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Two new austocystin analogs, austocystin P (1) and austocystin Q (2), along with fourteen known compounds (3-16) were isolated from the fermentation extract of Aspergillus sp. WHUF05236. The planar structures of 1 and 2 were elucidated through 1D, 2D NMR and MS analyses. Their absolute configurations were determined by the time-dependent density functional (TDDFT)-ECD calculation. Compounds 3, 11, and 12 exhibited antimicrobial activities against Helicobacter pylori with MIC values ranging from 20.00 to 43.47 μM. Compounds 3, 6, and 7 showed cytotoxicities against the human colon cancer cell lines Hct-116 with IC

Background The exact prevalence and impact of cardiac injury in hospitalized patients with coronavirus disease 2019 (COVID‐19) is still controversial. Hence, we aim to investigate prevalence of cardiac injury and its impact on the outcomes in patients with COVID‐19. Hypothesis Cardiac injury is common and associated with higher risk of death. Methods We searched the Cochrane Library, PubMed, MedRxiv, and EMBASE databases from December 2019 to July 15, 2020 for studies that evaluated the prevalence and impact of cardiac injury on COVID‐19. This study has been registered with PROSPERO (International prospective register of systematic reviews)‐registration number‐CRD‐42020186120. Results Twenty‐one studies including 6297 participants were identified. The proportions of cardiac injury were 22%, 28% among hospitalized patients with COVID‐19 or severe COVID‐19 patients, respectively. The incidences of cardiac injury in advance age (>60 years) (30%) was about two‐fold than young patients (

Nifekalant has been used in the treatment of atrial arrhythmia recently. However, there is no consensus on the preferable nifekalant dose to treat atrial fibrillation (AF). The purpose of this study was to explore efficacy and safety of different doses of nifekalant in the cardioversion of persistent AF. The study was a single-centre, randomized controlled trial. All subjects received nifekalant or placebo intravenously, and the nifekalant was given at the dosage of 0.3, 0.4 or 0.5 mg/kg. Primary efficacy end-point: compared with 0.3 mg group, the rate of cardioversion to sinus rhythm from AF in 0.4 and 0.5 mg group was higher. The 0.4 and 0.5 mg/kg doses were associated with a similar magnitude of efficacy (P > .05). Secondary efficacy end-point: termination rates of AF in the group of 0.4 mg and 0.5 mg were higher than 0.3 mg. Primary safety end-point: the rate of Torsades de Pointes or ventricular fibrillation was numerically lower in the 0.4 mg group than 0.5 mg group (P = .02). Secondary safety end-point: The rates of the majority of other common drug-related adverse events in the group of 0.5 and 0.4 mg were higher than the 0.3 mg group. A 0.4 mg/kg dose of intravenous nifekalant may be recommended during the radiofrequency ablation for persistent AF considering the benefit-risk profile.

The colinearity of canonical modular polyketide synthases, which creates a direct link between multienzyme structure and the chemical structure of the biosynthetic end-product, has become a cornerstone of knowledge-based genome mining. Here we report genetic and enzymatic evidence for the remarkable role of an enoylreductase in the polyketide synthase for azalomycin F biosynthesis. This internal enoylreductase domain, previously identified as acting only in the second of two chain extension cycles on an initial iterative module, is shown here also to catalyse enoylreduction in trans within the next module. The mechanism for this rare deviation from colinearity appears to involve direct cross-modular interaction of the reductase with the longer acyl chain, rather than backtransfer of the substrate into the iterative module, suggesting an additional and surprising plasticity in natural PKS assembly-line catalysis.

Heart failure (HF) is the end stage of most heart disease cases and can be initiated from multiple aetiologies. However, whether the molecular basis of HF has a commonality between different aetiologies has not been elucidated. To address this lack, we performed a three‐tiered analysis by integrating transcriptional data and pathway information to explore the commonalities of HF from different aetiologies. First, through differential expression analysis, we obtained 111 genes that were frequently differentially expressed in HF from 11 different aetiologies. Several genes, such as NPPA and NPPB, are early and accurate biomarkers for HF. We also provided candidates for further experimental verification, such as SERPINA3 and STAT4. Then, using gene set enrichment analysis, we successfully identified 19 frequently dysregulated pathways. In particular, we found that pathways related to immune system signalling, the extracellular matrix and metabolism were critical in the development of HF. Finally, we successfully acquired 241 regulatory relationships between 64 transcriptional factors (TFs) and 17 frequently dysregulated pathways by integrating a regulatory network, and some of the identified TFs have already been proven to play important roles in HF. Taken together, the three‐tiered analysis of HF provided a systems biology perspective on HF and emphasized the molecular commonality of HF from different aetiologies.

With the steadily increasing amount of leadless pacemaker implantations performed worldwide, it has called attention to the delivery difficulty in patients with severe large right heart. Nevertheless, limited studies have reported leadless pacemaker implantation in patients with tricuspid stenosis. Here, we report the successful implantation of leadless pacemaker in a 60-year-old female patient with giant right atrium and tricuspid valve stenosis. It is highlighted that leadless pacemaker should not be discouraged even if there are tricuspid valve stenosis and giant right atrium.

A new norditerpene named aculeaterpene A (1) and a new indone named aculeaindone A (2), along with eight known compounds 3-10 were isolated from the culture extract of Aspergillus aculeatinus WHUF0198. The structural characterization of compounds 1 and 2 were performed by spectroscopic analysis, including 1D and 2D NMR and HR-ESI-MS experiments, whereas the absolute configurations were determined by comparing their experimental or calculated ECD spectra. Compound 1 was the first report of fusicoccane-based norditerpene, in which the C-20 was degraded and tured into a hydroxy group.

Marine derived fungus has gained increasing ground in the discovery of novel lead compounds with potent biological activities including anti-inflammation. Here, we first report the characterization of one new sorbicillinoid (1) and fourteen known compounds (2-15) from the ethyl acetate (AcOEt) extract of a cultured mangrove derived fungus Penicillium sp. DM815 by UV, IR, HR ESI-Q-TOF MS, and NMR spectra. We then evaluated the anti-inflammatory effects of eleven sorbicillinoids (1-11) using cultured macrophage RAW264.7 cells. The results show that compound 9, and to a lesser degree compound 5, significantly inhibited the Gram-negative bacteria lipopolysaccharide (LPS)-induced upregulation of the inducible nitric oxide synthase (iNOS). Consistently, compounds 5 and 9 significantly reduced the level of nitric oxide (NO), the product of iNOS, induced by LPS. We further show that these two compounds dose-dependently inhibited LPS-triggered iNOS expression and NO production, but had no effect on proliferation of RAW264.7 cells in the presence of LPS. In conclusion, our study identifies novel and known sorbicillinoids as potent anti-inflammatory agents, holding the promise of developing novel anti-inflammation treatment in the future.

An association among the use of angiotensin converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) with the clinical outcomes of coronavirus disease 2019 (COVID-19) is unclear. PubMed, EMBASE, MedRxiv, and BioRxiv were searched for relevant studies that assessed the association between application of ACEI/ARB and risk of COVID-19, inflammation level, severity COVID-19 infection, and death in patients with COVID-19. Eleven studies were included with 33 483 patients. ACEI/ARB therapy might be associated with the reduced inflammatory factor (interleukin-6) and elevated immune cells counts (CD3, CD8). Meta-analysis showed no significant increase in the risk of COVID-19 infection (odds ratio [OR]: 0.95, 95%CI: 0.89-1.05) in patients receiving ACEI/ARB therapy, and ACEI/ARB therapy was associated with a decreased risk of severe COVID-19 (OR: 0.75, 95%CI: 0.59-0.96) and mortality (OR: 0.52, 95%CI: 0.35-0.79). Subgroup analyses showed among the general population, ACEI/ARB therapy was associated with reduced severe COVID-19 infection (OR: 0.79, 95%CI: 0.60-1.05) and all-cause mortality (OR: 0.31, 95%CI: 0.13-0.75), and COVID-19 infection (OR: 0.85, 95% CI: 0.66-1.08) were not increased. Among patients with hypertension, the use of an ACEI/ARB was associated with a lower severity of COVID-19 (OR: 0.73, 95%CI: 0.51-1.03) and lower mortality (OR: 0.57, 95%CI: 0.37-0.87), without evidence of an increased risk of COVID-19 infection (OR: 1.00). On the basis of the available evidence, ACEI/ARB therapy should be continued in patients who are at risk for, or have COVID-19, either in general population or hypertension patients. Our results need to be interpreted with caution considering the potential for residual confounders, and more well-designed studies that control the clinical confounders are necessary to confirm our findings.

Sugar O-methylation is a ubiquitous modification in natural products and plays diverse roles. This realization has inspired many attempts to search for novel methyltransferases. Chalcomycins are a group of 16-membered macrolides containing two methylated sugars that require three methyltransferases for their biosynthesis. Here, we identified that AlmCII, a sugar O-methyltransferase belonging to the TylF family that was previously only known to methylate sugars with a 4'-hydroxy group, can methylate a 4',6'-dideoxysugar during the biosynthesis of chalcomycins. An in vitro enzymatic assay revealed that AlmCII is divalent metal-dependent with an optimal pH of 8.0 and optimal temperature of 42 °C. Moreover, the 3'-O-demethylated chalcomycins exhibit less than 6 % of the antibacterial activity of their parent compounds. This is the first report demonstrating that a TylF family O-methyltransferase can use a 4'-deoxy sugar as a substrate and highlighting the importance of this methylation for the antibacterial activity of chalcomycins.

ZFAS1 is one of cardiac-specific or cardiac-related lncRNAs. This study was to explore the functional involvement of ZFAS1 and its regulatory role in AMI. In this study, the models of AMI rat and myocardial cell cultured under hypoxia were made. The expression of ZFAS1 and miR-150 of myocardial infarction tissue or cardiac myocytes was determined by quantitative real time PCR. The regulatory role of ZFAS1 on miR-150 was examined by RNA pull down assay. The effect of miR-150 or ZFAS1 expression on cell viability was analyzed by MTT assay. The relative expression of ZFAS1 in the myocardium infracted zone and border zone was significantly upregulated at 1-48 h of AMI rats, but it downregulated at 1 week and 2 weeks; miR-150 was significantly downregulated at AMI-1-48 h and upregulated at 1 and 2 weeks after model establishment. The result of RNA pull down assay indicated that ZFAS1 could interact directly with miR-150. C-reactive protein (CRP) was regulated by ZFAS1/miR-150 axis and negatively targeted by miR-150. Hypoxia caused the decrease of cell viability and the upregulation of CRP at mRNA and protein levels; whereas this upregulation could be attenuated by miR-150 mimic or si-ZFAS1 in H9C2 cells and cardiomyocytes. Knockdown of ZFAS1 or miR-150 overexpression effectively relieved AMI-induced myocardial infarction in AMI-1 week rats. The ZFAS1/miR-150 axis was involved in the molecular mechanism of AMI induced cardiomyocytes apoptosis via regulating CRP. J. Cell. Biochem. 118: 3281-3289, 2017. © 2017 Wiley Periodicals, Inc.

Detailed analysis of the modular Type I polyketide synthase (PKS) involved in the biosynthesis of the marginolactone azalomycin F in mangrove Streptomyces sp. 211726 has shown that only nineteen extension modules are required to accomplish twenty cycles of polyketide chain elongation. Analysis of the products of a PKS mutant specifically inactivated in the dehydratase domain of extension‐module 1 showed that this module catalyzes two successive elongations with different outcomes. Strikingly, the enoylreductase domain of this module can apparently be “toggled” off and on : it functions in only the second of these two cycles. This novel mechanism expands our understanding of PKS assembly‐line catalysis and may explain examples of apparent non‐colinearity in other modular PKS systems.

Aldgamycins are 16-membered macrolide antibiotics with a rare branched-chain sugar d-aldgarose or decarboxylated d-aldgarose at C-5. In our efforts to clone the gene cluster for aldgamycins from a marine-derived Streptomyces sp. HK-2006-1 capable of producing both aldgamycins and chalcomycins, we found that both are biosynthesized from a single gene cluster. Whole-genome sequencing combined with gene disruption established the entire gene cluster of aldgamycins: nine new genes are incorporated with the previously identified chalcomycin gene cluster. Functional analysis of these genes revealed that almDI/almDII, (encoding α/β subunits of pyruvate dehydrogenase) triggers the biosynthesis of aldgamycins, whereas almCI (encoding an oxidoreductase) initiates chalcomycins biosynthesis. This is the first report that aldgamycins and chalcomycins are derived from a single gene cluster and of the genetic basis for bifurcation in their biosynthesis.

Several studies have investigated the role of physical fitness in atrial fibrillation (AF), but the results remain controversial. We aimed to estimate the association between physical fitness and risk of AF. We comprehensively retrieved data from the Cochrane Library, PubMed, and Embase databases until February 29, 2016, for studies evaluating the association of physical fitness with the risk of AF. Data were abstracted from included studies, and effect estimates were pooled using a random-effects model. Six studies with a total of 205 094 participants and 15 919 AF cases fulfilled the inclusion criteria. When physical fitness was assessed as a continuous variable, per incremental increase of physical fitness was associated with a 9% reduced risk of AF (risk ratio [RR]: 0.91, 95% confidence interval [CI]: 0.84-1.00, P = 0.05). When physical fitness was assessed as a categorical variable, the risk of AF was significantly reduced (RR: 0.51, 95% CI: 0.28-0.91, P = 0.02) in individuals with the highest level of physical fitness compared with those with the lowest level. The intermediate vs the lowest level of physical fitness was associated with a 28% reduced risk of AF (RR: 0.72, 95% CI: 0.56-0.93, P = 0.01). The sensitivity analysis indicated that these results were stable. Notably, there was evidence of statistical heterogeneity across studies; therefore, we should interpret the results cautiously. In conclusion, published literature supports that a higher level of physical fitness is associated with a lower risk of AF. Further studies should be performed to confirm these findings.

Several studies investigated the role of physical activity in atrial fibrillation (AF), but the results remain controversial. We aimed to estimate the association between physical activity and incident AF, as well as to determine whether a sex difference existed. We systematically retrieved relevant studies from Cochrane Library, PubMed, and ScienceDirect through December 1, 2015. Data were abstracted from eligible studies and effect estimates pooled using a random-effects model. Thirteen prospective studies fulfilled inclusion criteria. For primary analysis, neither total physical activity exposure (relative risk [RR]: 0.98, 95% confidence interval [CI]: 0.90-1.06, P = 0.62) nor intensive physical activity (RR: 1.07, 95% CI: 0.93-1.25, P = 0.41) was associated with a significant increased risk of AF. In the country-stratified analysis, the pooled results were not significantly changed. However, in the sex-stratified analysis, total physical activity exposure was associated with an increased risk of AF in men (RR: 1.18, 95% CI: 1.02-1.37), especially at age

Background No pooled analysis has been undertaken to assess the efficacy and safety of the non-vitamin K antagonist oral anticoagulants (NOACs) compared with warfarin in the subgroup of patients with atrial fibrillation (AF) and heart failure (HF), including edoxaban data from recent randomized controlled trials (RCTs). Methods Comprehensive literature searches were conducted using the Cochrane Library, MEDLINE, and Scopus databases from inception to April 2015. Statistical analyses were performed using RevMan 5.3 software. Results Four RCTs were included: 19 122 of 32 512 AF patients with HF were allocated to a NOAC (13 384 receiving single-/high-dose NOAC regimens), and 13 390 to warfarin. Among AF patients with HF, single/high-dose NOACs significantly reduced the risk of stroke/systemic embolic (SE) events by 14% [odds ratio0.86, 95% confidence interval (CI) 0.76–0.98), and had a 24% lower risk of major bleeding(OR 0.76, 95% CI 0.67–0.86). For low-dose NOAC regimens, comparable efficacy to warfarin for stroke or SE events (OR 1.02, 95% CI 0.86–1.21) and a non-significant trend for lower major bleeding was observed. Regardless of high- or low-dose NOAC, the incidences of both major bleeding and stroke/SE in AF patients with HF were similar to those without HF. Atrial fibrillation patients with HF on NOACs had a 41% lower risk of intracranial haemorrhage compared with those without HF (OR 0.59, 95% CI 0.40–0.87). Conclusion Among AF patients with HF, single-/high-dose NOAC regimens have a better efficacy and safety profile, but low-dose regimens had similar efficacy and safety to warfarin. NOACs were similarly effective or even safer (less intracranial haemorrhage) in AF patients with HF compared with those without HF.

Our objective was to compare the diagnostic accuracy between the HAS-BLED score and any of HEMORR2 HAGES, ATRIA, CHADS2 , or CHA2 DS2 -VASc scores in anticoagulated patients with atrial fibrillation. We systematically searched the Cochrane Library, MEDLINE, PubMed, and Embase databases for relevant studies. Data were extracted and analyzed according to predefined clinical endpoints. Eleven studies were identified. Discrimination analysis demonstrates that HAS-BLED has no significant C-statistic differences for bleeding risk prediction compared with ATRIA or HEMORR2 HAGES, but it has significant differences compared with CHADS2 or CHA2 DS2 -VASc. The significant positive net reclassification improvement and integrated discrimination improvement values also show that HAS-BLED is superior to that of any of HEMORR2 HAGES, ATRIA, CHADS2 , or CHA2 DS2 -VASc scores. According to calibration analysis of HAS-BLED, it overpredicts the risk of bleeding in the low (risk ratio [RR]: 1.16, 95% confidence interval [CI]: 0.63-2.13, P = 0.64) risk stratification but underpredicts that in the moderate (RR: 0.66, 95% CI: 0.51-0.86, P = 0.002) and high (RR: 0.88, 95% CI: 0.70-1.10, P = 0.27) risk stratifications. The HAS-BLED score not only performs better than the HEMORR2 HAGES and ATRIA bleeding scores, but it also is superior to the CHADS2 and CHA2 DS2 -VASc stroke scores for bleeding prediction. The HAS-BLED score should be the optimal choice to assess major bleeding risk in clinical practice.

Two new meroterpenes, ‘acetoxydehydroaustin B’ (1) and ‘1,2-dihydro-acetoxydehydroaustin B’ (2) were isolated in the form of a mixed crystal from the mangrove endophytic fungus Aspergillus sp. 085241B. Their structures and absolute configurations were determined by extensive analysis of their spectra and X-ray diffraction data. In a preliminary bioassay, the mixed crystal did not exhibit activities against cancer cell lines of MDA-MB-435, SKBR3, HepG2, HEP3B, PC-3, and A549, as well as against α-glucosidase and tyrosinase.

Azalomycin F(4a) 2-ethylpentyl ester (1) and Azalomycin F(5a) 2-ethylpentyl ester (2), two new macrocyclic lactones, along with three known compounds of Azalomycins F(3a) (3), F(4a) (4) and F(5a) (5), were identified from metabolites of Streptomyces sp. 211726 isolated from mangrove rhizosphere soil. The complete (1)H and (13)C assignments of these compounds were achieved by using (1)H, (13)C, DEPT, HSQC, (1)H-(1)H COSY and HMBC spectra, and the relative stereochemistry of 5 was first elucidated on the basis of proton-proton coupling constants, NOESY and IR spectra. Moreover, some errors in the (1)H and (13)C assignments published of 3, 4 and 5 were found and revised. 1 and 2 were active against Candida albicans, and exhibited moderate cytotoxicity against HCT-116 cell line.

Two new oxidized sterols 1 and 2 were obtained from the active fraction of a mangrove fungus Aspergillus awamori isolated from the soils around the mangrove plant Acrostichum speciosum. Their structures were elucidated using spectroscopic methods as 22E-7α-methoxy-5α,6α-epoxyergosta-8(14),22-dien-3β-ol (1) and 22E-3β-hydroxy-5α,6α,8α,14α-diepoxyergosta-22-en-7-one (2). The NMR data and complete assignments for both DMSO-d6 and CDCl3 were given. Their cytotoxic activity against A549 cell line was evaluated. Furthermore, the detailed conformation analysis for ring B (cyclohexene oxide system) of sterol 1 was given on the basis of NOEs. The endo-boat conformation was considered as the preferred conformation for ring B rather than half-chair conformation. Copyright © 2009 John Wiley & Sons, Ltd.

The polyhydroxylated ergostane-type sterol 9, its derivatives 10–15, and the fatty acid esters 1–8 were isolated from a fungus strain which was collected from mangrove areas at Wenchang, Hainan Province, P. R. China, exhibited potent cytotoxic activity, and was identified as Aspergillus awamori. The structures of 1–15 were elucidated by spectroscopic and chemical methods. Among them, the six steryl esters 1–6 of fatty acids were new compounds, i.e., (3β,5α,6α,22E)-ergosta-7,22-diene-3,5,6-triol 6-palmitate (1), (3β,5α,6α,22E)-ergosta-7,22-diene-3,5,6-triol 6-stearate (2), (3β,5α,6α,22E)-ergosta-7,22-diene-3,5,6-triol 6-oleate (3), (3β,5α,6α,22E)-ergosta-7,22-diene-3,5,6-triol 6-linoleate (4), (3β,5α,6β,22E)-ergosta-7,22-diene-3,5,6-triol 6-palmitate (5), and (3β,5α,6β,22E)-ergosta-7,22-diene-3,5,6-triol 6-stearate (6). The related known fatty acids stearic acid (=octadecanoic acid) and palmitic acid (=octadecanoic acid) were also obtained. A speculative biogenetic relationship of the metabolites is proposed. The known polyhydroxylated sterols and derivatives showed cytotoxic activities, in agreement with earlier reports. The cytotoxic activities against B16 and SMMC-7721 cell lines of the new steryl esters 1–6 by the MTT method were weak.

A new surfactin isomer (1) was isolated from a mangrove bacteria strain ‘Bacillus sp’. Its structure was identified, and full assignments of 1H and 13C NMR spectral data were achieved for the first time by a combination of mass spectrometry and 1D and 2D NMR experiments including DEPT, 1H1H COSY, HSQC, HMBC, TOCSY, ROESY, and HSQC-TOCSY. The NMR spectral data of eight known analogs (2–9) are also reported. Copyright © 2007 John Wiley & Sons, Ltd.

Introduction: Brugada syndrome is characterized by sudden death secondary to malignant arrhythmias and the presence of ST segment elevation in leads V1 to V3 of patients with structurally normal hearts. This ECG pattern often is concealed but can be unmasked using potent sodium channel blockers. Like congenital long QT syndrome type 3 (LQT3) and sudden unexpected death syndrome, Brugada syndrome has been linked to mutations in SCN5A. Methods and Results: We screened a large European family with Brugada syndrome. Three members (two female) had suffered malignant ventricular arrhythmias. Ten members showed an ECG pattern characteristic of Brugada syndrome at baseline, and eight showed the pattern only after administration of ajmaline (total 12 female). Haplotype analysis revealed that all individuals with positive ECG at baseline shared the SCN5A locus. Sequencing of SCN5A identified a missense mutation, R367H, previously associated with sudden unexpected death syndrome. Two of the eight individuals who displayed a positive ECG after the administration of ajmaline, but not before, did not have the R367H mutation, and sequencing analysis failed to identify any other mutation in SCN5A. The R367H mutation failed to generate any current when heterologously expressed in HEK cells. Conclusion: Our results support the hypothesis that (1) sudden unexpected death syndrome and Brugada syndrome are the same disease; (2) male predominance of the phenotype observed in sudden unexpected death syndrome does not apply to this family, suggesting that factors other than the specific mutation determine the gender distinction; and (3) ajmaline may provide false-positive results. These findings have broad implications relative to the diagnosis and risk stratification of family members of patients with the Brugada syndrome. (J Cardiovasc Electrophysiol, Vol. 15, pp. 64-69, January 2004)

Epsilon wave, which is a major diagnosis criterion for arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVD/C), is defined as small amplitude potentials. The present case is a 49-year-old man with a history of syncope and palpitations for 6 months. The ECG documented ventricular tachycardia (VT) when the patient has palpitations. However, there has been a giant epsilon wave in sinus rhythm. Electroanatomic mapping also has a prominent double potential identified on ABL catheter. The amplitude of epsilon wave reached 0.9 mV, which might be the maximum epsilon wave until now.

Currently, most thrombolytic agents are limited by short circulation time and excessive dose needed for clinical therapy, which increases lethal risk for intracranial hemorrhage. Here, a near-infrared-triggered, controlled-release system, using gold@mesoporous silica core–shell nanospheres (Au@MSNs) with phase-changed material 1-tetradecanol, is formulated to release urokinase plasminogen activators (uPA) on demand. The prepared system presents a sensitive system for releasing uPA, owing to an elevated temperature created by Au@MSNs-induced photothermal effect. For in vitro study, a 3D printed vein vasculature is designed and fabricated to simulate the thrombolysis of system in blood vessel. Murine tail thrombus model is also built to evaluate thrombolysis in vivo. Consequently, localized hyperthermia is validated to possess an effective enhancement for thrombolysis. Therefore, according to the results, the fabricated system demonstrates two aspects of potential superiority: controlled uPA release for reducing risk of side effects, and hyperthermia-enhanced thrombolysis locally for decreasing drug dosage. Assisted with thermal thrombolysis, the present formulated system shows a high efficiency, on-demand drug release, and thus a safer protocol for thrombolytic therapy, which fits the developing trends of precision medicine.

Short QT Syndrome and Atrial Fibrillation. Background: The short QT syndrome is a newly described clinical entity characterized by the presence of a short QT interval associated with cardiac tachyarrhythmias including sudden cardiac death at a young age in otherwise healthy individuals. A genetic basis has been identified linking the disease to mutations in KCNH2 in the familial forms and a mutation in KCNQ1 in a sporadic form of the disease. Methods and Results: We identified a family with short QT syndrome with a high incidence of paroxysmal atrial fibrillation in their members and no known history of sudden cardiac death. QT interval ranged from 225 to 240 ms within normal heart rate ranges in the affected individuals. Programmed electrical stimulation (PES) was performed in all affected members, which revealed a remarkably short atrial and ventricular refractory period, and inducibility of atrial and ventricular fibrillation. Treatment with propafenone has maintained the individuals free of atrial fibrillation to date. Genetic analysis identified a missense mutation (C to G substitution at nucleotide 1764) which resulted in the amino acid change (N588K) in KCNH2. This mutation had been previously described in two other families with a high incidence of sudden cardiac death. Conclusions: Our study confirms that N588K is a hotspot for familial form of the short QT syndrome. The disease is clinically heterogeneous, as indicated by the fact that, in the three families with the same mutation, there is a wide range of symptoms, varying from atrial to ventricular fibrillation and sudden death. While the implantation of a defibrillator appears warranted due to the inducibility at PES, the clinical follow-up provides indication that the class Ic agent propafenone could be effective to prevent episodes of paroxysmal atrial fibrillation.

The novel quinazolinone alkaloids (I) and (II) are isolated along with seven known analogues from the BuOH extract of the marine-derived bacterium Bacillus cereus.

Two new epimeric pairs of iridoid scyphiphin A(1) (1a), A2 (1b) and scyphiphin B-1 (2a), B-2 (2b) were isolated from Scyphiphora hydrophyllacea Gaertn. F. Their structures were elucidated by spectroscopic methods. The mixture of scyphiphin B-1 and scyphipbin B-2 showed moderate cytotoxicity against human hepatoma SMMC-7721 cell line in vitro by MTT method. (c) 2007 Wen Li Mei. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

Objective: Recent research shows that sodium channel gene mutation is one of the disease-causing gene in ischemia-induced ventricular arrhythmia. In this study, in order to reveal the relationship between ischemia-induced ventricular arrhythmia and potassium channel mutation. Methods: 23 patients with ischemia-induced ventricular arrhythmia were selected. 5ML peripheral blood was taken and DNA extracted. 11 candidate genes including HERG, KCNQ1, KCNE1, KCNE2, KCNJ2, KCNJ3, KCNJ8, KCNJ11, KCNJ12, KCND3 and KCNA5 were screened with direct sequencing methods. Results: 10 Potassium channel SNP have been found. The G216G is a novel SNP, which shows a change from T base to C base at the position of 1353 on the third exon of KCNJ12 gene. The SNP distribution from KCNJ12-Q192H, KCNJ12-P156L, HERG-I489I, KV1.5-P513P, Kir2.1-L382L, Kir6.2-V337I, KCNQ1-P448R and KCNQ1-S546S are similar with reported. The SNP of F513F is at the position of 1545 C base substitution T base on the seventh exon of the HERG gene. 5 patients have been found the SNP of F513F while 44 in the control group. Chi-square test shows that there is a difference in the incidence of the F513F SNP between the two groups. Conclusion: No potassium channel gene mutation has been found. A novel SNP of KCNJ12-G216G was discovered in Chinese people. The SNP of HERG-F513F might be a predisposing factor in ischemia-induced ventricular arrhythmia.