Blocking lactate regulation of the Grhl2/SLC31A1 axis inhibits trophoblast cuproptosis and preeclampsia development.

PURPOSE: Abnormal cell death due to superficial trophoblast dysfunction caused by placental hypoxia plays a vital role in the development of preeclampsia (PE). Lactic acid stimulates gene transcription in chromatin through lactate modification of histone lysine. Nevertheless, the content and function of lactate in PE development remains largely unclear. METHODS: The contents of lactic acid and copper in 30 PE and 30 normal placentas were determined by kit colorimetry. Real-time quantitative fluorescent PCR (qRT-PCR) and Western blot were used to detect the expression of SLC31A1 in cells and tissues. Cell proliferation, apoptosis, and invasion were detected by cell counting kit 8 (CCK-8), MTS assay, colony formation assay, and Transwell assay. The transcriptional regulation between Grhl2 and SLC31A was verified by the luciferase reporter gene method and ChIP. The H3K18la modification level was detected by ChIP-PCR. RESULTS: Herein, we detected increased lactic acid levels in the PE placental tissue, which inhibit the proliferation and invasion of trophoblasts. Interestingly, lactic acid increases intracellular copper content by enhancing the expression of SLC31A1, a key protein of copper ion transporters. Lentivirus knockdown of SLC31A1 blocked the lactate-induced proliferation and invasion of trophoblasts by inhibiting cell cuproptosis. Mechanically, we identified that Grhl2 mediated SLC31A1 expression through transcription and participated in SLC31A1-inhibited proliferation, invasion, and cuproptosis of trophoblasts. Furthermore, the high lactate content increased Grhl2 expression by enhancing lactate modification of histone H3K18 in the Grhl2 promoter region. CONCLUSIONS: Blocking the lactate-regulated Grhl2/SLC31A1 axis and trophoblastic cuproptosis may be a potential approach to prevent and treat PE.

Acupuncture for stroke: A bibliometric analysis of global research from 2000 to 2022.

Objective: This study aimed to explore the global and future research trends in acupuncture interventions for stroke between 2000 and 2022 using bibliometric analysis. Method: A bibliometric analysis of literature from 2000 to 2022 in the Web of Science Core Collection was conducted in this study. The analysis utilized CiteSpace, VOSviewer, and Scimago Graphica software to identify the major contributors to publications, including authors, countries, institutions, journals, references, and keywords. Results: The bibliometric analysis yielded a total of 860 publications. There was a gradual increase in the number of publications over the study period. China published the most articles. Evidence-Based Complementary and Alternative Medicine was the journal with the greatest number of publications. The most frequently used keywords were "acupuncture," "stroke," and "electroacupuncture." Conclusion: These analysis uncovers the research trends in acupuncture for stroke spanning 2000 to 2022 and points to prospective research frontiers. This study provides a deeper and more thorough understanding of the connotations of acupuncture for stroke and guidance and support for future research in this field.

Exploring the cobia (Rachycentron canadum) genome: unveiling putative male heterogametic regions and identification of sex-specific markers.

BACKGROUND: Cobia (Rachycentron canadum) is the only member of the Rachycentridae family and exhibits considerable sexual dimorphism in growth rate. Sex determination in teleosts has been a long-standing basic biological question, and the molecular mechanisms of sex determination/differentiation in cobia are completely unknown. RESULTS: Here, we reported 2 high-quality, chromosome-level annotated male and female cobia genomes with assembly sizes of 586.51 Mb (contig/scaffold N50: 86.0 kb/24.3 Mb) and 583.88 Mb (79.9 kb/22.5 Mb), respectively. Synteny inference among perciform genomes revealed that cobia and the remora Echeneis naucrates were sister groups. Further, whole-genome resequencing of 31 males and 60 females, genome-wide association study, and sequencing depth analysis identified 3 short male-specific regions within a 10.7-kb continuous genomic region on male chromosome 18, which hinted at an undifferentiated sex chromosome system with a putative XX/XY mode of sex determination in cobia. Importantly, the only 2 genes within/between the male-specific regions, epoxide hydrolase 1 (ephx1, renamed cephx1y) and transcription factor 24 (tcf24, renamed ctcf24y), showed testis-specific/biased gene expression, whereas their counterparts cephx1x and ctf24x, located in female chromosome 18, were similarly expressed in both sexes. In addition, male-specific PCR targeting the cephx1y gene revealed that this genomic feature is conserved in cobia populations from Panama, Brazil, Australia, and Japan. CONCLUSION: The first comprehensive genomic survey presented here is a valuable resource for future studies on cobia population structure and dynamics, conservation, and evolutionary history. Furthermore, it establishes evidence of putative male heterogametic regions with 2 genes playing a potential role in the sex determination of the species, and it provides further support for the rapid evolution of sex-determining mechanisms in teleost fish.

Impact of transport conditions and underlying disease on post-stocking survival of juvenile Lates calcarifer.

Diseases caused by pathogens commonly occurring in the aquatic environment or those that are non-host specific are prevalent and threaten the rapid growth of tropical aquaculture. This study investigates causes of mortality in 12 batches of newly stocked juvenile Lates calcarifer from three different hatcheries. Cytology based on Diff-Quik™-stained tissue and blood smears provides rapid diagnosis of possible causes of mortality, while histopathology and haematology provide a better understanding of how prolonged transport and fish with existing chronic disease are more likely to experience elevated mortality post-stocking. Our findings showed that accumulation of ammonia during prolonged transport causes extensive damage to epithelial barriers in gastrointestinal tracts and depressed immunity due to marked hypoglycaemia, predisposing fish to acute Streptococcosis. Lates calcarifer with chronic bacterial enteritis developed severe hypoglycaemia, had low circulating total plasma protein, and suffered high mortality within 24 hours post-stocking. Hypoglycaemia and low circulating blood proteins disrupt osmoregulation and exacerbate dehydration, which is fatal in fish in sea water. Dying L. calcarifer tested PCR positive for scale drop disease virus (SDDV) at 28 days post-stocking showed a 10-fold elevation of white blood cell counts, severe vasculitis, and obstruction of blood supply to major organs. Destruction of important immune organs such as spleen is a hallmark of SDDV infection that explains high incidences of opportunistic Vibrio harveyi infections in 61% of fish with SDDV. Overall, this study reiterates the importance of stocking disease-free fish and reducing transport stress.

Case report: Treatment of Wilson's disease by human amniotic fluid administration.

Background: Wilson's disease (WD) is not an uncommon genetic disease in clinical practice. However, the current WD therapies have limitations. The effectiveness of stem cell therapy in treating WD has yet to be verified, although a few animal studies have shown that stem cell transplantation could partially correct the abnormal metabolic phenotype of WD. In this case report, we present the therapeutic effect of human amniotic fluid containing stem cells in one WD patient. Case presentation: A 22-year-old Chinese woman was diagnosed with WD 1 year ago in 2019. The available drugs were not effective in managing the progressive neuropsychiatric symptoms. We treated the patient with pre-cultured human amniotic fluid containing stem cells. Amniotic fluid was collected from pregnant women who underwent induced labor at a gestational age of 19-26 weeks, and then, the fluid was cultured for 2 h to allow stem cell expansion. Cultured amniotic fluid that contained amniotic fluid derived stem cells (AFSC) in the range of approximately 2.8-5.5 × 104/ml was administrated by IV infusion at a rate of 50-70 drops per minute after filtration with a 300-mu nylon mesh. Before the infusion of amniotic fluid, low-molecular-weight heparin and dexamethasone were successively administrated. The patient received a total of 12 applications of amniotic fluid from different pregnant women, and the treatment interval depended on the availability of amniotic fluid. The neuropsychiatric symptoms gradually improved after the stem cell treatment. Dystonia, which included tremor, chorea, dysphagia, dysarthria, and drooling, almost disappeared after 1.5 years of follow-up. The Unified Wilson's Disease Rating Scale score of the patient decreased from 72 to 10. Brain magnetic resonance imaging (MRI) showed a reduction in the lesion area and alleviation of damage in the central nervous system, along with a partial recovery of the lesion to the normal condition. The serum ceruloplasmin level was elevated from undetectable to 30.8 mg/L, and the 24-h urinary copper excretion decreased from 171 to 37 µg. In addition, amniotic fluid transplantation also alleviates hematopoietic disorders. There were no adverse reactions during or after amniotic fluid administration. Conclusion: Amniotic fluid administration, through which stem cells were infused, significantly improves the clinical outcomes in the WD patient, and the finding may provide a novel approach for managing WD effectively.

Blocking the interaction between circTNRC18 and LIN28A promotes trophoblast epithelial-mesenchymal transformation and alleviates preeclampsia.

Defects in migration and invasion caused by dysregulation of trophoblastic epithelial-mesenchymal transformation (EMT) play a vital role in preeclampsia (PE). We have previously shown that circTNRC18 inhibits the migration and EMT of trophoblasts; however, its role in PE remains unknown. Herein, we demonstrate that circTNRC18 interacts with an RNA-binding protein, lin-28 homolog A (LIN28A), and this interaction is enhanced in PE placental tissue. LIN28A overexpression suppresses circTNRC18-mediated inhibition of trophoblast migration, invasion, and EMT, whereas LIN28A knockdown promotes them. The intracellular distribution of LIN28A is regulated by circTNRC18, where it promotes the expression of insulin-like growth factor II by stabilizing its mRNA. circTNRC18 also promotes complex formation between GATA-binding factor 1 (GATA1) and sine oculis homeobox 1 (SIX1) by inhibiting LIN28A-GATA1 interaction. GATA1-SIX1 promotes transcription of grainyhead-like protein 2 homolog and circTNRC18-mediated regulation of cell migration and invasion. Moreover, blocking circTNRC18-LIN28A interaction with antisense nucleotides alleviates PE in a mouse model of reduced uterine perfusion pressure. Thus, targeting the circTNRC18-LIN28A regulatory axis may be a novel PE treatment method.

Mapping of a major QTL for increased robustness and detection of genome assembly errors in Asian seabass (Lates calcarifer).

BACKGROUND: For Asian seabass (Lates calcarifer, Bloch 1790) cultured at sea cages various aquatic pathogens, complex environmental and stress factors are considered as leading causes of disease, causing tens of millions of dollars of annual economic losses. Over the years, we conducted farm-based challenges by exposing Asian seabass juveniles to complex natural environmental conditions. In one of these challenges, we collected a total of 1,250 fish classified as either 'sensitive' or 'robust' individuals during the 28-day observation period. RESULTS: We constructed a high-resolution linkage map with 3,089 SNPs for Asian seabass using the double digest Restriction-site Associated DNA (ddRAD) technology and a performed a search for Quantitative Trait Loci (QTL) associated with robustness. The search detected a major genome-wide significant QTL for increased robustness in pathogen-infected marine environment on linkage group 11 (ASB_LG11; 88.9 cM to 93.6 cM) with phenotypic variation explained of 81.0%. The QTL was positioned within a > 800 kb genomic region located at the tip of chromosome ASB_LG11 with two Single Nucleotide Polymorphism markers, R1-38468 and R1-61252, located near to the two ends of the QTL. When the R1-61252 marker was validated experimentally in a different mass cross population, it showed a statistically significant association with increased robustness. The majority of thirty-six potential candidate genes located within the QTL have known functions related to innate immunity, stress response or disease. By utilizing this ddRAD-based map, we detected five mis-assemblies corresponding to four chromosomes, namely ASB_LG8, ASB_LG9, ASB_LG15 and ASB_LG20, in the current Asian seabass reference genome assembly. CONCLUSION: According to our knowledge, the QTL associated with increased robustness is the first such finding from a tropical fish species. Depending on further validation in other stocks and populations, it might be potentially useful for selecting robust Asian seabass lines in selection programs.

Comparative gonad transcriptome analysis in cobia (Rachycentron canadum).

Background: Cobia (Rachycentron canadum) is a species of fish with high commercial potential particularly due to fast growth rates. The evidence of sexual size dimorphism favoring females indicate potential benefits in having a monosex culture. However, the involvement of genetic factors responsible for sexual development and gonadal maintenance that produces phenotypic sex in cobia is largely unknown. Methods: In the present study, we performed transcriptome sequencing of cobia to identify sex-biased significantly differentially expressed genes (DEGs) in testes and ovaries. The reliability of the gonad transcriptome data was validated by qPCR analysis of eight selected significantly differential expressed sex-related candidate genes. Results: This comparative gonad transcriptomic analysis revealed that 7,120 and 4,628 DEGs are up-regulated in testes or ovaries, respectively. Further functional annotation analyses identified 76 important candidate genes involved in sex determination cascades or sex differentiation, including 42 known testis-biased DEGs (dmrt1, amh and sox9 etc.), and 34 known ovary-biased DEGs (foxl2, sox3 and cyp19a etc.). Moreover, eleven significantly enriched pathways functionally related to sex determination and sex differentiation were identified, including Wnt signaling pathway, oocyte meiosis, the TGF-beta signaling pathway and MAPK signaling pathway. Conclusion: This work represents the first comparative gonad transcriptome study in cobia. The putative sex-associated DEGs and pathways provide an important molecular basis for further investigation of cobia's sex determination, gonadal development as well as potential control breeding of monosex female populations for a possible aquaculture setting.

The Muscle Activation Differences in Post-Stroke Upper Limb Flexion Synergy Based on Spinal Cord Segments: A Preliminary Proof-of-Concept Study.

Objective: This study examined the activation difference of muscles innervated by cervical cord 5-6 (C5-C6) and cervical cord 8- thoracic cord 1 (C8-T1) in upper limb flexion synergy after stroke. Methods: Surface electromyography (sEMG) signals were collected during elbow flexion in stroke patients and healthy controls. The study compared normalized activation of two pairs of muscles that could cause similar joint movement but which dominated different spinal cord segments (clavicular part of the pectoralis major, PC vs. Sternocostal part of the pectoralis major, PS; Flexor carpi radialis, FCR vs. Flexor carpi ulnaris, FCU). In each muscle pair, one muscle was innervated by the same spinal cord segment (C5-C6), dominating the elbow flexion and the other was not. The comparison of the activation of the same muscle between patients and healthy controls was undertaken after standardization based on the activation of the biceps brachii in elbow flexion. Results: There was no difference between the PC and PS's normalized activation in healthy controls while the PC's normalized activation was higher than PS in stroke patients during elbow flexion. Similarly, there was no significant difference in normalized activation between FCR and FCU in healthy controls, and the same is true for stroke patients. However, the standardized activation of both FCR and FCU in stroke patients was significantly lower than that in healthy controls. Conclusion: After stroke, the activation of the distal muscles of the upper limb decreased significantly regardless of the difference of spinal cord segments; while the activation of the proximal muscles innervated by the same spinal cord segment (C5-C6) dominating the elbow flexion showed higher activation during flexion synergy. The difference in muscle activation based on spinal cord segments may be the reason for the stereotyped joint movement of upper limb flexion synergy.

PCR, in-situ hybridization, and phylogenetic analysis suggest that 'big belly' disease in barramundi, Lates calcarifer (Bloch), is caused by a novel Vibrio species.

'Big belly' disease is a chronic, granulomatous bacterial enteritis and peritonitis, first reported in 3- to 4-week-old Asian seabass or barramundi, Lates calcarifer Bloch fry. Affected fry are emaciated and have a swollen abdomen, and the condition is referred to as 'skinny pot-belly' or 'big belly' disease. In this study, histopathological examinations of diseased fish from a batch of 2-month-old, 6- to 8-cm L. calcarifer fingerlings, kept in seawater recirculating aquaculture systems, showed pathology resembling 'big belly' disease. Ethanol-fixed tissues were tested positive using specific PCR primers based on 16S rRNA genes. In situ hybridization using dioxygenin-labelled positive PCR products on formalin-fixed paraffin-embedded tissues showed positive reactions with intralesional, clusters of the large, 'big belly' coccobacilli. A phylogenetic tree constructed based on analyses of these 16S rRNA gene PCR products from five positive fish suggests that the 'big belly' bacterium is most likely a novel Vibrio species.

Scale Drop Disease Virus (SDDV) and Lates calcarifer Herpes Virus (LCHV) Coinfection Downregulate Immune-Relevant Pathways and Cause Splenic and Kidney Necrosis in Barramundi Under Commercial Farming Conditions.

Marine farming of barramundi (Lates calcarifer) in Southeast Asia is currently severely affected by viral diseases. To better understand the biological implications and gene expression response of barramundi in commercial farming conditions during a disease outbreak, the presence of pathogens, comparative RNAseq, and histopathology targeting multiple organs of clinically "sick" and "healthy" juveniles were investigated. Coinfection of scale drop disease virus (SDDV) and L. calcarifer herpes virus (LCHV) were detected in all sampled fish, with higher SDDV viral loads in sick than in healthy fish. Histopathology showed that livers in sick fish often had moderate to severe abnormal fat accumulation (hepatic lipidosis), whereas the predominant pathology in the kidneys shows moderate to severe inflammation and glomerular necrosis. The spleen was the most severely affected organ, with sick fish presenting severe multifocal and coalescing necrosis. Principal component analysis (PC1 and PC2) explained 70.3% of the observed variance and strongly associated the above histopathological findings with SDDV loads and with the sick phenotypes, supporting a primary diagnosis of the fish being impacted by scale drop disease (SDD). Extracted RNA from kidney and spleen of the sick fish were also severely degraded likely due to severe inflammation and tissue necrosis, indicating failure of these organs in advanced stages of SDD. RNAseq of sick vs. healthy barramundi identified 2,810 and 556 differentially expressed genes (DEGs) in the liver and muscle, respectively. Eleven significantly enriched pathways (e.g., phagosome, cytokine-cytokine-receptor interaction, ECM-receptor interaction, neuroactive ligand-receptor interaction, calcium signaling, MAPK, CAMs, etc.) and gene families (e.g., tool-like receptor, TNF, lectin, complement, interleukin, chemokine, MHC, B and T cells, CD molecules, etc.) relevant to homeostasis and innate and adaptive immunity were mostly downregulated in sick fish. These DEGs and pathways, also previously identified in L. calcarifer as general immune responses to other pathogens and environmental stressors, suggest a failure of the clinically sick fish to cope and overcome the systemic inflammatory responses and tissue degeneration caused by SDD.

Toward Genome-Based Selection in Asian Seabass: What Can We Learn From Other Food Fishes and Farm Animals?

Due to the steadily increasing need for seafood and the plateauing output of fisheries, more fish need to be produced by aquaculture production. In parallel with the improvement of farming methods, elite food fish lines with superior traits for production must be generated by selection programs that utilize cutting-edge tools of genomics. The purpose of this review is to provide a historical overview and status report of a selection program performed on a catadromous predator, the Asian seabass (Lates calcarifer, Bloch 1790) that can change its sex during its lifetime. We describe the practices of wet lab, farm and lab in detail by focusing onto the foundations and achievements of the program. In addition to the approaches used for selection, our review also provides an inventory of genetic/genomic platforms and technologies developed to (i) provide current and future support for the selection process; and (ii) improve our understanding of the biology of the species. Approaches used for the improvement of terrestrial farm animals are used as examples and references, as those processes are far ahead of the ones used in aquaculture and thus they might help those working on fish to select the best possible options and avoid potential pitfalls.

Early Post-Stroke Electroacupuncture Promotes Motor Function Recovery in Post-Ischemic Rats by Increasing the Blood and Brain Irisin.

OBJECTIVE: Recent studies have shown that irisin, a novel peptide hormone derived from muscles, could be used as a potential therapeutic drug against ischemic stroke. Moreover, electroacupuncture (EA) is widely used in the treatment of ischemic stroke. Yet, whether irisin is involved in the EA neuroprotection remains unclear. The following study investigated the association between serum and peri-lesional cortex irisin and EA-induced post-stroke motor recovery in rats. METHODS: The middle cerebral artery occlusion (MCAO) method was used to induce ischemic stroke in rats. Rats were randomly divided into two groups: a middle cerebral artery occlusion (MCAO) group (MCAO rats without treatment) and an electroacupuncture (EA) group (MCAO rats treated with EA). On the 3rd day post-stroke, infarct volume, behavioral deficits, surviving neurons, irisin protein expression in peri-infarction cortex, muscle tissue, and serum were evaluated to identify the neuroprotective of EA in acute ischemic stroke. RESULTS: Compared with the MCAO group, the EA group showed better behavioral performance, a smaller cerebral infarct volume, more surviving neurons, and a significant increase in irisin expression in the peri-infarction cortex and serum (p<0.05). However, no difference in irisin expression in the muscle tissue was found between the MCAO group and the EA group (p>0.05). CONCLUSION: EA promotes motor function recovery, reduces the volume of cerebral infarction, and alleviates neuronal death following ischemic stroke by enhancing the expression of irisin in both the blood and peri-lesional cortex.

An Enriched Environment Enhances Angiogenesis Surrounding the Cingulum in Ischaemic Stroke Rats.

An enriched environment (EE) has been demonstrated to improve functional recovery in animal models of ischaemic stroke through enhancing vascular endothelial growth factor- (VEGF-) mediated neuroprotection accompanied by angiogenesis in the ischaemic hemisphere. Whether EEs also promote VEGF-mediated neuroprotection and angiogenesis in the contralateral hemisphere remains unclear. Here, we explored the effect of EEs on VEGF expression and angiogenesis within the contralateral cerebral cortex in a rat middle cerebral artery occlusion/reperfusion (MCAO/r) model. We assessed the expression levels of platelet endothelial cell adhesion molecule-1 (CD31), VEGF, and endothelial nitric oxide synthase (eNOS) in the whole contralateral cerebral cortex using Western blotting assay but did not find an increase in the expression of CD31, VEGF, or eNOS in MCAO/r rats housed in EEs, which suggested that EEs did not enhance the overall expression of VEGF and eNOS or angiogenesis in the entire contralateral cortex. We further analysed the local effect of EEs by immunohistochemistry and found that in and around the bilateral cingulum in MCAO/r rats housed in EEs, haematopoietic progenitor cell antigen- (CD34-) positive endothelial progenitor cells were significantly increased compared with those of rats housed in standard cages (SCs). Further experiments showed that EEs increased neuronal VEGF expression surrounding the cingulum in MCAO/r rats and robustly upregulated eNOS expression. These results revealed that EEs enhanced angiogenesis, VEGF expression, and activation of the VEGF-eNOS pathway in and/or around the cingulum in MCAO/r rats, which were involved in the functional recovery of MCAO/r rats.

Differential Changed Excitability of Spinal Motor Neurons Innervating Tibialis Anterior and Peroneus Muscles Cause Foot Inversion After Stroke.

Objective: To study differential post-stroke changes of excitability of spinal motor neurons innervating a group of antagonist muscles of ankle and their effects on foot inversion. Methods: F waves in tibialis anterior (TA) and peroneus muscles (PN) were recorded. The condition of spasticity and foot inversion in stroke patients were also evaluated. The differences of F wave parameters between patients and healthy controls (HC), as well as TA and PN, were investigated. Results: There were natural differences in the persistence of the F waves (Fp) and F/M amplitude ratio (F/M) between TA and PN in HC. Stroke patients showed significantly higher F/M in TA and PN, while there was no difference in Fp comparing to HC. The natural differences in F wave parameters between TA and PN were differentially retained after stroke. The natural difference of the two muscles in Fp remained unchanged and the F/M difference disappeared in those without spasticity or foot inversion, while the Fp difference disappeared and the F/M difference remained in those with spasticity or foot inversion. Conclusion: Based on the natural difference of the number and size of spinal motor neurons innervating TA and PN, their excitability may change differently according to the severity of the stroke, which may be the reason of foot inversion.

Enriched Environment Promoted Cognitive Function via Bilateral Synaptic Remodeling After Cerebral Ischemia.

Ischemic stroke is the second leading cause of death worldwide. Ischemia-induced cognitive dysfunction may result in a poor quality of life. Synaptic plasticity plays a key role in cognition promotion. An enriched environment (EE), which can attenuate cognitive deficits in chronic cerebral hypoperfusion, has been shown to facilitate synaptic plasticity. However, the effect of EE on synaptic plasticity in bilateral cerebral hemispheres in stroke remains unclear. This study used a permanent middle cerebral artery occlusion mouse model, which was divided into standard housing and EE groups. The Morris water maze test was performed to detect the cognitive function. Electron microscopy was used to determine the synapse numbers. The expression of SYN and GAP-43 was then quantified by immunofluorescence staining and Western blot analysis. Compared with the standard housing, EE promoted the cognitive function recovery in the mice with stroke. Moreover, EE increased the synapse numbers and the expression of SYN and GAP-43 in both the ipsilateral and contralateral hemispheres (P < 0.05). A further correlation analysis revealed a positive correlation between the cognitive function outcomes and the relative expression of GAP-43 and SYN. Furthermore, the correlation of the expression of GAP-43 and SYN with cognitive function was higher in the contralateral brain than in the ipsilateral brain. In conclusion, an EE may promote cognitive function via bilateral synaptic remodeling after cerebral ischemia. Also, the contralateral brain may play an important role in the recovery of cognitive function.

CircTRNC18 inhibits trophoblast cell migration and epithelial-mesenchymal transition by regulating miR-762/Grhl2 pathway in pre-eclampsia.

Dysfunctions of epithelial-mesenchymal transition (EMT)-regulated cell migration and invasion have been involved in the pathogenesis of pre-eclampsia (PE). However, the role of circRNAs in EMT of PE has not been widely investigated. In this study, we identified that circTNRC18 was upregulated in PE placentas compared with normal pregnancy placentas. Moreover, circTNRC18 negatively regulated trophoblast cell migration and EMT. Overexpression of circTNRC18 reduced while depletion of circTNRC18 enhanced trophoblast cell migration and EMT. Mechanistically, circTNRC18 sponged miR-762 contributed to inhibit miR-762 activity and elevated EMT-related transcriptional factor Grhl2 protein level. miR-762 expression was lower in PE placentas and played a promoting role in trophoblast cell migration and EMT. In contrast, Grhl2 was highly expressed in PE placentas. Furthermore, we confirmed that upregulation of Grhl2 by circ-TNRC18-induced inhibition of miR-762 led to trophoblast cell migration and EMT. In conclusions, circTNRC18/miR-762/Grhl2 axis plays a key role in trophoblast cell migration and EMT. circTNRC18/miR-762/Grhl2 axis may be a potential therapeutic target in PE.

Enriched Environment Elicits Proangiogenic Mechanisms After Focal Cerebral Ischemia.

Brain has limited capacity for spontaneous recovery of lost function after stroke. Exposure to enriched environment (EE) can facilitate functional recovery, but mechanisms underlying this effect are poorly understood. Here, we used a middle cerebral artery occlusion (MCAO) model to investigate the impact of EE on angiogenesis in the post-ischemic brain in adult male Sprague Dawley rats, and examined whether blood-borne factors may contribute. Compared with standard cage (SC), exposure to EE was associated with greater improvement in neurological function, higher peri-infarct vascular density, and higher chronic post-ischemic cerebral blood flow assessed by laser speckle imaging. The effect persisted for at least 28 days. EE also enhanced the expression of hepatocyte growth factor in the peri-ischemic cortex when measured 15 days after MCAO. Interestingly, serum from rats exposed to EE after MCAO showed elevated levels of hepatocyte growth factor, and plasma or serum from rats exposed to EE after MCAO enhanced the survival and proliferation of cultured endothelial cells, in vitro, when compared with control plasma or serum from SC group after MCAO. Together, our data suggest that exposure to EE promotes angiogenesis in the ischemic brain that may in part be mediated by blood-borne factors.

A chromosome-level genome assembly of the Asian arowana, Scleropages formosus.

Asian arowana (Scleropages formosus), an ancient teleost belonging to the Order Osteoglossomorpha, has been a valuable ornamental fish with some varieties. However, its biological studies and breeding germplasm have been remarkably limited by the lack of a reference genome. To solve these problems, here we report high-quality genome sequences of three common varieties of Asian arowana (the golden, red and green arowana). We firstly generated a chromosome-level genome assembly of the golden arowana, on basis of the genetic linkage map constructed with the restriction site-associated DNA sequencing (RAD-seq). In addition, we obtained draft genome assemblies of the red and green varieties. Finally, we annotated 22,016, 21,256 and 21,524 protein-coding genes in the genome assemblies of golden, red and green varieties respectively. Our data were deposited in publicly accessible repositories to promote biological research and molecular breeding of Asian arowana.

Correction: Chromosomal-Level Assembly of the Asian Seabass Genome Using Long Sequence Reads and Multi-layered Scaffolding.

[This corrects the article DOI: 10.1371/journal.pgen.1005954.].