Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins.

The current outbreak of coronavirus disease-2019 (COVID-19) poses unprecedented challenges to global health1. The new coronavirus responsible for this outbreak-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-shares high sequence identity to SARS-CoV and a bat coronavirus, RaTG132. Although bats may be the reservoir host for a variety of coronaviruses3,4, it remains unknown whether SARS-CoV-2 has additional host species. Here we show that a coronavirus, which we name pangolin-CoV, isolated from a Malayan pangolin has 100%, 98.6%, 97.8% and 90.7% amino acid identity with SARS-CoV-2 in the E, M, N and S proteins, respectively. In particular, the receptor-binding domain of the S protein of pangolin-CoV is almost identical to that of SARS-CoV-2, with one difference in a noncritical amino acid. Our comparative genomic analysis suggests that SARS-CoV-2 may have originated in the recombination of a virus similar to pangolin-CoV with one similar to RaTG13. Pangolin-CoV was detected in 17 out of the 25 Malayan pangolins that we analysed. Infected pangolins showed clinical signs and histological changes, and circulating antibodies against pangolin-CoV reacted with the S protein of SARS-CoV-2. The isolation of a coronavirus from pangolins that is closely related to SARS-CoV-2 suggests that these animals have the potential to act as an intermediate host of SARS-CoV-2. This newly identified coronavirus from pangolins-the most-trafficked mammal in the illegal wildlife trade-could represent a future threat to public health if wildlife trade is not effectively controlled.

Pathogenicity, tissue tropism and potential vertical transmission of SARSr-CoV-2 in Malayan pangolins.

Malayan pangolin SARS-CoV-2-related coronavirus (SARSr-CoV-2) is closely related to SARS-CoV-2. However, little is known about its pathogenicity in pangolins. Using CT scans we show that SARSr-CoV-2 positive Malayan pangolins are characterized by bilateral ground-glass opacities in lungs in a similar manner to COVID-19 patients. Histological examination and blood gas tests are indicative of dyspnea. SARSr-CoV-2 infected multiple organs in pangolins, with the lungs the major target, and histological expression data revealed that ACE2 and TMPRSS2 were co-expressed with viral RNA. Transcriptome analysis indicated that virus-positive pangolins were likely to have inadequate interferon responses, with relative greater cytokine and chemokine activity in the lung and spleen. Notably, both viral RNA and viral proteins were detected in three pangolin fetuses, providing initial evidence for vertical virus transmission. In sum, our study outlines the biological framework of SARSr-CoV-2 in pangolins, revealing striking similarities to COVID-19 in humans.

Scale Invariance of a Spherical Unitary Fermi Gas.

A unitary Fermi gas in an isotropic harmonic trap is predicted to show scale and conformal symmetry that have important consequences in its thermodynamic and dynamical properties. By experimentally realizing a unitary Fermi gas in an isotropic harmonic trap, we demonstrate its universal expansion dynamics along each direction and at different temperatures. We show that as a consequence of SO(2,1) symmetry, the measured release energy is equal to that of the trapping energy. We further observe the breathing mode with an oscillation frequency twice the trapping frequency and a small damping rate, providing the evidence of SO(2,1) symmetry. In addition, away from resonance when scale invariance is broken, we determine the effective exponent γ that relates the chemical potential and average density along the BEC-BCS crossover, which qualitatively agrees with the mean field predictions. This Letter opens the possibility of studying nonequilibrium dynamics in a conformal invariant system in the future.

Effect of different screen brightness and devices on online visual acuity test.

PURPOSE: This study aimed to study the difference in test results of online visual acuity (VA) test under different devices and screen brightness conditions and to compare online VA test with Early Treatment Diabetic Retinopathy Study (ETDRS). METHODS: Healthy volunteers with the best corrected VA of 0.0 LogMAR or higher were recruited. VAs under ETDRS were tested first, and then online VA test (the Stanford Acuity Test, StAT) visual acuities using iPad Air2 and Microsoft Surface pro4 under 50% and 100% screen brightness were performed. The VA results and the testing times were compared between different devices and screen brightness conditions. RESULTS: A total of 101 eyes were included in this study. The VA results measured by the StAT were better than those of ETDRS. The VA results measured at 100% screen brightness were better than those of 50% brightness (mean difference, 0.013 logMAR at most, less than 1 letter); the VA results measured by iPad Air2 were better than those of Surface pro4 (mean difference, -0.009 logMAR at most, less than 1 letter). Significantly less time was spent on VA testing under StAT than that under ETDRS. CONCLUSION: The impact of screen brightness and the device on the VA results generated by online VA tests was clinically insignificant. In addition, online VA tests are found to be reliable and more time efficient than ETDRS.

Population genomic analysis provides evidence of the past success and future potential of South China tiger captive conservation.

BACKGROUND: Among six extant tiger subspecies, the South China tiger (Panthera tigris amoyensis) once was widely distributed but is now the rarest one and extinct in the wild. All living South China tigers are descendants of only two male and four female wild-caught tigers and they survive solely in zoos after 60 years of effective conservation efforts. Inbreeding depression and hybridization with other tiger subspecies were believed to have occurred within the small, captive South China tiger population. It is therefore urgently needed to examine the genomic landscape of existing genetic variation among the South China tigers. RESULTS: In this study, we assembled a high-quality chromosome-level genome using long-read sequences and re-sequenced 29 high-depth genomes of the South China tigers. By combining and comparing our data with the other 40 genomes of six tiger subspecies, we identified two significantly differentiated genomic lineages among the South China tigers, which harbored some rare genetic variants introgressed from other tiger subspecies and thus maintained a moderate genetic diversity. We noticed that the South China tiger had higher FROH values for longer runs of homozygosity (ROH > 1 Mb), an indication of recent inbreeding/founder events. We also observed that the South China tiger had the least frequent homozygous genotypes of both high- and moderate-impact deleterious mutations, and lower mutation loads than both Amur and Sumatran tigers. Altogether, our analyses indicated an effective genetic purging of deleterious mutations in homozygous states from the South China tiger, following its population contraction with a controlled increase in inbreeding based on its pedigree records. CONCLUSIONS: The identification of two unique founder/genomic lineages coupled with active genetic purging of deleterious mutations in homozygous states and the genomic resources generated in our study pave the way for a genomics-informed conservation, following the real-time monitoring and rational exchange of reproductive South China tigers among zoos.

Dysfunction of AMPA receptor GluA3 is associated with aggressive behavior in human.

Inappropriate aggression in humans hurts the society, families and individuals. The genetic basis for aggressive behavior, however, remains largely elusive. In this study, we identified two rare missense variants in X-linked GRIA3 from male patients who showed syndromes featuring aggressive outbursts. Both G630R and E787G mutations in AMPA receptor GluA3 completely lost their ion channel functions. Furthermore, a guanine-repeat single nucleotide polymorphism (SNP, rs3216834) located in the first intron of human GRIA3 gene was found to regulate GluA3 expression with longer guanine repeats (rs3216834-10G/-11G) suppressing transcription compared to the shorter ones (-7G/-8G/-9G). Importantly, the distribution of rs3216834-10G/-11G was elevated in a male violent criminal sample from Chinese Han population. Using GluA3 knockout mice, we showed that the excitatory neurotransmission and neuronal activity in the medial prefrontal cortex (mPFC) was impaired. Expressing GluA3 back into the mPFC alleviated the aggressive behavior of GluA3 knockout mice, suggesting that the defects in mPFC explained, at least partially, the neural mechanisms underlying the aggressive behavior. Therefore, our study provides compelling evidence that dysfunction of AMPA receptor GluA3 promotes aggressive behavior.

Puerarin Protects against Myocardial Ischemia/Reperfusion Injury by Inhibiting Ferroptosis.

This study investigated whether pretreatment with puerarin could alleviate myocardial ischemia/reperfusion (I/R) injury in a cardiomyocyte oxygen-glucose deprivation and reoxygenation (OGD/R) model and in a mouse I/R injury model. For in vitro experiments, H9C2 cells were divided into control, erastin, OGD/R, OGD/R + puerarin, and OGD/R + ferrostatin (Fer)-1 groups. Parameters related to ferroptosis included levels of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), ATP, reactive oxygen species (ROS), glutathione (GSH), prostaglandin endoperoxide synthase (Ptgs) 2 mRNA, glutathione peroxidase (GPX) 4 protein and iron. In H9C2 cells, puerarin or Fer-1 pretreatment reduced ferroptosis, as indicated by decreased ROS and increased GSH, ATP levels. In vivo, wild-type mice were randomly divided into sham, I/R + vehicle, I/R + puerarin, and IR + Fer-1 groups. The I/R model was established by 30 min of left anterior descending artery occlusion followed by 24 h of reperfusion. Pretreatment with puerarin or Fer-1 significantly reduced infarct size in I/R mice, and decreased the activities of Myeloperoxidase (MPO) and cardiac enzymes such as creatine kinase MB isoenzyme (CK-MB), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) compared to those in the vehicle-treated group. Puerarin also reduced the production of MDA and 4-HNE, reduced the mRNA expression of Ptgs2 mRNA, and increased GPX4 protein expression. These results showed that puerarin exerted protective effects against myocardial I/R injury by inhibiting ferroptosis and inflammation, and therefore may have therapeutic potential for treatment of acute myocardial infarction.

Targeting presynaptic H3 heteroreceptor in nucleus accumbens to improve anxiety and obsessive-compulsive-like behaviors.

Anxiety commonly co-occurs with obsessive-compulsive disorder (OCD). Both of them are closely related to stress. However, the shared neurobiological substrates and therapeutic targets remain unclear. Here we report an amelioration of both anxiety and OCD via the histamine presynaptic H3 heteroreceptor on glutamatergic afferent terminals from the prelimbic prefrontal cortex (PrL) to the nucleus accumbens (NAc) core, a vital node in the limbic loop. The NAc core receives direct hypothalamic histaminergic projections, and optogenetic activation of hypothalamic NAc core histaminergic afferents selectively suppresses glutamatergic rather than GABAergic synaptic transmission in the NAc core via the H3 receptor and thus produces an anxiolytic effect and improves anxiety- and obsessive-compulsive-like behaviors induced by restraint stress. Although the H3 receptor is expressed in glutamatergic afferent terminals from the PrL, basolateral amygdala (BLA), and ventral hippocampus (vHipp), rather than the thalamus, only the PrL- and not BLA- and vHipp-NAc core glutamatergic pathways among the glutamatergic afferent inputs to the NAc core is responsible for co-occurrence of anxiety- and obsessive-compulsive-like behaviors. Furthermore, activation of the H3 receptor ameliorates anxiety and obsessive-compulsive-like behaviors induced by optogenetic excitation of the PrL-NAc glutamatergic afferents. These results demonstrate a common mechanism regulating anxiety- and obsessive-compulsive-like behaviors and provide insight into the clinical treatment strategy for OCD with comorbid anxiety by targeting the histamine H3 receptor in the NAc core.

[Network Meta-analysis of Chinese medicine injections for activating blood and resolving stasis in adjuvant treatment of acute ischemic stroke].

Network Meta-analysis was employed to compare the efficacy of Chinese medicine injections for activating blood and resolving stasis combined with conventional western medicine in the treatment of acute ischemic stroke and the effects on platelet aggregation rate, fibrinogen(FIB), and hypersensitive C-reactive protein(hs-CRP), with a view to providing evidence-based medicine reference for clinical medication. CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, Cochrane Library, and EMbase were searched for randomized controlled trial(RCT) on the treatment of acute ischemic stroke with Salvia Miltiorrhiza Ligustrazine Injection, Danhong Injection, Shuxuetong Injection, Xueshuantong Injection, Shuxuening Injection, Safflower Yellow Pigment Injection, and Ginkgo Diterpene Lactone Meglumine Injection combined with conventional western medicine. The retrieval time was from database inception to March 18, 2023. The articles were extracted by two researchers and their quality was evaluated. R 4.2.2 was used for network Meta-analysis. A total of 87 RCTs involving 8 580 patients were included. Network Meta-analysis showed that, in terms of reducing National Institutes of Health stroke scale(NIHSS) scores, the surface under the cumulative ranking curve(SUCRA) showed the order of Xueshuantong Injection + conventional western medicine(88.7%) > Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine(73.7%) > Shuxuetong Injection + conventional western medicine(69.7%) > Shuxuening Injection + conventional western medicine(51.8%) > Danhong Injection + conventional western medicine(43.7%) > Safflower Yellow Pigment Injection + conventional western medicine(36.8%) > Ginkgo Diterpene Lactone Meglumine Injection + conventional western medicine(35.3%) > conventional western medicine(1.7%). In terms of improving clinical total effective rate, SUCRA showed the order of Danhong Injection + conventional western medicine(63.0%) > Shuxuening Injection + conventional western medicine(59.0%) > Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine(58.9%) > Safflower Yellow Pigment Injection + conventional western medicine(57.1%) > Xueshuantong Injection + conventional western medicine(56.8%) > Shuxuetong Injection + conventional western medicine(54.6%) > Ginkgo Diterpene Lactone Meglumine Injection + conventional western medicine(50.5%) > conventional western medicine(0.03%). In terms of improving Barthel index, SUCRA showed the order of Danhong Injection + conventional western medicine(84.7%) > Shuxuetong Injection + conventional western medicine(72.4%) > Safflower Yellow Pigment Injection + conventional western medicine(61.6%) > Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine(44.6%) > Ginkgo Diterpene Lactone Meglumine Injection + conventional western medicine(43.2%) > Shuxuening Injection + conventional western medicine(42.2%) > conventional western medicine(1.4%). In terms of reducing platelet aggregation rate, SUCRA showed the order of Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine(82.4%) > Shuxuetong Injection + conventional western medicine(81.6%) > Ginkgo Diterpene Lactone Meglumine Injection + conventional western medicine(40.7%) > Danhong Injection + conventional western medicine(37.3%) > conventional western medicine(8.0%). In terms of reducing FIB, SUCRA showed the order of Danhong Injection + conventional western medicine(81.0%) > Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine(71.9%) > Ginkgo Diterpene Lactone Meglumine Injection + conventional western medicine(70.0%) > Shuxuetong Injection + conventional western medicine(46.7%) > Xueshuantong Injection + conventional western medicine(22.6%) > conventional western medicine(8.7%). In terms of reducing hs-CRP, SUCRA showed the order of Shuxuening Injection + conventional western medicine(89.9%) > Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine(78.8%) > Ginkgo Diterpene Lactone Meglumine Injection + conventional western medicine(52.4%) > Danhong Injection + conventional western medicine(47.6%) > Xueshuantong Injection + conventional western medicine(43.5%) > Shuxuetong Injection + conventional Western medicine(35.6%) > conventional western medicine(2.3%). The results indicated that Xueshuantong Injection + conventional western medicine, Danhong Injection + conventional western medicine, and Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine ranked the top three. Xueshuantong Injection + conventional western medicine had the best effect on reducing NIHSS scores. Danhong Injection + conventional western medicine showed the best performance of improving clinical total effective rate, improving Barthel index, and reducing FIB in the blood. Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine had the best effect on reducing platelet aggregation rate in the blood. Shuxuening Injection + conventional western medicine had the best effect on reducing hs-CRP. However, more high-quality RCTs are needed for verification in the future to provide more reliable evidence-based medical reference.

Triglyceride-glucose index and the risk of heart failure: Evidence from two large cohorts and a mendelian randomization analysis.

BACKGROUND: The relationship between triglyceride-glucose (TyG) index, an emerging marker of insulin resistance, and the risk of incident heart failure (HF) was unclear. This study thus aimed to investigate this relationship. METHODS: Subjects without prevalent cardiovascular diseases from the prospective Kailuan cohort (recruited during 2006-2007) and a retrospective cohort of family medicine patients from Hong Kong (recruited during 2000-2003) were followed up until December 31st, 2019 for the outcome of incident HF. Separate adjusted hazard ratios (aHRs) summarizing the relationship between TyG index and HF risk in the two cohorts were combined using a random-effect meta-analysis. Additionally, a two-sample Mendelian randomization (MR) of published genome-wide association study data was performed to assess the causality of observed associations. RESULTS: In total, 95,996 and 19,345 subjects from the Kailuan and Hong Kong cohorts were analyzed, respectively, with 2,726 cases of incident HF in the former and 1,709 in the latter. Subjects in the highest quartile of TyG index had the highest risk of incident HF in both cohorts (Kailuan: aHR 1.23 (95% confidence interval: 1.09-1.39), PTrend <0.001; Hong Kong: aHR 1.21 (1.04-1.40), PTrend =0.007; both compared with the lowest quartile). Meta-analysis showed similar results (highest versus lowest quartile: HR 1.22 (1.11-1.34), P < 0.001). Findings from MR analysis, which included 47,309 cases and 930,014 controls, supported a causal relationship between higher TyG index and increased risk of HF (odds ratio 1.27 (1.15-1.40), P < 0.001). CONCLUSION: A higher TyG index is an independent and causal risk factor for incident HF in the general population. CLINICAL TRIAL REGISTRATION: URL: https://www.chictr.org.cn ; Unique identifier: ChiCTR-TNRC-11,001,489.

Predictable maternal separation confers adult stress resilience via the medial prefrontal cortex oxytocin signaling pathway in rats.

Early-life stress is normally thought of as a major risk for psychiatric disorders, but many researchers have revealed that adversity early in life may enhance stress resilience later in life. Few studies have been performed in rodents to address the possibility that exposure to early-life stress may enhance stress resilience, and the underlying neural mechanisms are far from being understood. Here, we established a "two-hit" stress model in rats by applying two different early-life stress paradigms: predictable and unpredictable maternal separation (MS). Predictable MS during the postnatal period promotes resilience to adult restraint stress, while unpredictable MS increases stress susceptibility. We demonstrate that structural and functional impairments occur in glutamatergic synapses in pyramidal neurons of the medial prefrontal cortex (mPFC) in rats with unpredictable MS but not in rats with predictable MS. Then, we used differentially expressed gene (DEG) analysis of RNA sequencing data from the adult male PFC to identify a hub gene that is responsible for stress resilience. Oxytocin, a peptide hormone, was the highest ranked differentially expressed gene of these altered genes. Predictable MS increases the expression of oxytocin in the mPFC compared to normal raised and unpredictable MS rats. Conditional knockout of the oxytocin receptor in the mPFC was sufficient to generate excitatory synaptic dysfunction and anxiety behavior in rats with predictable MS, whereas restoration of oxytocin receptor expression in the mPFC modified excitatory synaptic function and anxiety behavior in rats subjected to unpredictable MS. These findings were further supported by the demonstration that blocking oxytocinergic projections from the paraventricular nucleus of the hypothalamus (PVN) to the mPFC was sufficient to exacerbate anxiety behavior in rats exposed to predictable MS. Our findings provide direct evidence for the notion that predictable MS promotes stress resilience, while unpredictable MS increases stress susceptibility via mPFC oxytocin signaling in rats.

Reduced motor cortex GABABR function following chronic alcohol exposure.

The GABAB receptor (GABABR) agonist baclofen has been used to treat alcohol and several other substance use disorders (AUD/SUD), yet its underlying neural mechanism remains unclear. The present study aimed to investigate cortical GABABR dynamics following chronic alcohol exposure. Ex vivo brain slice recordings from mice chronically exposed to alcohol revealed a reduction in GABABR-mediated currents, as well as a decrease of GABAB1/2R and G-protein-coupled inwardly rectifying potassium channel 2 (GIRK2) activities in the motor cortex. Moreover, our data indicated that these alterations could be attributed to dephosphorylation at the site of serine 783 (ser-783) in GABAB2 subunit, which regulates the surface expression of GABABR. Furthermore, a human study using paired-pulse-transcranial magnetic stimulation (TMS) analysis further demonstrated a reduced cortical inhibition mediated by GABABR in patients with AUD. Our findings provide the first evidence that chronic alcohol exposure is associated with significantly impaired cortical GABABR function. The ability to promote GABABR signaling may account for the therapeutic efficacy of baclofen in AUD.

Comparisons of electrophysiological characteristics, pacing parameters and mid- to long-term effects in right ventricular septal pacing, right ventricular apical pacing and left bundle branch area pacing.

BACKGROUND: As a near-physiological pacing innovation, left bundle branch area pacing (LBBAP) has drawn much attention recently. This study was aimed to investigate the electrophysiological characteristics, unipolar/bipolar pacing parameters and mid- to long-term effects and safety of three different pacing methods and identify possible predictors of adverse left ventricular remodeling. METHODS: Ninety-two patients were divided into the LBBAP group, right ventricular septal pacing (RVSP) group and right ventricular apical pacing (RVAP) group. Baseline information, electrophysiological, pacing and echocardiographic parameters were collected. RESULTS: The three pacing methods were performed with a similar high success rate. The paced QRSd was significantly different among the LBBAP, RVSP and RVAP groups (105.93 ± 15.85 ms vs. 143.63 ± 14.71 ms vs. 155.39 ± 14.17 ms, p < 0.01). The stimulus to left ventricular activation time (Sti-LVAT) was the shortest in the LBBAP group, followed by the RVSP and RVAP groups (72.80 ± 12.07 ms vs. 86.29 ± 8.71 ms vs. 94.14 ± 10.14 ms, p < 0.001). LBBAP had a significantly lower tip impedance during the procedure and 3-month follow up as compared to RVSP and RVAP (p < 0.001). Higher bipolar captured thresholds were observed in LBBAP during the procedure (p < 0.001). Compared to the baseline values, there was a greater reduction in left ventricular end-diastolic dimension (LVEDD) in the LBBAP group (p = 0.046) and a significant enlargement in LVEDD in the RVAP group (p = 0.008). Multiple regression analysis revealed that the Sti-LVAT was a significant predictor of LVEDD at 12 months post-procedure. At the 24-h post-procedure, significant elevations were observed in the cTnI levels in LBBAP (p < 0.001) and RVSP (p < 0.05). More transient RBB injury was observed in LBBAP. But no significant difference was found in cardiac composite endpoints among three groups (p > 0.05). CONCLUSIONS: LBBAP demonstrated a stable captured threshold, a low tip impedance and a high R-wave amplitude during the 12-month follow-up. Left ventricular remodeling was improved at 12 months post-procedure through LBBAP. The Sti-LVAT was a significant predictor of left ventricular remodeling. LBBAP demonstrated its feasibility, effectiveness, safety and some beneficial electrophysiological characteristics during this mid- to long-term follow-up, which should be confirmed by further studies.

C-reactive protein and atrial fibrillation: Insights from epidemiological and Mendelian randomization studies.

BACKGROUND AND AIMS: This study aimed to investigate the role of C-reactive protein (CRP) in atrial fibrillation (AF) from epidemiological and genetic perspectives. METHODS AND RESULTS: Individual-level data from the Kailuan cohort recruited between 2006 and 2017 were included. Serum CRP levels were measured at baseline and at biennial follow-up visits, and incident AF was ascertained from biennial 12-lead ECG assessment and medical records. Cox proportional hazards models were used to assess the association between baseline CRP levels or cumulative exposure to CRP and incident AF. A meta-analysis including nine prospective cohort studies and our current study was also conducted. Mendelian randomization (MR) analysis was performed to evaluate the aetiological role of CRP in AF. In our observational study (n = 86,424), high baseline CRP levels (>3 mg/L), compared with low CRP (<1 mg/L), were not significantly associated with AF risk (HR: 1.18; 95% CI: 0.99-1.40). High cumulative exposure to CRP (HR: 1.49; 95%CI: 1.01-2.21) was significantly associated with an increased risk of AF. Our meta-analysis suggested a positive association between elevated CRP levels and incident AF (relative risk: 1.27; 95% CI: 1.14-1.42). However, no significant association between genetically determined CRP and AF risk was observed in the MR analysis. CONCLUSION: Evidence from observational studies suggested that elevated serum CRP levels were positively associated with incident AF, while the causal effects of CRP on AF were not supported by the MR analysis. CLINICAL TRIAL REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR-TNRC-11001489.

Sub-pocket small-hole drainage for pocket hematoma after cardiac device implantation.

AIMS: Pocket hematoma is a common complication associated with cardiac device implantation, but there are limited strategies to deal with this problem. We aimed to evaluate the effectiveness of sub-pocket small-hole drainage (SSD) as a new way to manage severe pocket hematoma. METHODS: A total of 11 patients with severe pocket hematoma were selected for this case series study. The SSD procedure was performed and wound healing was monitored. RESULTS: The SSD procedure was successfully performed on all 11 patients. The time window for SSD was 10-14 days (mean 12.0 ± 1.3 days) after cardiac device implantation. On average, 18.3 ± 2.3 ml of hematoma was drained , with a mean procedural time of 21.3 ± 2.6 min. The patients were followed up for 4-12 months and all pockets healed well, without any complications such as pocket infection, bleeding, device exposure, and electrode fracture. CONCLUSION: Sub-pocket small-hole drainage is an alternative approach for dealing with severe pocket hematoma after cardiac device implantation.

bHLH010/089 Transcription Factors Control Pollen Wall Development via Specific Transcriptional and Metabolic Networks in Arabidopsis thaliana.

The pollen wall is a specialized extracellular cell wall that protects male gametophytes from various environmental stresses and facilitates pollination. Here, we reported that bHLH010 and bHLH089 together are required for the development of the pollen wall by regulating their specific downstream transcriptional and metabolic networks. Both the exine and intine structures of bhlh010 bhlh089 pollen grains were severely defective. Further untargeted metabolomic and transcriptomic analyses revealed that the accumulation of pollen wall morphogenesis-related metabolites, including polysaccharides, glyceryl derivatives, and flavonols, were significantly changed, and the expression of such metabolic enzyme-encoding genes and transporter-encoding genes related to pollen wall morphogenesis was downregulated in bhlh010 bhlh089 mutants. Among these downstream target genes, CSLB03 is a novel target with no biological function being reported yet. We found that bHLH010 interacted with the two E-box sequences at the promoter of CSLB03 and directly activated the expression of CSLB03. The cslb03 mutant alleles showed bhlh010 bhlh089-like pollen developmental defects, with most of the pollen grains exhibiting defective pollen wall structures.

Transcriptomes analysis reveals novel insight into the molecular mechanisms of somatic embryogenesis in Hevea brasiliensis.

BACKGROUND: Somatic embryogenesis (SE) is a promising technology for plant vegetative propagation, which has an important role in tree breeding. Though rubber tree (Hevea brasiliensis Muell. Arg.) SE has been founded, few late SE-related genes have been identified and the molecular regulation mechanisms of late SE are still not well understood. RESULTS: In this study, the transcriptomes of embryogenic callus (EC), primary embryo (PE), cotyledonary embryo (CE), abnormal embryo (AE), mature cotyledonary embryo (MCE) and withered abnormal embryo (WAE) were analyzed. A total of 887,852,416 clean reads were generated, 85.92% of them were mapped to the rubber tree genome. The de novo assembly generated 36,937 unigenes. The differentially expressed genes (DEGs) were identified in the pairwise comparisons of CE vs. AE and MCE vs. WAE, respectively. The specific common DEGs were mainly involved in the phytohormones signaling pathway, biosynthesis of phenylpropanoid and starch and sucrose metabolism. Among them, hormone signal transduction related genes were significantly enriched, especially the auxin signaling factors (AUX-like1, GH3.1, SAUR32-like, IAA9-like, IAA14-like, IAA27-like, IAA28-like and ARF5-like). The transcription factors including WRKY40, WRKY70, MYBS3-like, MYB1R1-like, AIL6 and bHLH93-like were characterized as molecular markers for rubber tree late SE. CML13, CML36, CAM-7, SERK1 and LEAD-29-like were also related to rubber tree late SE. In addition, histone modification had crucial roles during rubber tree late SE. CONCLUSIONS: This study provides important information to elucidate the molecular regulation during rubber tree late SE.

Anatomical insights into posterior wall isolation in patients with atrial fibrillation: A hypothesis to protect the esophagus.

INTRODUCTION: Left atrial posterior wall (LAPW) isolation may be performed as an additional atrial fibrillation (AF) ablation strategy based on pulmonary vein isolation. A modified posterior-inferior line (MPL) was proposed for reducing esophageal injury. The aim of this study was to evaluate the anatomical characteristics of the MPL, compared with the conventional posterior line (CPL). METHODS AND RESULTS: Multidetector computed tomography was performed in 102 consecutive AF patients (male/female = 60/42) preoperative, and the parameters were evaluated as follows: the distance from MPL and CPL to the esophagus, fat pad presence and thickness in the course of MPL and CPL, and the esophageal route below CPL. The average distance from the MPL to the esophagus was longer than from CPL to the esophagus (3.7 ± 1.5 vs. 1.7 ± 0.4 mm, p < .001). Proportion of fat pad was higher in the course of MPL than CPL. The myocardium tissue and fat pad under MPL was thicker than under CPL (2.9 ± 1.1 vs. 1.6 ± 0.3 mm, p < .001; 1.4 ± 0.6 vs. 0.9 ± 0.2 mm, p < .001), respectively. In patients whose esophagus was unconfined in a triangular space at the left inferior pulmonary vein level, the average distance from MPL to esophagus was longer than the confined patients (4.0 ± 1.7 vs. 3.2 ± 1.0 mm, p = .001). CONCLUSION: The MPL was far away from the esophagus with thicker myocardium tissue and more fat pad than the CPL; thus, MPL could serve as a favorable alternative in linear ablation for LAPW isolation.

Tobacco rattle virus-induced gene silencing in Hevea brasiliensis.

Virus-induced gene silencing (VIGS) is a powerful gene-silencing tool that has been intensively applied in plants. To data, the application of VIGS in rubber tree has not yet been reported. In this study, we described the efficient gene silencing in rubber tree by VIGS. The gene encoding Hevea brasiliensis phytoene desaturase (HbPDS) was identified in rubber tree genome. Small interfering RNAs from HbPDS and the silencing gene fragment were predicted and a length of 399 bp was selected to be tested. We showed that the tobacco rattle virus (TRV)-VIGS could induce effective HbPDS silencing in rubber tree. This study was the first to report VIGS in rubber tree. The present TRV-VIGS method could be used to perform reverse genetic approaches to identify unknown gene functions and might be further applied to produce gene silenced rubber tree plants, to advance functional gene of rubber tree.