MCU proteins dominate in vivo mitochondrial Ca2+ uptake in Arabidopsis roots.

Ca2+ signaling is central to plant development and acclimation. While Ca2+-responsive proteins have been investigated intensely in plants, only a few Ca2+-permeable channels have been identified, and our understanding of how intracellular Ca2+ fluxes is facilitated remains limited. Arabidopsis thaliana homologs of the mammalian channel-forming mitochondrial calcium uniporter (MCU) protein showed Ca2+ transport activity in vitro. Yet, the evolutionary complexity of MCU proteins, as well as reports about alternative systems and unperturbed mitochondrial Ca2+ uptake in knockout lines of MCU genes, leave critical questions about the in vivo functions of the MCU protein family in plants unanswered. Here, we demonstrate that MCU proteins mediate mitochondrial Ca2+ transport in planta and that this mechanism is the major route for fast Ca2+ uptake. Guided by the subcellular localization, expression, and conservation of MCU proteins, we generated an mcu triple knockout line. Using Ca2+ imaging in living root tips and the stimulation of Ca2+ transients of different amplitudes, we demonstrated that mitochondrial Ca2+ uptake became limiting in the triple mutant. The drastic cell physiological phenotype of impaired subcellular Ca2+ transport coincided with deregulated jasmonic acid-related signaling and thigmomorphogenesis. Our findings establish MCUs as a major mitochondrial Ca2+ entry route in planta and link mitochondrial Ca2+ transport with phytohormone signaling.

LncRNA HCG11/miR-26b-5p/QKI5 feedback loop reversed high glucose-induced proliferation and angiogenesis inhibition of HUVECs.

Acute coronary syndrome caused by the rupture of atherosclerotic plaques is one of the primary causes of cerebrovascular and cardiovascular events. Neovascularization within the plaque is closely associated with its stability. Long non-coding RNA (lncRNA) serves a crucial role in regulating vascular endothelial cells (VECs) proliferation and angiogenesis. In this study, we identified lncRNA HCG11, which is highly expressed in patients with vulnerable plaque compared with stable plaque. Then, functional experiments showed that HCG11 reversed high glucose-induced vascular endothelial injury through increased cell proliferation and tube formation. Meanwhile, vascular-related RNA-binding protein QKI5 was greatly activated. Luciferase reporter assays and RNA-binding protein immunoprecipitation (RIP) assays verified interaction between them. Interestingly, HCG11 can also positively regulated by QKI5. Bioinformatics analysis and luciferase reporter assays showed HCG11 can worked as a competing endogenous RNA by sponging miR-26b-5p, and QKI5 was speculated as the target of miR-26b-5p. Taken together, our findings revered that the feedback loop of lncRNA HCG11/miR-26b-5p/QKI-5 played a vital role in the physiological function of HUVECs, and this also provide a potential target for therapeutic strategies of As.

Preexcitation syndrome: experimental study on the electrocardiogram of antegradely conducting accessory pathway.

BACKGROUND: Preexcitation syndrome is characterized by a dominant delta wave on the baseline electrocardiogram (ECG), resulting from the change in QRS initial vector by the accessory pathway (AP). This study is to explore the effect of ventricular preexcitation on the QRS initial, maximal and terminal vector in an experimental rabbit with preexcitation syndrome induced by programmed electrical stimulation. METHODS: Rabbits (n = 10) were randomized for the experimental model of ventricular preexcitation. Sensing and stimulating electrode catheters were placed in the high right atrium and along epicardial surface of atrioventricular groove of the left ventricular anterior wall, respectively. Programmed premature stimulation S2 was synchronized with P wave and utilized to stimulate the ventricle. The ECG recorded the electrical activity of the heart. As compared with the QRS complex during sinus rhythm, paced QRS was assessed regarding the initial, maximal and terminal vector. PS2 interval and PR interval were also measured and analyzed. RESULTS: Preexcitation was successfully simulated by ventricular pacing in the rabbits, including (1) Complete preexcitation: PS2 interval was less than PR interval; the difference was more than or equal to 47.00 ± 7.53 ms. (2) Incomplete preexcitation: PS2 interval was less than PR interval; the difference was less than 47.00 ± 7.53 ms. (3) Incomplete latent preexcitation: PS2 interval was more than or equal to PR interval; the difference was less than or equal to 13.00 ± 3.50 ms. (4) Complete latent preexcitation: PS2 interval was more than or equal to PR interval; the difference was more than 13.00 ± 3.50 ms. CONCLUSIONS: The difference in the relative conduction velocity of the atrioventricular node versus the AP pathways determines the degree of preexcitation and different manifestation on ECG. The QRS terminal vector also reflects the ventricle preexcitation, indicating a valuable sign for the diagnosis of atypical or latent preexcitation.

Electrocardiogram: his bundle potentials can be recorded noninvasively beat by beat on surface electrocardiogram.

BACKGROUND: The micro waveform of His bundle potential can't be recorded beat-to-beat on surface electrocardiogram yet. We have found that the micro-wavelets before QRS complex may be related to atrioventricular conduction system potentials. This study is to explore the possibility of His bundle potential can be noninvasively recorded on surface electrocardiogram. METHODS: We randomized 65 patients undergoing radiofrequency catheter ablation of paroxysmal superventricular tachycardia (exclude overt Wolff-Parkinson-White syndrome) to receive "conventional electrocardiogram" and "new electrocardiogram" before the procedure. His bundle electrogram was collected during the procedure. Comparative analysis of PAs (PA interval recorded on surface electrocardiogram), AHs (AH interval recorded on surface electrocardiogram) and HVs (HV interval recorded on surface electrocardiogram) interval recorded on surface "new electrocardiogram" and PA, AH, HV interval recorded on His bundle electrogram was investigated. RESULTS: There was no difference (P > 0.05) between groups in HVs interval (49.63 ± 6.19 ms) and HV interval (49.35 ± 6.49 ms). Results of correlational analysis found that HVS interval was significantly positively associated with HV interval (r = 0.929; P < 0.01). CONCLUSIONS: His bundle potentials can be noninvasively recorded on surface electrocardiogram. Noninvasive His bundle potential tracing might represent a new method for locating the site of atrioventricular block and identifying the origin of a wide QRS complex.

Effects of Antegrade Accessory Pathway Conduction on QRS Terminal Vector in Patients with Preexcitation Syndrome.

BACKGROUND: Ventricle preexcitation through accessory pathway changes QRS initial vector, and manifests as delta wave on electrocardiogram (ECG). However, QRS terminal vector can also be affected. METHODS: A total of 158 patients who had single accessory pathway (AP) with antegrade conduction capacity were included and divided into two groups according to the ECG with or without delta wave. Note that 150 patients had delta wave (overt AP group) on ECG; classical preexcitation syndrome was diagnosed before radiofrequency ablation. Eight patients had no delta wave on ECG (unapparent AP group); preexcitation was induced by transesophageal atrial pacing. ECGs and intracardiac electrogram (IEGM) before and after ablation and during atrioventricular reentrant tachycardia were analyzed. RESULTS: (1) In the overt AP group: QRS terminal vector amplitude and polarity changes were observed in all the 150 patients, and were related to AP location and delta wave polarity. (2) In the unapparent AP group: QRS terminal vector changes were found in two out of eight patients, and the initial activation of ventricle myocardium via AP on IEGM was almost simultaneous with the onset of QRS complex on ECG. CONCLUSIONS: It is not only the QRS initial vector, but also the QRS terminal vector that can be changed by the antegrade accessory pathway conduction in patients with preexcitation syndrome. The change of QRS terminal vector is valuable for the diagnosis of atypical preexcitation.

Association of peroxisome proliferator-activated receptor delta and additional gene-smoking interaction on cardiovascular disease.

AIMS: To investigate the impact of peroxisome proliferator-activator receptor delta (PPARD) gene polymorphism and additional gene-smoking interaction on cardiovascular disease (CVD) risk based on this Chinese population. METHODS: A total of 1048 subjects (617 males, 431 females) with a mean age of 52.9 ± 14.1 years old were selected, including 520 CVD patients and 528 normal control subjects. The logistic regression model was used to examine the association between three SNPs and CVD risk, odds ratio (OR), and 95% confident interval (95%CI) were calculated. Generalized multifactor dimensionality reduction (GMDR) was employed to investigate the gene-smoking interaction. RESULTS: Genotypes of variants in rs2016520 and rs9794 were associated with decreased CVD risk, and CVD risk was significantly lower in carriers of C allele of the rs2016520 polymorphism than those with the TT genotype (TC+CC versus TT), adjusted OR (95%CI) = 0.71 (0.56-0.86). In addition, we also found that CVD risk was also significantly lower in carriers of the G allele of the rs9794 polymorphism than those with the CC genotype (CG+ GG versus CC), adjusted OR (95%CI) = 0.69 (0.53-0.86). GMDR analysis suggested a potential gene-environment interaction between rs2016520 and smoking. Overall, the two-locus models had a cross-validation consistency of 10 of 10, and had the testing accuracy of 62.17%, and never smokers with TC or CC of the rs2016520 genotype have the lowest CVD risk, compared to smokers with TT of rs2016520, OR (95%CI) was 0.42 (0.23-0.66). CONCLUSIONS: The minor allele of rs2016520 and rs9794 in PPAR-δ and interaction between rs2016520 and non-smoking were associated with decreased risk of CVD.

Transport of Calcium Ions into Mitochondria.

To uptake calcium ions of mitochondria is of significant functional connotation for cells, because calcium ions in mitochondria are involved in energy production, regulatory signals transfer, and mitochondrial permeability transition pore opening and even programmed cell death of apoptosis, further playing more roles in plant productivity and quality. Cytoplasmic calcium ions access into outer mitochondrial membrane (OMM) from voltage dependent anion-selective channel (VDAC) and were absorbed into inner mitochondrial membrane (IMM) by mitochondrial calcium uniporter (MCU), rapid mitochondrial calcium uptake (RaM) or mitochondrial ryanodine receptor (mRyR). Although both mitochondria and the mechanisms of calcium transport have been extensively studied, but there are still long-standing or even new challenges. Here we review the history and recent discoveries of the mitochondria calcium ions channel complex involved calcium assimilation, and discuss the role of calcium ions into mitochondria.

Overexpression of GmERF5, a new member of the soybean EAR motif-containing ERF transcription factor, enhances resistance to Phytophthora sojae in soybean.

Phytophthora root and stem rot of soybean [Glycine max (L.) Merr.], caused by Phytophthora sojae Kaufmann and Gerdemann, is a destructive disease throughout the soybean planting regions in the world. Here, we report insights into the function and underlying mechanisms of a novel ethylene response factor (ERF) in soybean, namely GmERF5, in host responses to P. sojae. GmERF5-overexpressing transgenic soybean exhibited significantly enhanced resistance to P. sojae and positively regulated the expression of the PR10, PR1-1, and PR10-1 genes. Sequence analysis suggested that GmERF5 contains an AP2/ERF domain of 58 aa and a conserved ERF-associated amphiphilic repression (EAR) motif in its C-terminal region. Following stress treatments, GmERF5 was significantly induced by P. sojae, ethylene (ET), abscisic acid (ABA), and salicylic acid (SA). The activity of the GmERF5 promoter (GmERF5P) was upregulated in tobacco leaves with ET, ABA, Phytophthora nicotianae, salt, and drought treatments, suggesting that GmERF5 could be involved not only in the induced defence response but also in the ABA-mediated pathway of salt and drought tolerance. GmERF5 could bind to the GCC-box element and act as a repressor of gene transcription. It was targeted to the nucleus when transiently expressed in Arabidopsis protoplasts. GmERF5 interacted with a basic helix-loop-helix transcription factor (GmbHLH) and eukaryotic translation initiation factor (GmEIF) both in yeast cells and in planta. To the best of our knowledge, GmERF5 is the first soybean EAR motif-containing ERF transcription factor demonstrated to be involved in the response to pathogen infection.

Very early recurrence of Takotsubo syndrome.

An 82-year-old female presented lasting chest pain for stimulation and the ECG revealed ventricular fibrillation and ST segment elevation, so we considered acute myocardial infarction. However, after the clinical condition of the patient improved, symptoms recurred for stimulation again on day 4. An echocardiogram showed left ventricular apical ballooning, so, we diagnosed her as Takotsubo syndrome.

Two new cytochalasins from the endophytic fungus Xylaria sp. GDGJ-77B.

Two new open-chain cytochalasins, xylarchalasins A and B (1 and 2), together with six known analogues (3-8), were isolated from the endophytic fungus Xylaria sp. GDGJ-77B from the Chinese medicinal plant Sophora tonkinensis. Their structures were elucidated on the basis of comprehensive spectroscopic analysis. Compound 2 displayed moderate antibacterial activities against Bacillus subtilis and Escherichia coli with MIC values of 25 and 12.5 µg/mL, respectively.

Efficacy of angiotensin receptor neprilysin inhibitor in Asian patients with refractory hypertension.

Sacubitril/valsartan, simultaneously inhibits neprilysin and angiotensin II receptor, showed an effect in reducing blood pressure (BP). The authors aimed to study whether it can be used as an antihypertensive agent in patients with refractory hypertension who have already been treated. A total of 66 Chinese patients with refractory hypertension were enrolled. Patients received sacubitril/valsartan  200 instead of angiotensin II receptor blocker or angiotensin converting enzyme inhibitor while other agents continued. If BP was uncontrolled after 4 weeks, sacubitril/valsartan was increased to 400 mg. The BP reduction was evaluated by office BP and ambulatory BP monitoring after 8-week treatment. The baseline office BP and mean arterial pressure (MAP) were 150.0/95.0 mmHg and 113.3 mmHg. BP and MAP reduced to 130.6/83.2 mmHg and 99.0 mmHg at week 8. Office BP and MAP reductions were 19.4/11.8 mmHg and 14.3 mmHg at endpoint (all p < .001). The 24-h, daytime and nighttime ambulatory BP were 146.2/89.1, 148.1/90.3, and 137.5/83.7 mmHg, respectively at baseline, and BP reduced to 129.6/79.8, 130.6/81.1, and 121.7/75.8 mmHg, respectively at week 8. The 24-h, daytime and nighttime ambulatory BP reductions were 16.6/9.3, 17.5/9.2, and 15.8/7.9 mmHg, respectively at endpoint (all p < .001). Sacubitril/valsartan significantly reduced office and ambulatory BP in refractory hypertension patients. Our study provided new evidence for sacubitril/valsartan in refractory hypertension.

Three new andrastin derivatives from the endophytic fungus Penicillium vulpinum.

Three new andrastin derivatives, 10-formyl andrastone A (1), 10-demethylated andrastone A (2) and andrastin G (3), together with four known andrastin analogues (4-7) were isolated from an endophytic fungus Penicillium vulpinum. Their structures were determined by 1 D, 2 D NMR, and the absolute configurations were further determined by experimental and calculated ECD spectra. Compound 5 exhibited significant antibacterial activity against Bacillus paratyphosus B with an MIC value of 6.25 µg·mL-1. Compounds 2 and 6 showed remarkable inhibitory activities against Bacillus megaterium with the MIC value of 6.25 µg·mL-1, respectively.

Two new phthalide derivatives from the endophytic fungus Penicillium vulpinum isolated from Sophora tonkinensis.

Two new phthalide derivatives, (-)-3-carboxypropyl-7-hydroxyphthalide (1) and (-)-3-carboxypropyl-7-hydroxyphthalide methyl ester (2), were isolated from the endophytic fungus Penicillium vulpinum isolated from the Chinese medicinal plant Sophora tonkinensis. Their structures were elucidated using spectroscopic methods, mainly on 1D and 2D NMR. Compound 1 exhibited medium antibacterial activities against Bacillus subtilis, Shigella dysenteriae and Enterobacter areogenes with MIC values of 12.5-25 µg/mL, and 2 showed a medium inhibition to E. areogenes with MIC value of 12.5 µg/mL.

Cytochalasins from endophytic Diaporthe sp. GDG-118.

The plant Sophora tonkinensis, possessed a range of active compounds, was traditionally used in the medicine of Chinese minorities. Endophytic fungi were isolated from this plant, of which the fungus Diaporthe sp. GDG-118 was fermented and extracted with methanol. The extract was screened by antifungal and antibacterial assays leading to the discovery of two new 21-acetoxycytochalasins (1-2) and five known cytochalasins (3-7). These two new compounds were elucidated by spectroscopic analyses, and further their absolute configurations were determined by the X-ray of compound 3 and comparing their experimental CD spectra. The antibacterial and antifungal effects of these compounds were evaluated. Compound 2 showed significant inhibitory activity against Bacillus anthraci and Escherichia coli with MIC value of 12.5 µg/mL, and 7 showed strong antifungal activity against Alternaria oleracea, Pestalotiopsis theae and Colletotrichum capsici with MIC values of 3.125, 1.56 and 1.56 µg/mL, respectively.

Author Correction: Genome-wide identification of Major Intrinsic Proteins in Glycine soja and characterization of GmTIP2;1 function under salt and water stress.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Unusual Tachycardia in a Patient With Chest Pain and Bradycardia.

This case report describes a patient in their 50s who presented with squeezing chest pain for 4 hours and an initial electrocardiogram showing acute inferior wall and right ventricular infarction with third-degree atrioventricular block.

[Prograde conduction of the pathway in pre-excitation syndrome may shorten PJ interval].

OBJECTIVE: To investigate whether the PJ interval in the patients with pre-excitation syndrome can be shortened by pathway conduction, and to explore the clinical implications of the prolonged PJ interval. METHODS: 143 patients with single pathway, who experienced successful radiofrequency (RF) ablation, were divided into two groups: Group A (n = 132) with normal atrioventricular and ventricular conduction (sub-divided into 10 subsets further according to the location of the pathway) and Group B (n = 11) with first degree atrioventricular block or with bundle branch block. The ECG images with and without pathway conduction were analyzed. RESULTS: (1) The PJ interval in the patients with right posterior pathway or with right septal pathway was shortened significantly after the RF [(226 +/- 18) ms vs (236 +/- 19) ms and (221 +/- 18) ms vs (238 +/- 31) ms respectively, both P < 0.05 ]; (2) The PJ interval in Group B was shortened to different extents. The PJ interval values in 4 patients with first degree atrioventricular block were shortened, but still beyond normal extent. The PJ interval values in 4 patients with bundle branch block were shortened to normal extent. CONCLUSION: If the pre-excitation syndrome patients have normal atrioventricular conduction the PJ interval is normal or the PJ interval may be shortened. If the patients have prolonged atrioventricular conduction, the PJ interval may be shortened by the pathway prograde conduction. PJ interval prolongation indicates atrioventricular conduction delay or ventricular conduction block, but bundle branch block cannot be excluded when the PJ interval is normal.