant (DOAC) use in these patients. Here, we report a case of a young patient with acute coronary artery disease caused by huge CAA. Rivaroxaban combined with clopidogrel was used for his antithrombotic therapy. Moreover, we reviewed the existing reports to provide an overview of antithrombotic treatment in patients with giant CAA.

The efficacy and safety of cilostazol as an alternative to aspirin in Chinese patients with aspirin intolerance after coronary stent implantation: a combined clinical study and computational system pharmacology analysis.

Dual antiplatelet therapy (DAT) with aspirin and clopidogrel is the standard regimen to achieve rapid platelet inhibition and prevent thrombotic events. Currently, little information is available regarding alternative antiplatelet therapy in patients with an allergy or intolerance to aspirin. Although cilostazol is already a common alternative to aspirin in clinical practice in China, its efficacy and safety remain to be determined. We retrospectively analyzed 613 Chinese patients who had undergone primary percutaneous coronary intervention (PCI). Among them, 405 patients received standard DAT (aspirin plus clopidogrel) and 205 patients were identified with intolerance to aspirin and received alternative DAT (cilostazol plus clopidogrel). There were no significant differences between the two groups in their baseline clinical characteristics. The main outcomes of the study included major adverse cardiac events (MACEs) and bleeding events during 12 months of follow-up. The MACEs endpoint was reached in 10 of 205 patients treated with cilostazol (4.9%) and in 34 of 408 patients treated with aspirin (8.3%). No statistically significant difference was observed in MACEs between the two groups. However, patients in the cilostazol group had less restenosis than did patients in the aspirin group (1.5% vs 4.9%, P=0.035). The occurrence of bleeding events tended to be lower in the cilostazol group (0.49% vs 2.7%, P=0.063). These clinical observations were further analyzed using network system pharmacology analysis, and the outcomes were consistent with clinical observations and preclinical data reports. We conclude that in Chinese patients with aspirin intolerance undergoing coronary stent implantation, the combination of clopidogrel with cilostazol may be an efficacious and safe alternative to the standard DAT regimen.

Multiple systemic embolism in infective endocarditis underlying in Barlow's disease.

BACKGROUND: Systemic embolism, especially septic embolism, is a severe complication of infective endocarditis (IE). However, concurrent embolism to the brain, coronary arteries, and spleen is very rare. Because of the risk of hemorrhage or visceral rupture, anticoagulants are recommended only if an indication is present, e.g. prosthetic valve. Antiplatelet therapy in IE is controversial, but theoretically, this therapy has the potential to prevent and treat thrombosis and embolism in IE. Unfortunately, clinical trial results have been inconclusive. CASE PRESENTATION: We describe a previously healthy 50-year-old man who presented with dysarthria secondary to bacterial endocarditis with multiple cerebral, coronary, splenic, and peripheral emboli; antibiotic therapy contributed to the multiple emboli. Emergency splenectomy was performed, with subsequent mitral valve repair. Pathological examination confirmed mucoid degeneration and mitral valve prolapse (Barlow's disease) as the underlying etiology of the endocardial lesion. Continuous antibiotics were prescribed, postoperatively. Transthoracic echocardiography at 1.5, 3, and 6 months after the onset of his illness showed no severe regurgitation, and there was no respiratory distress, fever, or lethargy during follow-up. CONCLUSIONS: Although antibiotic use in IE carries a risk of septic embolism, these drugs have bactericidal and antithrombotic benefits. It is important to consider that negative blood culture and symptom resolution do not confirm complete elimination of bacteria. However, vegetation size and Staphylococcus aureus infection accurately predict embolization. It is also important to consider that bacteria can be segregated from the microbicide when embedded in platelets and fibrin. Therefore, antimicrobial therapy with concurrent antiplatelet therapy should be considered carefully.

Electrochemiluminescent Spin-Polarized Modulation by Magnetic Ions and Surface Plasmon Coupling.

Electrochemiluminescent modulation: Electrochemiluminescence (ECL) of CdS nanocrystal (NC) film-Au nanoparticle (NP) integrated system is controllably quenched by magnetic Co(2+) ions without external magnetic field owing to spin-polarized modulation of the electron-hole recombination caused by ferromagnetic alignment of Co(2+) in close proximity to Au NPs.

Surface-enhanced Raman spectroscopy for DNA detection by the self-assembly of Ag nanoparticles onto Ag nanoparticle-graphene oxide nanocomposites.

A novel surface-enhanced Raman scattering (SERS) sensing system which operates by the self-assembly of Ag nanoparticles (AgNPs) onto the nanocomposite of AgNPs and graphene oxide (AgNP-GO) in the presence of two complementary DNAs has been developed. In this system, AgNP-GO serves as a SERS-active substrate. The AgNPs with the modification of non-fluorescent 4-mercaptobenzoic acid (4-MBA) act as highly efficient Raman probes for DNA hybridization. When probe DNAs on AgNP-GO are complementary to target DNAs on AgNPs functionalized with 4-MBA, the DNA hybridization occurring directs the self-assembly of AgNPs onto AgNP-GO, leading to the creation of SERS hot spots. Due to the fact that partial 4-MBA molecules are located in the region of the hot spots, their SERS signals are greatly enhanced, indicating successful DNA hybridization. It is noteworthy that the size of AgNPs contributes significantly to the enhancement of SERS activity. The detection limit of the target DNAs at the pM level can be achieved through the self-assembly of large sized AgNPs onto AgNP-GO. More importantly, the AgNP-AgNP-GO system shows reproducible SERS signals in proportion to the logarithm of the target DNA concentrations spanning from 10(-6) to 10(-12) M and the excellent capability for multiplex DNA detection.

Functional neuroplasticity of facilitation and interference effects on inhibitory control following 3-month physical exercise in aging.

Preservation of executive function, like inhibition, closely links to the quality of life in senior adults. Although neuroimaging literature has shown enhanced inhibitory function followed by aerobic exercise, current evidence implies inconsistent neuroplasticity patterns along different time durations of exercise. Hence, we conducted a 12-week exercise intervention on 12 young and 14 senior volunteers and repeatedly measured the inhibitory functionality of distinct aspects (facilitation and interference effects) using the numerical Stroop task and functional Magnetic Resonance Imaging. Results showcased improved accuracy and reduced reaction times (RT) after 12-week exercise, attributed to frontoparietal and default mode network effects. In young adults, the first phase (0 to six weeks) exercise increased the activation of the right superior medial frontal gyrus, associated with reduced RT in interference, but in the second intervention phase (six to twelve weeks), the decreased activation of the left superior medial frontal gyrus positively correlated with reduced RT in facilitation. In senior adults, the first six-week intervention led to reduced activations of the inferior frontal gyrus, inferior parietal gyrus, and default mode network regions, associated with the reduced RT in interference. Still, in the second intervention phase, only the visual area exhibited increased activity, associated with reduced RT in interference. Except for the distinctive brain plasticity between the two phases of exercise intervention, the between-group comparison also presented that the old group gained more cognitive benefits within the first six weeks of exercise intervention; however, the cognitive improvements in the young group occurred after six weeks of intervention. Limited by the sample size, these preliminary findings corroborated the benefits of aerobic exercise on the inhibitory functions, implying an age × exercise interaction on the brain plasticity for both facilitation and interference.

Research Progress on Structure-Activity Relationship of 1,8-Naphthalimide DNA Chimeras Against Tumor.

The development of 1,8-naphthalimide derivatives as cell probes, DNA targeting agents, and anti-tumor drugs is one of the research hotspots in the field of medicine. Naphthalimide compounds are a kind of DNA embedder, which can change the topological structure of DNA by embedding in the middle of DNA base pairs, and then affect the recognition and action of topoisomerase on DNA. Aminofide and mitonafide are the first 2 drugs to undergo clinical trials. They have good DNA insertion ability, can embed DNA double-stranded structure, and induce topoisomerase II to cut part of pBR322DNA, but not yet entered the market due to their toxicity. In this paper, the design and structure-activity relationship of mononaphthalimide and bisaphthalimide compounds were studied, and the relationship between the structure of naphthalimide and anti-tumor activity was analyzed and discussed. It was found that a variety of structural modifications were significant in improving anti-tumor activity and reducing toxicity.

Dredging wastewater discharge from shrimp ponds affects mangrove soil physical-chemical properties and enzyme activities.

Dredging wastewater discharge is a significant environmental concern for mariculture near mangrove ecosystems. However, little attention has been paid to its effects on the soil physical-chemical properties and enzyme activities in mangrove habitats. This study compared the soil physical-chemical properties and enzyme activities in the polluted area that received dredging wastewater from a shrimp pond with those in the control area without wastewater to explore the effects of wastewater discharge on the soil physical-chemical properties and enzyme activities. Variations in soil physical-chemical properties and enzyme activities across different tidal flat areas and depths were also examined. The polluted area exhibited lower soil salinity (10.47 ± 0.58 vs. 15.64 ± 0.54) and moisture content (41.85 ± 1.03 % vs. 45.81 ± 1.06 %) than the control area. Wastewater discharge increased soil enzyme activities, (acid phosphatase, protease, and catalase), resulting in higher inorganic nitrogen (13.20 ± 0.00 µg g-1 vs. 11.60 ± 0.03 µg g-1) but lower total nitrogen (0.93 ± 0.01 mg g-1 vs. 1.62 ± 0.11 mg g-1) in the contaminated zone. From the control to polluted area, there was an approximate increase of 0.43 and 0.83 mg g-1 in soil total phosphorus and soluble phosphate, driven by increased acid phosphatase. However, soil humus and organic matter decreased by 0.04 and 1.22 %, respectively, because of wastewater discharge. The impact of wastewater discharge on the soil physical-chemical properties and enzyme activities was most pronounced in the landward and surface soil layers (0-5 cm). The results showed that wastewater discharge altered soil physical-chemical properties and enzyme activities, accumulating soil bioavailable nutrients (inorganic nitrogen and soluble phosphate), but at the cost of reduced soil quality, especially organic matter, further adversely affecting the overall health of mangrove ecosystems. Prioritizing the management of wastewater discharged from mariculture adjacent to mangrove forests is crucial for mangrove conservation.

(Z)-1-(2-Hy-droxy-eth-yl)-4-(2-meth-oxy-benzyl-idene)-2-methyl-1H-imidazol-5(4H)-one.

In the title compound, C14H16N2O3, an analog of the chromophore in green fluorescent protein, the meth-oxy-phenyl substituent and the imidazole N adopt a Z conformation with respect to the C=C bond. Aside from the hy-droxy-ethyl group, the mol-ecule is approximately planar, with the five- and six-membered ring planes forming a dihedral angle of 9.3 (1)°. An intra-molecular C-H⋯N contact occurs. In the crystal, O-H⋯N hydrogen bonds link the mol-ecules, forming chains along the b-axis direction. C-H⋯O hydrogen bonds are also observed.

A knowledge graph-based analytical model for mining clinical value of drug stress echocardiography for diagnosis, risk stratification and prognostic evaluation of coronary artery disease.

The three major techniques for clinically diagnosing coronary heart disease, including angina associated with myocardial ischemia, are coronary angiography, myocardial perfusion imaging, and drug stress echocardiography. Compared to the first two methods, which are invasive or involve the use of radionuclides, drug stress echocardiography is increasingly used in clinical practice due to its non-invasive, low-risk, and controllable nature, and wide applicability. We developed a novel methodology to demonstrate knowledge graph-based efficacy analysis of drug stress echocardiography as a complement to traditional meta-analysis. By measuring coronary flow reserve (CFR), we discovered that regional ventricular wall abnormalities (RVWA) and drug-loaded cardiac ultrasound can be used to detect coronary artery disease. Additionally, drug-loaded cardiac ultrasound can be used to identify areas of cardiac ischemia, stratify risks, and determine prognosis. Furthermore, adenosine stress echocardiography(ASE) can determine atypical symptoms of coronary heart disease with associated cardiac events through CFR and related quantitative indices for risk stratification. Using a knowledge graph-based approach, we investigated the positive and negative effects of three drugs - Dipyridamole, Dobutamine, and Adenosine - for coronary artery disease analysis. Our findings show that Adenosine has the highest positive effect and the lowest negative effect among the three drugs. Due to its minimal and controlled side effects, and high sensitivity for diagnosing coronary microcirculation disorders and multiple lesions, adenosine is frequently used in clinical practice.

Improving cleaner production of human activities to mitigate total petroleum hydrocarbons accumulation in coastal environment.

The marine coast is an important ecological transitional boundary but easily suffers from human intervention. Total petroleum hydrocarbons (TPHs) are ubiquitous along the coast. However, the influence of anthropogenic and natural factors on TPHs distribution remains unclear. This study sampled surficial sediment (N = 243) from the coasts of the largest peninsula-Leizhou Peninsula, in Southern China. We found that land-based discharge, sea traffic, and sediment type significantly (p < 0.05) drive the accumulation of TPHs. We observed that TPHs increased by 1.036 µg · g-1 (exp[αi] = exp. [0.0355]) of its original value with the addition of one more boat on the wharf. Although the average TPHs were at a moderate level (124.68, ND-1536.14, µg · g-1) and risk, 'Blue Carbon' ecosystems, i.e., mangroves (224.84, ND - 1441.13, µg · g-1, p < 0.001) were more severely polluted. Cleaner production policy should be applied to mitigate TPHs discharging trend from coastal areas.