Development and Validation of a Nomogram of Persistent Pulmonary Hypertension in Adult Pretricuspid Shunts After Correction.

BACKGROUND: Pretricuspid shunts have been associated with poorer survival rates in patients with Eisenmenger syndrome compared with postricuspid shunts and complex lesions. However, the risk stratification for persistent pulmonary hypertension (PH) in this population remains uncertain. METHODS AND RESULTS: We retrospectively enrolled 103 patients with pretricuspid shunts with high total pulmonary resistance >4.5 Wood units (estimated pulmonary vascular resistance ≥3 Wood units). During a mean±SD follow-up of 20.95±24.84 months, 32 patients developed postoperative persistent PH after shunt correction. We identified 3 significant predictors of postoperative persistent PH, including mean pulmonary artery pressure after inhaled oxygen ≥40.5 mm Hg (odds ratio [OR], 7.78 [95% CI, 2.02-30.03]; P<0.01), total pulmonary resistance after inhaled oxygen ≥6.5 Wood units (estimated pulmonary vascular resistance ≥5 Wood units; OR, 12.23 [95% CI, 2.12-70.46]; P<0.01), and artery oxygen saturation at rest <95% (OR, 3.34 [95% CI, 1.07-10.44]; P=0.04). We established the prediction model with the C-statistics of 0.85 (95% CI, 0.77-0.93; P<0.01), and the C-statistic was 0.83 (95% CI, 0.80-0.86) after bootstrapping 10 000 times with a good performance of the nomogram calibration curve for predicting persistent PH. CONCLUSIONS: Our study presents a multivariable risk stratification model for persistent PH after shunt correction in adults with pretricuspid shunts. This model, based on 3 hemodynamic predictors after inhaled oxygen, may assist in identifying individuals at higher risk of persistent PH after shunt correction.

Deciphering protein-mediated underwater adhesion in an invasive biofouling ascidian: Discovery, validation, and functional mechanism of an interfacial protein.

Discovering macromolecules and understanding the associated mechanisms involved in underwater adhesion are essential for both studying the fundamental ecology of benthos in aquatic ecosystems and developing biomimetic adhesive materials in industries. Here, we employed quantitative proteomics to assess protein expression variations during the development of the distinct adhesive structure - stolon in the model fouling ascidian, Ciona robusta. We found 16 adhesive protein candidates with increased expression in the stolon, with ascidian adhesive protein 1 (AAP1) being particularly rich in adhesion-related signal peptides, amino acids, and functional domains. Western blot and immunolocalization analyses confirmed the prominent AAP1 signals in the mantle, tunic, stolon, and adhesive footprints, indicating the interfacial role of this protein. Surface coating and atomic force microscopy experiments verified AAP1's adhesion to diverse materials, likely through the specific electrostatic and hydrophobic amino acid interactions with various substrates. In addition, molecular docking calculations indicated the AAP1's potential for cross-linking via hydrogen bonds and salt bridges among Von Willebrand factor type A domains, enhancing its adhesion capability. Altogether, the newly discovered interfacial protein responsible for permanent underwater adhesion, along with the elucidated adhesion mechanisms, are expected to contribute to the development of biomimetic adhesive materials and anti-fouling strategies. STATEMENT OF SIGNIFICANCE: Discovering macromolecules and studying their associated mechanisms involved in underwater adhesion are essential for understanding the fundamental ecology of benthos in aquatic ecosystems and developing innovative bionic adhesive materials in various industries. Using multidisciplinary analytical methods, we identified an interfacial protein - Ascidian Adhesive Protein 1 (AAP1) from the model marine fouling ascidian, Ciona robusta. The interfacial functions of AAP1 are achieved by electrostatic and hydrophobic interactions, and the Von Willebrand factor type A domain-based cross-linking likely enhances AAP1's interfacial adhesion. The identification and validation of the interfacial functions of AAP1, combined with the elucidation of adhesion mechanisms, present a promising target for the development of biomimetic adhesive materials and the formulation of effective anti-fouling strategies.

Influence of calcium concentration on larval adhesion in a highly invasive fouling ascidian: From morphological changes to molecular mechanisms.

Calcium ion (Ca2+) is involved in the protein-mediated larval adhesion of fouling ascidians, yet the effects of environmental Ca2+ on larval adhesion remain largely unexplored. Here, the larvae of fouling ascidian C. robusta were exposed to different concentrations of Ca2+. Exposures to low-concentration (0 mM and 5 mM) and high-concentration (20 mM and 40 mM) Ca2+ significantly decreased the adhesion rate of larvae, which was primarily attributed to the decreases in adhesive structure length and curvature. Changes in the expressions of genes encoding adhesion-, microvilli-, muscle contraction-, and collagen-related proteins provided a molecular-level explanation for adhesion rate reduction. Additionally, larvae likely prioritized their energy towards immunomodulation in response to Ca2+ stresses, ultimately leading to adhesion reduction. These findings advance our understanding of the influencing mechanisms of environmental Ca2+ on larval adhesion, which are expected to provide references for the development of precise antifouling strategies against ascidians and other fouling species.

eDNA-Based Early Detection Illustrates Rapid Spread of the Non-Native Golden Mussel Introduced into Beijing via Water Diversion.

The world's largest water diversion, the South-to-North Water Transfer Project (SNWTP) in China, has created an "invasion highway" to introduce invasive golden mussels (Limnoperna fortunei) from the Yangtze River basin to Beijing. To examine the spread and colonization patterns of this newly introduced invasive species, we conducted comprehensive environmental DNA (eDNA)-based early detection and conventional field surveys across all water bodies in five river basins in Beijing from 2020 to 2023. Our results indicated a rapid spread over the past four years. Among the 130 tested sites, the number of sites with positive signals from eDNA analysis exhibited an annual increase: Commencing with four infested sites identified through field surveys in 2019, eDNA analysis detected an additional 13, 11, and 10 positive sites in 2020, 2021, and 2022, respectively, and a substantial rise comprising an additional 28 sites in 2023. Conventional field surveys detected mussels 1-3 years later than eDNA-based analysis at 16 sites. Across all 16 sites, we detected a low population density ranging from 1 to 30 individuals/m2. These findings collectively indicate that the invasions by golden mussels in Beijing are still in their early stages. To date, golden mussels have successfully colonized four out of the five investigated river basins, including the Jiyun River (22.2% positive sites), North Canal River (59.6% positive sites), Chaobai River (40% positive sites), and Yongding River (63.6% positive sites), with the North Canal River and Yongding River being the most heavily infested. Currently, only the Daqing River basin remains uninfested. Given the significant number of infested sites and the ongoing transport of large new propagules via SNWTP, further rapid spread and colonization are anticipated across aquatic ecosystems in Beijing and beyond. Consequently, we call for the proper implementation of effective management strategies, encompassing early detection, risk assessment, and the use of appropriate control measures to mitigate the potential ecological and economic damages in invaded ecosystems.

eDNA-based detection reveals invasion risks of a biofouling bivalve in the world's largest water diversion project.

Environmental DNA (eDNA) has increasingly been used to detect rare species (e.g., newly introduced nonindigenous species) in both terrestrial and aquatic ecosystems, often with distinct advantages over traditional methods. However, whether water eDNA signals can be used to inform invasion risks remains debatable owing to inherent uncertainties associated with the methods used and the varying conditions among study systems. Here, we sampled eDNA from canals of the central route of the South-to-North Water Diversion Project (hereafter SNWDP) in China to investigate eDNA distribution and efficacy to inform invasion risks in a unique lotic system. We first conducted a total of 16 monthly surveys in this system (two sites in the source reservoir and four sites in the main canal) to test if eDNA could be applied to detect an invasive, biofouling bivalve, the golden mussel Limnoperna fortunei. Second, we initiated a one-time survey in a sub-canal of the SNWDP using refined sampling (12 sites in ~22 km canal) and considered a few environmental predictors. We found that detection of target eDNA in the main canal was achieved up to 1100 km from the putative source population but was restricted to the warmer months (May-November). Detection probability exhibited a significant positive relationship with average daily minimum air temperature and with water temperature, consistent with the expected spawning season. eDNA concentration in the main canal generally fluctuated across months and sites and was generally higher in warmer months. Golden mussel eDNA concentration in the sub-canal decreased significantly with distance from the source and with increasing water temperature and became almost undetectable at ~22 km distance. Given the enormity of the SNWDP, golden mussels may eventually expand their distribution in the main canal, with established "bridgehead" populations facilitating further spread. Our findings suggest an elevated invasion risk of golden mussels in the SNWDP in warm months, highlighting the critical period for spread and, possibly, management.

Effects of Biological Nitrogen Metabolism on Glufosinate-Susceptible and -Resistant Goosegrass (Eleusine indica L.).

Glufosinate is a broad-spectrum herbicide used to control most weeds in agriculture worldwide. Goosegrass (Eleusine indica L.) is one of the top ten malignant weeds across the world, showing high tolerance to glufosinate via different mechanisms that are not yet fully understood. This study revealed that nitrogen metabolism could be a target-resistant site, providing clues to finally clarify the mechanism of glufosinate resistance in resistant goosegrass populations. Compared to susceptible goosegrass (NX), the resistant goosegrass (AUS and CS) regarding the stress of glufosinate showed stronger resistance with lower ammonia contents, higher target enzyme GS (glutamine synthetase) activity, and lower GOGAT (glutamine 2-oxoglutarate aminotransferase) activity. The GDH (glutamate dehydrogenase) activity of another pathway increased, but its gene expression was downregulated in resistant goosegrass (AUS). Analyzing the transcriptome and proteome data of goosegrass under glufosinate stress at 36 h showed that the KEGG pathway of the nitrogen metabolism was enriched in glufosinate-susceptible goosegrass (NX), but not in glufosinate-resistant goosegrass (CS and AUS). Several putative target genes involved in glufosinate stress countermeasures were identified. This study provides specific insights into the nitrogen metabolism of resistant goosegrass, and gives a basis for future functional verification of glufosinate-tolerance genes in plants.

Nine new species of black lichenicolous fungi from the genus Cladophialophora (Chaetothyriales) from two different climatic zones of China.

Lichenicolous fungi are parasites of lichens. Many of these fungi are referred to as "black fungi". A diversity of these black fungi include species that are pathogenic to humans and plants. A majority of black fungi reside in the phylum Ascomycota within the sub-classes Chaetothyriomycetidae and Dothideomycetidae. To explore the diversity of lichenicolous "black fungi" associated with lichens in China, we conducted several field surveys in the Inner Mongolia Autonomous Region and Yunnan Province between 2019 and 2020. We recovered 1,587 fungal isolates from the lichens collected during these surveys. During the preliminary identification of these isolates using the complete internal transcribed spacer (ITS), partial large subunit of nuclear ribosomal RNA gene (LSU), and small subunit of nuclear ribosomal RNA gene (SSU), we identified 15 fungal isolates from the genus Cladophialophora. However, these isolates had low sequence similarities with all known species from the genus. Therefore, we amplified additional gene regions, such as, translation elongation factor (TEF) and partial ß-tubulin gene (TUB), and constructed a multi-gene phylogeny using maximum likelihood, maximum parsimony, and Bayesian inference. In our datasets, we included type sequences where available for all Cladophialophora species. Phylogenetic analyses revealed that none of the 15 isolates belonged to any of the previously described species in the genus. Therefore, using both morphological and molecular data, we classified these 15 isolates as nine new species within the genus Cladophialophora: C. flavoparmeliae, C. guttulate, C. heterodermiae, C. holosericea, C. lichenis, C. moniliformis, C. mongoliae, C. olivacea, and C. yunnanensis. The outcome from this study shows that lichens are an important refugia for black lichenicolous fungi, such as those from Chaetothyriales.

Fungal Diversity Associated with Thirty-Eight Lichen Species Revealed a New Genus of Endolichenic Fungi, Intumescentia gen. nov. (Teratosphaeriaceae).

Fungi from the Teratosphaeriaceae (Mycosphaerellales; Dothideomycetes; Ascomycota) have a wide range of lifestyles. Among these are a few species that are endolichenic fungi. However, the known diversity of endolichenic fungi from Teratosphaeriaceae is far less understood compared to other lineages of Ascomycota. We conducted five surveys from 2020 to 2021 in Yunnan Province of China, to explore the biodiversity of endolichenic fungi. During these surveys, we collected multiple samples of 38 lichen species. We recovered a total of 205 fungal isolates representing 127 species from the medullary tissues of these lichens. Most of these isolates were from Ascomycota (118 species), and the remaining were from Basidiomycota (8 species) and Mucoromycota (1 species). These endolichenic fungi represented a wide variety of guilds, including saprophytes, plant pathogens, human pathogens, as well as entomopathogenic, endolichenic, and symbiotic fungi. Morphological and molecular data indicated that 16 of the 206 fungal isolates belonged to the family Teratosphaeriaceae. Among these were six isolates that had a low sequence similarity with any of the previously described species of Teratosphaeriaceae. For these six isolates, we amplified additional gene regions and conducted phylogenetic analyses. In both single gene and multi-gene phylogenetic analyses using ITS, LSU, SSU, RPB2, TEF1, ACT, and CAL data, these six isolates emerged as a monophyletic lineage within the family Teratosphaeriaceae and sister to a clade that included fungi from the genera Acidiella and Xenopenidiella. The analyses also indicated that these six isolates represented four species. Therefore, we established a new genus, Intumescentia gen. nov., to describe these species as Intumescentia ceratinae, I. tinctorum, I. pseudolivetorum, and I. vitii. These four species are the first endolichenic fungi representing Teratosphaeriaceae from China.

Interventional Occlusion of Large Patent Ductus Arteriosus in Adults with Severe Pulmonary Hypertension.

(1) Background: the indications for transcatheter closure of large patent ductus arteriosus (PDA) with severe pulmonary hypertension (PH) are still unclear, and scholars have not fully elucidated the factors that affect PH prognosis. (2) Methods: we retrospectively enrolled 134 consecutive patients with a PDA diameter ≥10 mm or a ratio of PDA and aortic >0.5. We collected clinical data to explore the factors affecting follow-up PH. (3) Results: 134 patients (mean age 35.04 ± 10.23 years; 98 women) successfully underwent a transcatheter closure, and all patients had a mean pulmonary artery pressure (mPAP) >50 mmHg. Five procedures were deemed to have failed because their mPAP did not decrease, and the patients experienced uncomfortable symptoms after the trial occlusion. The average occluder (pulmonary end) size was almost twice the PDA diameter (22.33 ± 4.81 mm vs. 11.69 ± 2.18 mm). Left ventricular end-diastolic dimension (LVEDD), mPAP, and left ventricular ejection fraction (LVEF) significantly reduced after the occlusion, and LVEF recovered during the follow-up period. In total, 42 of the 78 patients with total pulmonary resistance >4 Wood Units experienced clinical outcomes, and all of them had PH in the follow-up, while 10 of them had heart failure, and 4 were hospitalized again because of PH. The results of a logistic regression analysis revealed that the postoperative mPAP had an independent risk factor (odds ratio = 1.069, 95% confidence interval: 1.003 to 1.140, p = 0.040) with a receiver operating characteristic curve cut-off value of 35.5 mmHg (p < 0.001). (4) Conclusions: performing a transcatheter closure of large patent ductus arteriosus is feasible, and postoperative mPAP was a risk factor that affected the follow-up PH. Patients with a postoperative mPAP >35.5 mmHg should be considered for targeted medical therapy or should undergo right heart catheterization again after the occlusion.

Mechanism of METTL3-Mediated m6A Modification in Cardiomyocyte Pyroptosis and Myocardial Ischemia-Reperfusion Injury.

OBJECTIVE: Myocardial ischemia/reperfusion (MI/R) injury is a complicated pathophysiological process associated with cardiomyocyte pyroptosis. Methyltransferase-like protein 3 (METTL3) catalyzes the formation of N6-methyl-adenosine (m6A) and participates in various biological processes. This study probed into the mechanism of METTL3 in cardiomyocyte pyroptosis in MI/R injury. METHODS: A rat model of MI/R was established. Rat cardiomyocytes were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) treatment for the establishment of a cell model in vitro. METTL3 expression in myocardial tissues of MI/R rats and OGD/R-treated cardiomyocytes was determined using RT-qPCR and Western blot. The pathological changes of rat myocardial tissues were observed using hematoxylin and eosin staining. The positive expression of NLRP3 in myocardial tissues or cardiomyocytes was observed through immunohistochemistry or immunofluorescence. The activity of caspase-1 was measured using the colorimetric method. The expressions of GSDMD and cleaved caspase-1, as well as the levels of IL-1ß and IL-18 in rat myocardial tissues or cardiomyocytes were determined. m6A modification level was quantified. The binding relationship between pri-miR-143-3p and DGCR8 and the enrichment of m6A on pri-miR-143-3p were detected. The binding relationship between miR-143-3p and protein kinase C epsilon (PRKCE) was verified. RESULTS: METTL3 expression was elevated in MI/R rats and OGD/R cardiomyocytes. METTL3 silencing alleviated myocardial injury, reduced the number of NLRP3-positive cardiomyocytes, suppressed caspase-1 activity, decreased the protein levels of GSDMD-N and cleaved caspase-1, and decreased IL-1ß and IL-18 levels. METTL3 increased the total m6A level in MI/R rats and injured cardiomyocytes, promoted DGCR8 binding to pri-miR-143-3p, and enhanced miR-143-3p expression. miR-143-3p suppressed PRKCE transcription, and miR-143-3p overexpression reversed the inhibitory effect of METTL3 silencing on cardiomyocyte pyroptosis. CONCLUSION: METTL3 promoted DGCR8 binding to pri-miR-143-3p through m6A modification, thus enhancing miR-143-3p expression to inhibit PRKCE transcription and further aggravating cardiomyocyte pyroptosis and MI/R injury.

(Epi)genomic adaptation driven by fine geographical scale environmental heterogeneity after recent biological invasions.

Elucidating processes and mechanisms involved in rapid local adaptation to varied environments is a poorly understood but crucial component in management of invasive species. Recent studies have proposed that genetic and epigenetic variation could both contribute to ecological adaptation, yet it remains unclear on the interplay between these two components underpinning rapid adaptation in wild animal populations. To assess their respective contributions to local adaptation, we explored epigenomic and genomic responses to environmental heterogeneity in eight recently colonized ascidian (Ciona intestinalis) populations at a relatively fine geographical scale. Based on MethylRADseq data, we detected strong patterns of local environment-driven DNA methylation divergence among populations, significant epigenetic isolation by environment (IBE), and a large number of local environment-associated epigenetic loci. Meanwhile, multiple genetic analyses based on single nucleotide polymorphisms (SNPs) showed genomic footprints of divergent selection. In addition, for five genetically similar populations, we detected significant methylation divergence and local environment-driven methylation patterns, indicating the strong effects of local environments on epigenetic variation. From a functional perspective, a majority of functional genes, Gene Ontology (GO) terms, and biological pathways were largely specific to one of these two types of variation, suggesting partial independence between epigenetic and genetic adaptation. The methylation quantitative trait loci (mQTL) analysis showed that the genetic variation explained only 18.67% of methylation variation, further confirming the autonomous relationship between these two types of variation. Altogether, we highlight the complementary interplay of genetic and epigenetic variation involved in local adaptation, which may jointly promote populations' rapid adaptive capacity and successful invasions in different environments. The findings here provide valuable insights into interactions between invaders and local environments to allow invasive species to rapidly spread, thus contributing to better prediction of invasion success and development of management strategies.

Assessment of alterations in histone modification function and guidance for death risk prediction in cervical cancer patients.

Background: Cervical cancer is the second most lethal malignancy among women, and histone modification plays a fundamental role in most biological processes, but the prognostic value of histone modification in cervical cancer has not been evaluated. Methods: A total of 594 cervical cancer patients from TCGA-CESC, GSE44001, and GSE52903 cohorts were enrolled in the current study, along with the corresponding clinicopathological features. Patients with a follow-up time less than one month were removed. A total of 122 histone modification-associated signaling pathways were obtained from the MSigDB. The activation scores of these pathways were evaluated using the "GSVA" package, differentially expressed genes were identified by the "limma" package, and pathway enrichment was conducted using the "clusterProfiler 4.0" package. The subsequent least absolute shrinkage and selection operator (LASSO) regression analysis was performed using the "glmnet" package, and a prognostic nomogram was established using the "regplot" package. For the prediction of potential therapeutic drugs, we used the data from GDSC2016 and visualized them via "MOVICS". Results: Nine of 23 histone modification-associated prognostic genes were identified to construct the prognostic signature by LASSO analysis, named the histone modification-associated gene (HMAG) signature. Cervical patients with HMAG-H in TCGA-CESC cohort showed a 2.68-fold change of death risk, with the 95% CI from 1.533 to 4.671 (p < 0.001), as well as the increased death risk of HMAG-H in the GSE44001 cohort (HR: 2.83, 95% CI: 1.370-5.849, p = 0.005) and GSE44001 cohort (HR: 4.59, 95% CI: 1.658-12.697, p = 0.003). We observed the preferable AUC values of the HMAG signature in TCGA-CESC cohort (1-year: 0.719, 3-year: 0.741, and 5-year: 0.731) and GSE44001 cohort (1-year: 0.850, 3-year: 0.781, and 5-year: 0.755). The C-index of the nomogram showed a prognostic value as high as 0.890, while the C-index for age was only 0.562, and that for grade was only 0.542. Patients with high HMAG scores were more suitable for the treatment of CHIR-99021, embelin, FTI-277, JNK-9L, JQ12, midostaurin, PF-562271, pyrimethamine, and thapsigargin, and patients with low HMAG scores were more suitable for the treatment of BMS-536924, CP466722, crizotinib, PHA-665752, rapamycin, and TAE684. Conclusion: We comprehensively evaluated the histone modification status in cervical cancer patients and revealed histone modification-associated prognostic genes to construct the HMAG signature, aiming to provide a new insight into prognosis prediction and precise clinical treatment.

Transcatheter closure of inferior sinus venosus defect using a patent ductus arteriosus occluder following simulation with a 3D-printed model.

Background: Transcatheter closure of inferior sinus venosus defect (ISVD) is still contraindication. To explore whether transcatheter closure with patent ductus arteriosus (PDA) occluders is possible for ISVD. Methods: From June 2014 to March 2021, 12 patients were recruited diagnosed as <25 mm ISVD. The three-dimensional printing (3DP) heart model was produced based on multi-slice computed tomography (MSCT) scans. Preoperative closure simulation was planned on the personalized 3D model for each patient. Follow-up including electrocardiography (ECG), transthoracic echocardiography (TTE), and X-ray was traced. Results: 3DP models of 12 patients were successfully printed. Twelve patients had been diagnosed with <25 mm ISVD and 4 of them had another secundum atrial septal defect (ASD). All patients were produced interventional therapy successfully. PDA occluder was implanted to closed ISVD, and ASD was closed using ASD occluder simultaneously. The average diameter of ISVD measured by TTE was (12.67±3.80), and the average diameter of sagittal axes and longitudinal axes measured by the 3D-printed model was (17.08±3.20) and (18.42±4.62) mm, respectively. The average size of PDA (diameter of pulmonary artery side) was (28.17±3.35) mm. Compared with the preoperative, the X-ray cardiothoracic ratio (0.51±0.04 vs. 0.47±0.06, P=0.007) and the right ventricle anterior-posterior diameter (31.17±5.65 vs. 24.58±3.75 mm, P<0.001) of postoperative was significantly decreased. During the average (47.75±27.52) months follow-up, it has achieved satisfying results, and there were no severe adverse events such as device transposition, death, and pericardial tamponade occurred. Conclusions: Assisting by 3D heart model, transcatheter closure of ISVD with PDA occluder had an excellent outcome. This method provides a new considerable treatment strategy for ISVD.

First in-human modified atrial septostomy combining radiofrequency ablation and balloon dilation.

OBJECTIVE: Preclinical research suggests that the combined use of radiofrequency ablation and balloon dilation (CURB) could create stable interatrial communications without device implantation. This study examined the first in-human use of CURB for modified atrial septostomy in patients with severe pulmonary arterial hypertension (PAH). METHODS: Between July 2018 and October 2021, CURB was performed in 19 patients with severe PAH (age: 31.5±9.1 years; mean pulmonary artery pressure: 73 mm Hg (IQR: 66-92); pulmonary vascular resistance: 18.7 Wood units (IQR: 17.8-23.3)). Under guidance of intracardiac echocardiography and three-dimensional location system, (1) fossae ovalis was reconstructed and ablated point-by-point with radiofrequency; (2) then graded balloon dilation was performed after transseptal puncture and the optimal size was determined according to the level of arterial oxygen saturation (SatO2); (3) radiofrequency ablation was repeated around the rims of the created fenestration. The interatrial fenestrations were followed-up serially. RESULTS: After CURB, the immediate fenestration size was 4.4 mm (IQR: 4.1-5.1) with intracardiac echocardiography, systolic aortic pressure increased by 10.2±6.9 mm Hg, cardiac index increased by 0.7±0.3 L/min/m2 and room-air resting SatO2 decreased by 6.2±1.9% (p<0.001). One patient experienced increased pericardiac effusion postoperatively; the others had no complications. On follow-up (median: 15.5 months), all interatrial communications were patent with stable size (intraclass correlation coefficient=0.96, 95%CI:0.89 to 0.99). The WHO functional class increased by 1 (IQR: 1-2) (p<0.001) with improvement of exercise capacity (+159.5 m, P<0.001). CONCLUSION: The interatrial communications created with CURB in patients with severe PAH were stable and the mid-term outcomes were satisfactory. TRIAL REGISTRATION NUMBER: NCT03554330.

Complementary genomic and epigenomic adaptation to environmental heterogeneity.

While adaptation is commonly thought to result from selection on DNA sequence-based variation, recent studies have highlighted an analogous epigenetic component as well. However, the relative roles of these mechanisms in facilitating population persistence under environmental heterogeneity remain unclear. To address the underlying genetic and epigenetic mechanisms and their relationship during environmental adaptation, we screened the genomes and epigenomes of nine global populations of a predominately sessile marine invasive tunicate, Botryllus schlosseri. We detected clear population differentiation at the genetic and epigenetic levels. Patterns of genetic and epigenetic structure were significantly influenced by local environmental variables. Among these variables, minimum annual sea surface temperature was identified as the top explanatory variable for both genetic and epigenetic variation. However, patterns of population structure driven by genetic and epigenetic variation were somewhat distinct, suggesting possible autonomy of epigenetic variation. We found both shared and specific genes and biological pathways among genetic and epigenetic loci associated with environmental factors, consistent with complementary and independent contributions of genetic and epigenetic variation to environmental adaptation in this system. Collectively, these mechanisms may facilitate population persistence under environmental change and sustain successful invasions across novel environments.

Microplastics boost the accumulation of tetrabromobisphenol A in a commercial clam and elevate corresponding food safety risks.

Marine bivalve molluscs are one of the primary seafood for consumers. Inhabiting terrigenous pollutant-convergent coastal areas and feeding through seawater filtration, edible bivalves are subjected to waterborne emerging pollutants such as microplastics (MPs) and tetrabromobisphenol A (TBBPA). Nevertheless, the potential risks of consuming MP-TBBPA contaminated seafood are still largely unknown. With that, accumulation of TBBPA with and without the presence of MPs in a commercial bivalve species, blood clam (Tegillarca granosa), was determined in the present study. Meanwhile, corresponding target hazard quotients (THQs) as well as margins of exposure (MoEs) were estimated to evaluate the potential health risks for clam consumers. Furthermore, the impacts of pollutants accumulation on the detoxification process and energy supply were analysed. The data obtained demonstrated that MPs aggravate the accumulation of TBBPA in clams, leading to elevated potential food safety risks (indicated by higher THQ values and lower MoE values) for consumers. In addition, the in vivo contents of CYP1A1 and UDP-glucuronosyltransferase, the enzymatic activity of glutathione-S-transferase, and the expression levels of five detoxification-related genes were all dramatically suppressed by MP-TBBPA. Furthermore, clams exposed to MP-TBBPA had significantly lower adenosine triphosphate contents and lower pyruvate kinase and phosphofructokinase activities. These results indicated that the aggravation of TBBPA accumulation may be due to the hence disruption of detoxification process and limited energy available for detoxification.

Protein-mediated bioadhesion in marine organisms: A review.

Protein-mediated bioadhesion is one of the crucial physiological processes in marine organisms, by which they can firmly adhere to underwater substrates. Most marine adhesive organisms are biofoulers, causing negative effects on marine ecosystems and huge economic losses to aquaculture and maritime industries. Furthermore, adhesive proteins in these organisms are promising bionic candidates for high-performance artificial materials with great application value. In-depth understanding of the bioadhesion in marine ecosystems is of dual significance for resolving biofouling issue and developing marine bionic products. Here, we review the research progress of protein-mediated bioadhesion in marine organisms. The adhesion processes such as protein biosynthesis and secretion are similar among organisms, but the detailed features such as compositions, structures, and molecular functions of adhesive proteins are distinct. Hydroxylation, glycosylation, and phosphorylation are important post-translational modifications during the processes of adhesion. The contents of some amino acids such as glycine, tyrosine and cysteine involved in underwater adhesion are significantly higher, which is a sequence feature of barnacle cement and mussel foot proteins. The amyloid structures and conserved domains/motifs such as EGF and vWFA distributed in adhesive proteins are involved in the underwater adhesion. In addition, the oxidative cross-linking also plays an important role in marine bioadhesion. Overall, the unique and common features identified for the protein-mediated bioadhesion in diverse marine organisms here provide background information and essential reference for characterizing marine adhesive proteins and associated functional domains, formulating antifouling strategies, and developing novel biomimetic adhesives.

Local environment-driven adaptive evolution in a marine invasive ascidian (Molgula manhattensis).

Elucidating molecular mechanisms of environment-driven adaptive evolution in marine invaders is crucial for understanding invasion success and further predicting their future invasions. Although increasing evidence suggests that adaptive evolution could contribute to organisms' adaptation to varied environments, there remain knowledge gaps regarding how environments influence genomic variation in invaded habitats and genetic bases underlying local adaptation for most marine invaders. Here, we performed restriction-site-associated DNA sequencing (RADseq) to assess population genetic diversity and further investigate genomic signatures of local adaptation in the marine invasive ascidian, Molgula manhattensis. We revealed that most invasive populations exhibited significant genetic differentiation, low recent gene flow, and no signal of significant population bottleneck. Based on three genome scan approaches, we identified 109 candidate loci potentially under environmental selection. Redundancy analysis and variance partitioning analysis suggest that local environmental factors, particularly the salinity-related variables, represent crucial evolutionary forces in driving adaptive divergence. Using the newly developed transcriptome as a reference, 14 functional genes were finally obtained with potential roles in salinity adaptation, including SLC5A1 and SLC9C1 genes from the solute carrier gene (SLC) superfamily. Our findings confirm that differed local environments could rapidly drive adaptive divergence among invasive populations and leave detectable genomic signatures in marine invaders.

Effectiveness and Mechanisms of Recoverable Magnetic Nanoparticles on Mitigating Golden Mussel Biofouling.

Mussel biofouling has become a problem in aquatic ecosystems, causing significant ecological impact and huge economic loss globally. Although several strategies have been proposed and tested, efficient and environment-friendly antifouling methods are still scarce. Here, we investigated the effects of recoverable magnetic ferroferric oxide nanoparticles (Fe3O4-NPs) with different sizes (10 and 100 nm), coatings (polyethylene glycol and polylysine), and concentrations (0.01 and 0.1 mg/L) on byssus adhesion-mediated biofouling by the notorious golden mussel Limnoperna fortunei. The results showed that magnetic Fe3O4-NPs, especially negatively charged polyethylene glycol-coated Fe3O4-NPs, size- and concentration-dependently reduced the byssus production, performance (breaking force and failure location), and adhesion rate. Further investigations on mechanisms showed that the down-regulation of foot protein 2 (Lffp-2) and energy-related metabolic pathways inhibited byssus production. The declined gene expression level and metal-binding ability of Lffp-2 significantly affected foot protein interactions, further reducing the plaque size and byssus performance. In addition, the change in the water redox state likely reduced byssus performance by preventing the interface interactions between the substrate and foot proteins. Our results confirm the effectiveness and underlying mechanisms of magnetic Fe3O4-NPs on mitigating L. fortunei biofouling, thus providing a reference for developing efficient and environment-friendly antifouling strategies against fouling mussels.