Conformation- and Coordination Mode-Dependent Stimuli-Responsive Salicylaldehyde Hydrazone Zn(II) Complexes.

Luminescent Zn(II) complexes that respond to external stimuli are of wide interest due to their potential applications. Schiff base with O,N,O-hydrazone shows excellent luminescence properties with multi-coordination sites for different coordination modes. In this work, three salicylaldehyde hydrazone Zn(II) complexes (1, 2a, 2b) were synthesized and their stimuli-responsive behaviors in different states were explored. Only complex 1 exhibits reversible and self-recoverable photochromic and photoluminescence properties in solution. This may be due to the configuration eversion and the excited-state intramolecular proton transfer (ESIPT) process. In the solid state, 2a has obvious mechanochromic luminescence property, which is caused by the destruction of intermolecular interactions and the transformation from crystalline state to amorphous state. 2a and 2b have delayed fluorescence properties due to effective halogen bond interactions in structures. 2a could undergo crystal-phase transformation into its polymorphous 2b by force/vapor stimulation. Interestingly, 2b shows photochromic property, which can be attributed to the electron transfer and generation of radicals induced by UV irradiation. Due to different conformations and coordination modes, the three Zn(II) complexes show different stimuli-responsive properties. This work presents the multi-stimuli-responsive behaviors of salicylaldehyde hydrazone Zn(II) complexes in different states and discusses the response mechanism in detail, which may provide new insights into the design of multi-stimuli-responsive materials.

Multistimulus Response of Two Tautomeric Zn(II) Complexes and Their White-Light Emission Based on Different Mechanisms.

A triphenylamine (TPA)-based 2H-quinazoline Zn(II) complex (Q-TPA-Zn) exhibiting dual fluorescence and phosphorescence emission in the solid state was designed and prepared. It possesses mechanochromic luminescence and thermochromic luminescence properties. In the solid state, the white afterglow luminescence could be observed at 77 K (CIExy: 0.27, 0.33) while cyan luminescence could be observed at 297 K. After thermolysis at 300 °C, Q-TPA-Zn could be transformed into Schiff base complex S-TPA-Zn with white fluorescence in the powder state (CIExy: 0.32, 0.38), in methanol (CIExy: 0.32, 0.39), and in dimethylformamide (CIExy: 0.26, 0.32) at room temperature. This arises from dual emission of normal* emission and tautomeric* emission induced by excited-state intramolecular proton transfer (ESIPT) from the benzimidazole NH group to the Schiff base N atom. Q-TPA-Zn could also be transformed into its isomeric form, S-TPA-Zn, through photochemical ring-opening reaction upon irradiation under 365 nm in the solution, exhibiting high-contrast photochromic luminescence. Interestingly, S-TPA-Zn could further be transformed into its zwitterionic isomer after continuous irradiation. The same ring-opening reaction could also take place for the orgainc compound Q-TPA via heating or 365 nm irradiation. The ring-opening reaction mechanism and ESIPT emission were interpreted via theoretical calculation.

Theoretical study of the mechanism of the manganese catalase KatB.

The mechanism of the H2O2 disproportionation catalyzed by the manganese catalase (MnCat) KatB was studied using the hybrid density functional theory B3LYP and the quantum chemical cluster approach. Compared to the previous mechanistic study at the molecular level for the Thermus thermophilus MnCat (TTC), more modern methodology was used and larger models of increasing sizes were employed with the help of the high-resolution X-ray structure. In the reaction pathway suggested for KatB using the Large chemical model, the O-O homolysis of the first substrate H2O2 occurs through a µ-η1:η1 coordination mode and requires a barrier of 10.9 kcal/mol. In the intermediate state of the bond cleavage, two hydroxides form as terminal ligands of the dimanganese cluster at the Mn2(III,III) oxidation state. One of the two Mn(III)-OH- moieties and a second-sphere tyrosine stabilize the second substrate H2O2 in the second-sphere of the active site via hydrogen bonding interactions. The H2O2, unbound to the metals, is first oxidized into HO2· through a proton-coupled electron transfer (PCET) step with a barrier of 9.5 kcal/mol. After the system switches to the triplet surface, the uncoordinated HO2· replaces the product water terminally bound to the Mn(II) and is then oxidized into O2 spontaneously. Transition states with structural similarities to those obtained for TTC, where µ-η2-OH-/O2- groups play important roles, were found to be higher in energy.

Droplet impact on heated powder bed.

The impact of droplets on a heated powder bed involves a wide range of phenomena with increasing complexity from spreading of liquid, to bubble nucleation, to more complex ones such as splashing, crater formation, and fluidization. In this study, we focus on the impact behaviors caused by elevation in temperature of the powder bed. We experimentally characterize the impact behaviors for wide ranges of the impact velocity and surface temperature of the powder bed. We reveal several phenomena specific to the impact on a heated powder bed such as rebound, ruptures of expanding liquid films, bubble nucleation, and fluidization. We also show that the maximum spreading diameter increases with the surface temperature of the powder bed and propose an empirical scaling law to describe such a relation.

A novel endocardial activation-derived predictor for focal paraseptal atrial tachycardias: Evidence from a multicenter cohort study.

BACKGROUND: The electrocardiogram-based algorithm for predicting paraseptal atrial tachycardia (PSAT) is limited by the significant overlaps in P-wave morphology originating from various paraseptal sites. OBJECTIVES: The goals of this study were to investigate the endocardial activation characteristics of PSAT and to seek an endocardial activation-derived predictor for the ablation site. METHODS: Forty-four patients [11 men (25%); mean age 62.6 ± 14.7 years] with PSAT ablation in 4 tertiary medical centers were assigned to 3 groups according to the ablation site: right atrial (RA) para-Hisian region (group 1, n = 10), noncoronary cusp (NCC) (group 2, n = 13), and left atrial (LA) paraseptal area (group 3, n = 21). Multiple-chamber activation mapping was performed guided by a 3-dimensional navigation system. The discrepancies in the earliest activation time between 2 of 3 chambers (ΔRA-LA, ΔRA-NCC, and ΔLA-NCC) were calculated in each group and used for pairwise comparisons. RESULTS: There was a significant difference in ΔRA-LA, ΔRA-NCC, and ΔLA-NCC among the 3 groups. ΔRA-LA was the only parameter that could consistently predict the ablation site of PSAT with good accuracy (area under the curve 1.000, sensitivity 100% and specificity 100%, and cutoff value 7 ms for predicting right para-Hisian or NCC ablation; area under the curve 0.974, sensitivity 92.3% and specificity 95.2%, and cutoff value -4 ms for predicting NCC or left paraseptal ablation). Based on 2 cutoff values, a 2-step algorithm was developed to predict the ablation site of PSAT with a positive predictive value of 95.4% and a negative predictive value of 97.0%. CONCLUSION: ΔRA-LA is a useful endocardial activation-derived parameter for predicting the successful ablation site of PSAT.

Novel germline GJA5/connexin40 mutations associated with lone atrial fibrillation impair gap junctional intercellular communication.

Atrial fibrillation (AF) is the most common form of sustained cardiac arrhythmia worldwide. Here, we investigate the molecular and cellular mechanisms of lone AF-linked germline mutations in the connexin40 (Cx40) gene, GJA5. The entire coding region of GJA5 was sequenced in 68 unrelated patients with lone AF. A novel germline heterozygous missense mutation in Cx40 (p.I75F) was identified in one index patient. The mutation was also present in the proband's father with lone AF but was not found in the unaffected family members who were examined and 200 unrelated healthy control individuals. Electrophysiological studies revealed no electrical coupling of the cell pairs expressing the mutant alone and a significant reduction in gap junction coupling conductance when the mutant was coexpressed with wild-type (wt) Cx40 or Cx43. Interestingly, another lone AF-linked Cx40 mutant p.L229M did not show any apparent coupling defect when expressed alone or together with wt Cx40 but specifically reduced the gap junction coupling when coexpressed with wt Cx43. This study is the first to demonstrate that the germline familial mutations in Cx40 impair the gap junctions through different mechanisms, which may predispose the mutant carriers to AF.

Evaluation of linear lesions in the left and right atrium in ablation of long-standing atrial fibrillation.

BACKGROUND: This randomized prospective study compared three ablation strategies in patients with long-standing persistent atrial fibrillation (LPeAF). It also explored the best procedural endpoint from among the following: circumferential pulmonary vein isolation (PVI) + left atrial (LA) linear lesions (roofline, mitral isthmus) + complex fractionated atrial electrogram (CFAE) ablation, PVI + LA linear lesions + cavotricuspid isthmus (CTI) ablation + CFAE ablation, and PVI + CFAE ablation. METHODS AND RESULTS: A total of 210 patients with LPeAF referred for catheter ablation were enrolled and randomized into three ablation groups. The patients in group A (n = 70) underwent PVI followed by LA linear and CFAE ablation; in 93% of patients the primary endpoint was achieved (five patients with incomplete linear lesions). Of the 70 patients in group B who were subjected to PVI followed by LA linear, CFAE, and CTI ablations, in 94% of patients the primary endpoint was achieved (four patients with incomplete linear lesions). All patients in group C (n = 70) successfully underwent PVI and CFAE ablation. Direct current cardioversion was performed upon PVI, CFAE elimination, and completion of linear lesions. Patients were followed-up for atrial tachyarrhythmia recurrence for at least 24 months. After a single ablation procedure, group C (36%) exhibited the lowest success compared with group A (54%) and group B (51%) (P = 0.06). At the mean follow-up of 32 ± 9 months after the final ablation procedure, 53 patients (76%) in group A, 53 (76%) in group B, and 41 (59%) in group C were in sinus rhythm without antiarrhythmic drugs (P = 0.03). CONCLUSIONS: In LPeAF, linear lesions in the LA help improve outcome of ablation, additional CTI ablation does not.

Efficacy and safety of catheter ablation for long-standing persistent atrial fibrillation in women.

OBJECTIVES: It is uncertain whether gender affects the outcomes of catheter ablation (CA) for atrial fibrillation (AF). The objective of the study is to evaluate the efficacy and safety of CA for long-standing persistent AF in women. METHODS: Between January 2010 and May 2011, 220 consecutive patients (73 females, 33.2%), with long-standing persistent AF who underwent CA were prospectively recruited. Gender-related differences in clinical presentation, periprocedural complications, and outcomes were compared. RESULTS: Women were less likely to have lone AF than men (27.4% vs 47.6%; P = 0.004). The incidence of rheumatic heart disease was higher in women (19.2% in women vs 1.4% in men; P < 0.001). Women had a lower initial ablation success rate than men (35.6% vs 57.1%; P = 0.003). Hematomas occurred more often in women (6.8% in women vs 0.7% in men; P = 0.027). A Cox regression analysis demonstrated total duration of AF (per month, hazard ratio [HR] 1.003, confidence interval [CI] 1.001-1.006; P = 0.006) and gender (HR 1.663, CI 1.114-2.485; P = 0.013) as the independent predictors for recurrence after the first CA. CONCLUSIONS: Women and long AF duration were closely related to the recurrence of AF after the first ablation in patients with long-standing persistent AF. Women also had a higher risk of vascular complications.

Angiotensin II increases CTGF expression via MAPKs/TGF-ß1/TRAF6 pathway in atrial fibroblasts.

The activation of transforming growth factor-ß1(TGF-ß1)/Smad signaling pathway and increased expression of connective tissue growth factor (CTGF) induced by angiotensin II (AngII) have been proposed as a mechanism for atrial fibrosis. However, whether TGFß1/non-Smad signaling pathways involved in AngII-induced fibrogenetic factor expression remained unknown. Recently tumor necrosis factor receptor associated factor 6 (TRAF6)/TGFß-associated kinase 1 (TAK1) has been shown to be crucial for the activation of TGF-ß1/non-Smad signaling pathways. In the present study, we explored the role of TGF-ß1/TRAF6 pathway in AngII-induced CTGF expression in cultured adult atrial fibroblasts. AngII (1 µM) provoked the activation of P38 mitogen activated protein kinase (P38 MAPK), extracellular signal-regulated kinase 1/2(ERK1/2) and c-Jun NH(2)-terminal kinase (JNK). AngII (1 µM) also promoted TGFß1, TRAF6, CTGF expression and TAK1 phosphorylation, which were suppressed by angiotensin type I receptor antagonist (Losartan) as well as p38 MAPK inhibitor (SB202190), ERK1/2 inhibitor (PD98059) and JNK inhibitor (SP600125). Meanwhile, both TGFß1 antibody and TRAF6 siRNA decreased the stimulatory effect of AngII on TRAF6, CTGF expression and TAK1 phosphorylation, which also attenuated AngII-induced atrial fibroblasts proliferation. In summary, the MAPKs/TGFß1/TRAF6 pathway is an important signaling pathway in AngII-induced CTGF expression, and inhibition of TRAF6 may therefore represent a new target for reversing Ang II-induced atrial fibrosis.

Theoretical Study of the Catalytic Mechanism of the Cu-Only Superoxide Dismutase.

The catalytic mechanisms for the wild-type and the mutated Cu-only superoxide dismutase were studied using the hybrid density functional B3LYP and a quantum chemical cluster approach. Optimal protonation states of the active site were examined for each stage of the catalytic cycle. For both the reductive and the oxidative half-reactions, the arrival of the substrate O2•- was found to be accompanied by a charge-compensating H+ with exergonicities of -15.4 kcal·mol and -4.7 kcal·mol, respectively. The second-sphere Glu-110 and first-sphere His-93 were suggested to be the transient protonation site for the reductive and the oxidative half-reactions, respectively, which collaborates with the hydrogen bonding water chain to position the substrate near the redox-active copper center. For the reductive half-reaction, the rate-limiting step was found to be the inner-sphere electron transfer from the partially coordinated O2•- to CuII with a barrier of 8.1 kcal·mol. The formed O2 is released from the active site with an exergonicity of -14.9 kcal·mol. For the oxidative half-reaction, the inner-sphere electron transfer from CuI to the partially coordinated O2•- was found to be accompanied by the proton transfer from the protonated His-93 and barrierless. The rate-limiting step was found to be the second proton transfer from the protonated Glu-110 to HO2- with a barrier of 7.3 kcal·mol. The barriers are reasonably consistent with experimental activities, and a proton-transfer rate-limiting step in the oxidative half-reaction could explain the experimentally observed pH-dependence. For the E110Q CuSOD, Asp-113 was suggested to be likely to serve as the transient protonation site in the reductive half-reaction. The rate-limiting barriers were found to be 8.0 and 8.6 kcal·mol, respectively, which could explain the slightly lower performance of E110X mutants. The results were found to be stable, with respect to the percentage of exact exchange in B3LYP.

Enhancement of Long-Lived Persistent Room-Temperature Phosphorescence and Anion Exchange with I- and SCN- via Metal-Organic Hybrid Formation.

An in-depth understanding of structure-property relationships and the construction of multifunctional stimuli-responsive materials are still difficult challenges. Herein, we discovered a 4,4'-bipyridinium derivative with both photochromism and dynamic afterglow at 77 K for the first time. A one-dimensional (1D) Cd(II) coordination polymer (1) assembled by only a 4,4'-bipyridinium derivative and cadmium chloride showed photochromism, room-temperature phosphorescence (RTP), and electrochromism. Interestingly, we found that 1 underwent single-crystal-to-single-crystal transformation during the anion exchange process, and the color of the crystal changed from colorless to yellow (1-SCN-) within 10 min. Complex 1 exhibited photochromism, whereas 1-SCN- did not. The difference in the photochromic behavior between the two complexes was ascribed to the electron transfer pathway between the carboxylate groups and viologen. The DFT calculation based on the crystal structure of 1-SCN- indicated that the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) were mainly located on bipyridine and cadmium atoms, eliminating the possibility of electron transfer, whereas for complex 1, electron transfer was probable from O and Cl atoms to pyridinium N atoms in viologen as demonstrated by density of states (DOS) calculations. In addition, complex 1 was successfully made into test paper for the rapid detection of I- and SCN- and displayed potential applications in inkless printing, multiple encryption, and anticounterfeiting.

A Four-Stepwise Electrocardiographic Algorithm for Differentiation of Ventricular Arrhythmias Originated from Left Ventricular Outflow Tract.

Several electrocardiographic algorithms have been proposed to identify the site of origin for the ventricular arrhythmias (VAs) from the left ventricular outflow tract (LVOT) versus right ventricular outflow tract. However, the electrocardiographic criteria for distinguishing VAs originated from the different sites of LVOT is lacking. We aimed to develop a simple and efficient ECG algorithm to differentiate LVOT VAs originated from the aortic root, AMC and LV summit. We analyzed 12-lead ECG characteristics of 68 consecutive patients who underwent successful radiofrequency catheter ablation of symptomatic VAs from LVOT. Patients were divided into RCC (right coronary cusp) group (n = 8), the L-RCC (the junction between the LCC and RCC) group (n = 21), the LCC (left coronary cusp) group (n = 24), the aortomitral continuity (AMC) group (n = 9) and the LV summit group (n = 6) according to the final ablation sites. Measurements with the highest diagnostic performance were modeled into a 4-stepwise algorithm to discriminate LVOT VAs. The performance of this novel algorithm was prospectively tested in a validation cohort of 43 consecutive patients undergoing LVOT VAs ablation. Based on the accuracy of AUC, a 4-stepwise ECG algorithm was developed. First, the QS duration in aVL > 134 ms was used to distinguish VAs from AMC, LV summit and VAs from aortic root (80% sensitivity and 76% specificity). Second, the R duration in II > 155 ms was used to differentiate VAs from LV summit and VAs from AMC (67% sensitivity and 56% specificity). Third, the ratio of III/II < 0.9 was used to discriminate VAs from RCC and VAs from LCC, L-RCC (82% sensitivity and 63% specificity). Fourth, the QS duration of aVR > 130 ms was used to discern VAs from LCC and VAs from L-RCC (75% sensitivity and 62% specificity). In the prospective evaluation, our 4-stepwise ECG algorithm exhibited a good predictive value. We have developed a novel and simple 4-stepwise ECG algorithm with good predictive value to discriminate the AVs from different sites of LVOT.

Transcriptome Profiling Reveals Genes Related to Sex Determination and Differentiation in Sugarcane Borer (Chilo sacchariphagus Bojer).

Chilo sacchariphagus Bojer is an important sugarcane pest globally. Along with genetic modification strategies, the sterile insect technique (SIT) has gained more attention as an environment-friendly method for pest control. The identification of key genes associated with sex determination and differentiation will provide important basic information for this control strategy. As such, the transcriptome sequencing of female and male adults was conducted in order to understand the sex-biased gene expression and molecular basis of sex determination and differentiation in this species. A total of 60,429 unigenes were obtained; among them, 34,847 genes were annotated. Furthermore, 11,121 deferentially expressed genes (DEGs) were identified, of which 8986 were male-biased and 2135 were female-biased genes. The male-biased genes were enriched for carbon metabolism, peptidase activity and transmembrane transport, while the female-biased genes were enriched for the cell cycle, DNA replication, and the MAPK signaling pathway. In addition, 102 genes related to sex-determination and differentiation were identified, including the protein toll, ejaculatory bulb-specific protein, fruitless, transformer-2, sex-lethal, beta-Catenin, sox, gata4, beta-tubulin, cytosol aminopeptidase, seminal fluid, and wnt4. Furthermore, transcription factors such as myb, bhlh and homeobox were also found to be potentially related to sex determination and differentiation in this species. Our data provide new insights into the genetic elements associated with sex determination and differentiation in Chilo sacchariphagus, and identified potential candidate genes to develop pest-control strategies.

Congestive heart failure after extensive catheter ablation for atrial fibrillation: prevalence, characterization, and outcome.

INTRODUCTION: This study sought to describe a new complication of catheter ablation for atrial fibrillation (AF): new onset congestive heart failure (CHF) after extensive ablation for AF. METHODS AND RESULTS: Data from 12 patients developing CHF after ablation were prospectively collected. All patients underwent extensive ablation for AF including circumferential pulmonary venous ablation and complex fractionated atrial electrograms guided ablation. CHF was diagnosed using the following criteria: symptoms or signs of heart failure, elevated BNP, and echocardiographic evidence of left ventricular diastolic dysfunction. Twelve patients (5 persistent and 7 permanent AF) had CHF after extensive ablation out of 484 consecutive AF patients who underwent catheter ablation (prevalence 2.5%). None of these 12 patients had CHF prior to the procedure. The mean onset of the symptoms was 39 ± 14 hours after the index procedure. Dyspnea and pulmonary rales were the most observed symptoms or signs. White blood cell count, serum CRP, BNP, and echocardiographic parameters of left ventricular diastolic dysfunction (E/A, E/E') were significantly increased after the onset of symptoms. All patients had complete recovery with supportive therapy within 3 days of the onset of symptoms. CONCLUSIONS: In this single-center experience, CHF after extensive ablation for AF was a well-recognized complication with a relatively high incidence of 2.5%. Measurement of BNP, CRP, and E/A, E/E' is useful in managing these patients.

Efficacy of catheter ablation and surgical CryoMaze procedure in patients with long-lasting persistent atrial fibrillation and rheumatic heart disease: a randomized trial.

AIMS: Catheter ablation and surgical Maze procedure are effective in treating atrial fibrillation (AF) patients. However, there is no study that compares the effect of circumferential pulmonary vein isolation (CPVI) combined with substrate ablation after valvular surgery and the concomitant Maze procedure for the treatment of AF in patients with rheumatic heart disease (RHD). The aim of this study was to compare the effectiveness of CPVI combined with substrate modification and surgical Maze procedure using Saline-Irrigated Cooled-tip Radiofrequency Ablation (SICTRA) system for the treatment of long-lasting persistent AF in patients with RHD. METHODS AND RESULTS: Between January 2006 and June 2008, 99 patients with long-lasting persistent AF and RHD were randomly assigned to undergo valvular operation and CPVI combined with substrate modification 6 months after the surgery (Group A, 49 patients) or valvualr operation and concomitant Maze procedure (Group B, 50 patients). The mean follow-up periods were 15 ± 5 and 20 ± 8 months in Groups A and B, respectively. After one procedure, Group B had a significantly higher freedom from artial arrhythmias compared with Group A (82% in Group B vs. 55.2% in Group A, P < 0.001). Fifteen patients in Group A underwent a redo procedure. Six patients in Group B underwent catheter ablation and four were treated successfully. The cumulative rates of sinus rhythm were 71% in Group A and 88% in Group B (P < 0.001). CONCLUSION: The concomitant Cox Maze procedure using SICTRA is more effective than subsequent CPVI combined with substrate modification in treating patients with long-lasting persistent AF and RHD.

Impact of corrected sinus node recovery time in predicting recurrence in patients with paroxysmal atrial fibrillation.

OBJECTIVE: Atrial fibrillation (AF) and sinus node dysfunction (SND) have common underlying pathophysiological mechanisms. As an index of SND, corrected sinus node recovery time (CSNRT) may also reflect atrial function. The aim of the present study was to determine whether CSNRT predicts AF recurrence in patients undergoing AF ablation. METHODS: Consecutive patients with paroxysmal atrial fibrillation (PAF) who underwent radiofrequency catheter ablation between January 2017 and December 2018 were enrolled. Clinical data, CSNRT, and other electrophysiology indices were collected and analysed between patients with or without AF recurrence. RESULTS: A total of 159 patients with PAF who underwent the same radiofrequency catheter ablation procedure were enrolled, including 25 patients with SND. During the one-year follow-up period, 22 patients experienced AF recurrence. Patients with recurrence had a significantly longer CSNRT and a larger left atrial volume index (LAVI) than patients without AF recurrence. SND (CSNRT > 550 ms) and a larger LAVI were independently associated with AF recurrence after ablation. A statistically significant CSNRT cut-off value of 550 ms predicted AF recurrence with 73% sensitivity and 85% specificity. CONCLUSION: CSNRT and LAVI are independent predictors of PAF recurrence following ablation.

Overexpression of interleukin-18 aggravates cardiac fibrosis and diastolic dysfunction in fructose-fed rats.

Inflammation plays an important role in the pathophysiology of the metabolic syndrome (MS). We determined whether the overexpression of interleukin (IL)-18 could aggravate left ventricular (LV) remodeling and diastolic dysfunction in fructose-fed rats (FFRs). To create an animal model for MS, male Wistar rats received 10% fructose in water for 8 months. We used an adenovirus encoding rat IL-18 to overexpress IL-18 in FFRs by intravenous administration. IL-18 overexpression led to increases in collagen volume fraction and collagen deposition. LV systolic function was unaltered. But the LV end-diastolic pressure and the time constant of isovolumic relaxation (tau) were increased. Peak negative value of time derivative of LV pressure (-dp/dt) was decreased. Isovolumic relaxation time and myocardial index, as assessed by echocardiography, were increased. Overexpression of IL-18 leads to aggravated LV remodeling and dysfunction in FFRs. Attenuation of the inflammatory process may provide a novel therapeutic strategy in treating metabolic cardiomyopathy.

Novel connexin40 missense mutations in patients with familial atrial fibrillation.

AIMS: This research was aimed at screening connexin40, a cardiac gap junction protein alpha 5, for genetic defects in patients with familial atrial fibrillation (AF). METHODS: The subjects included 218 unrelated families with lone AF and 200 ethnically matched unrelated healthy individuals as controls. The entire coding region of the connexin40 gene was sequenced initially in 218 unrelated probands with familial AF. The relatives of mutation carriers and 200 controls were subsequently genotyped for the presence of mutations identified in probands. RESULTS: Three novel connexin40 mutations, p.V85I, p.L221I, and p.L229M, were identified in 3 of 218 unrelated AF families, respectively. These heterozygous missense mutations co-segregated with AF in the families and were absent in the 200 unrelated control subjects. A cross-species alignment of connexin40 protein sequences revealed that the altered amino acids were completely conserved evolutionarily. CONCLUSION: The findings expand the spectrum of mutations in connexin40 linked to AF and provide new insight into the molecular aetiology involved in the pathogenesis of AF.

The global rise of 3D printing during the COVID-19 pandemic.

3D printing enables on-demand solutions for a wide spectrum of needs ranging from personal protection equipment to medical devices and isolation wards. This versatile technology is suited to address supply-demand imbalances caused by socio-economic trends and disruptions in supply chains.

Decreased connexin 43 and increased fibrosis in atrial regions susceptible to complex fractionated atrial electrograms.

BACKGROUND AND OBJECTIVES: Complex fractionated atrial electrograms (CFAE) is distributed at preferential sites of atrium, and the mechanism underlying CFAE is not fully understood. We hypothesized that preexisting atrial abnormalities may be involved in the formation of CFAE. METHODS: Twelve pigs were subjected to acetylcholine infusion and right atrial pacing to induce sustained atrial fibrillation. The shortest complex interval map was used to visualize CFAE on three-dimensional anatomic structure of left atrium, and the CFAE sites were labeled by ablation. The expression of connexin 43 (Cx43) and myocardial fibrosis were examined. RESULTS: The expression of Cx43 at CFAE sites was significantly decreased when compared with non-CFAE sites, while myocardial fibrosis was enhanced in CFAE sites compared with non-CFAE sites. CONCLUSIONS: These results suggested that the decreased expression of Cx43 and enhanced myocardial fibrosis at CFAE sites of the left atrium may be the structure abnormalities underlying CFAE.