TFEB safeguards trophoblast syncytialization in humans and mice.

Nutrient sensing and adaptation in the placenta are essential for pregnancy viability and proper fetal growth. Our recent study demonstrated that the placenta adapts to nutrient insufficiency through mechanistic target of rapamycin (mTOR) inhibition-mediated trophoblast differentiation toward syncytiotrophoblasts (STBs), a highly specialized multinucleated trophoblast subtype mediating extensive maternal-fetal interactions. However, the underlying mechanism remains elusive. Here, we unravel the indispensable role of the mTORC1 downstream transcriptional factor TFEB in STB formation both in vitro and in vivo. TFEB deficiency significantly impaired STB differentiation in human trophoblasts and placenta organoids. Consistently, systemic or trophoblast-specific deletion of Tfeb compromised STB formation and placental vascular construction, leading to severe embryonic lethality. Mechanistically, TFEB conferred direct transcriptional activation of the fusogen ERVFRD-1 in human trophoblasts and thereby promoted STB formation, independent of its canonical function as a master regulator of the autophagy-lysosomal pathway. Moreover, we demonstrated that TFEB directed the trophoblast syncytialization response driven by mTOR complex 1 (mTORC1) signaling. TFEB expression positively correlated with the reinforced trophoblast syncytialization in human fetal growth-restricted placentas exhibiting suppressed mTORC1 activity. Our findings substantiate that the TFEB-fusogen axis ensures proper STB formation during placenta development and under nutrient stress, shedding light on TFEB as a mechanistic link between nutrient-sensing machinery and trophoblast differentiation.

Trophoblast PR-SET7 dysfunction induces viral mimicry response and necroptosis associated with recurrent miscarriage.

Recurrent miscarriage (RM) is a distressing pregnancy complication. While the etiology of RM remains unclear, growing evidence has indicated the relevance of trophoblast impairment to the pathogenesis of RM. PR-SET7 is the sole enzyme catalyzing monomethylation of H4K20 (H4K20me1) and has been implicated in many pathophysiological processes. However, how PR-SET7 functions in trophoblasts and its relevance to RM remain unknown. Here, we found that trophoblast-specific loss of Pr-set7 in mice led to defective trophoblasts, resulting in early embryonic loss. Mechanistic analysis revealed that PR-SET7 deficiency in trophoblasts derepressed endogenous retroviruses (ERVs), leading to double-stranded RNA stress and subsequent viral mimicry, which drove overwhelming interferon response and necroptosis. Further examination discovered that H4K20me1 and H4K20me3 mediated the inhibition of cell-intrinsic expression of ERVs. Importantly, dysregulation of PR-SET7 expression and the corresponding aberrant epigenetic modifications were observed in the placentas of RM. Collectively, our results demonstrate that PR-SET7 acts as an epigenetic transcriptional modulator essential for repressing ERVs in trophoblasts, ensuring normal pregnancy and fetal survival, which sheds new light on potential epigenetic causes contributing to RM.

Endogenous retrovirus-derived enhancers confer the transcriptional regulation of human trophoblast syncytialization.

Endogenous retroviruses (ERVs) have been proposed as a driving force for the evolution of the mammalian placenta, however, the contribution of ERVs to placental development and the underlying regulatory mechanism remain largely elusive. A key process of placental development is the formation of multinucleated syncytiotrophoblasts (STBs) in direct contact with maternal blood, through which constitutes the maternal-fetal interface critical for nutrient allocation, hormone production and immunological modulation during pregnancy. We delineate that ERVs profoundly rewire the transcriptional program of trophoblast syncytialization. Here, we first determined the dynamic landscape of bivalent ERV-derived enhancers with dual occupancy of H3K27ac and H3K9me3 in human trophoblast stem cells (hTSCs). We further demonstrated that enhancers overlapping several ERV families tend to exhibit increased H3K27ac and reduced H3K9me3 occupancy in STBs relative to hTSCs. Particularly, bivalent enhancers derived from the Simiiformes-specific MER50 transposons were linked to a cluster of genes important for STB formation. Importantly, deletions of MER50 elements adjacent to several STB genes, including MFSD2A and TNFAIP2, significantly attenuated their expression concomitant to compromised syncytium formation. Together, we propose that ERV-derived enhancers, MER50 specifically, fine-tune the transcriptional networks accounting for human trophoblast syncytialization, which sheds light on a novel ERV-mediated regulatory mechanism underlying placental development.

A new chromosome-scale duck genome shows a major histocompatibility complex with several expanded multigene families.

BACKGROUND: The duck (Anas platyrhynchos) is one of the principal natural hosts of influenza A virus (IAV), harbors almost all subtypes of IAVs and resists to many IAVs which cause extreme virulence in chicken and human. However, the response of duck's adaptive immune system to IAV infection is poorly characterized due to lack of a detailed gene map of the major histocompatibility complex (MHC). RESULTS: We herein reported a chromosome-scale Beijing duck assembly by integrating Nanopore, Bionano, and Hi-C data. This new reference genome SKLA1.0 covers 40 chromosomes, improves the contig N50 of the previous duck assembly with highest contiguity (ZJU1.0) of more than a 5.79-fold, surpasses the chicken and zebra finch references in sequence contiguity and contains a complete genomic map of the MHC. Our 3D MHC genomic map demonstrated that gene family arrangement in this region was primordial; however, families such as AnplMHCI, AnplMHCIIß, AnplDMB, NKRL (NK cell receptor-like genes) and BTN underwent gene expansion events making this area complex. These gene families are distributed in two TADs and genes sharing the same TAD may work in a co-regulated model. CONCLUSIONS: These observations supported the hypothesis that duck's adaptive immunity had been optimized with expanded and diversified key immune genes which might help duck to combat influenza virus. This work provided a high-quality Beijing duck genome for biological research and shed light on new strategies for AIV control.

SP1 impacts the primordial to primary follicle transition by regulating cholesterol metabolism in granulosa cells.

The primordial to primary follicle transition (PPT) in the ovary is critical to maintain sustainable reproductive resources in female mammals. However, it is unclear how granulosa cells (GCs) of the primary follicle participate in regulating PPT. This study focused on exploring the role of transcription factor Sp1 (SP1) in regulating PPT based on the fact that SP1 is pivotal for pregranulosa cell proliferation before primordial follicle formation. The results showed that mice fertility was prolonged when Sp1 was specifically depleted from GCs (GC- Sp1 -/- ). Besides, the PPT in GC- Sp1 -/- mice was reduced, resulting in more primordial follicles being preserved. Single-cell RNA-seq also indicated that the level of cholesterol metabolism was downregulated in GC- Sp1 -/- mice. Additionally, the PPT was promoted by either overexpression of ferredoxin-1 (FDX1), one of the key genes in mediating cholesterol metabolism or supplementing cholesterol for cultured fetal ovaries. Collectively, SP1 in GCs participates in the metabolism of cholesterol partially by regulating the transcription of Fdx1 during the PPT.

Paternal care plasticity: males care more for early- than late-developing embryos in an arboreal breeding treefrog.

BACKGROUND: Parental care benefits offspring but comes with costs. To optimize the trade-off of costs and benefits, parents should adjust care based on intrinsic and/or extrinsic conditions. The harm to offspring hypothesis suggests that parents should invest more in younger offspring than older offspring because younger offspring are more vulnerable. However, this hypothesis has rarely been comprehensively tested, as many studies only reveal an inverse correlation between parental care and offspring age, without directly testing the effects of offspring age on their vulnerability. To test this hypothesis, we studied Kurixalus eiffingeri, an arboreal treefrog with paternal care. We first performed a field survey by monitoring paternal care during embryonic development. Subsequently, we conducted a field experiment to assess the prevalence of egg predators (a semi-slug, Parmarion martensi) and the plasticity of male care. Finally, we conducted a laboratory experiment to assess how embryo age affects predation by P. martensi. RESULTS: Our results showed that (1) male attendance and brooding frequency affected embryo survival, and (2) males attended and brooded eggs more frequently in the early stage than in the late stage. The experimental results showed that (3) males increased attendance frequency when the predators were present, and (4) the embryonic predation by the semi-slug during the early was significantly higher than in the late stage. CONCLUSIONS: Our findings highlight the importance of paternal care to embryo survival, and the care behavior is plastic. Moreover, our results provide evidence consistent with the predictions of the harm to offspring hypothesis, as males tend to care more for younger offspring which are more vulnerable.

DPM2 serve as novel oncogene and prognostic marker transactivated by ESR1 in breast cancer.

Breast cancer (BRCA) is the most common malignancies worldwide with increasing rate. Dolichol phosphate mannose synthase (DPMS) is a critical mannosyltransferase involved in the posttranslational modification of proteins. At present, there is limited knowledge regarding the function of DPMS in breast cancer. In this study, silica analysis in multiple datasets found that dolichyl-phosphate mannosyltransferase subunit 2 (DPM2) is an unfavorable prognostic marker, suggesting its oncogenic role. Cell counting kit-8 and apoptosis assays show that DPM2-silenced cancer cells exhibit decreased growth potential and enhanced cell death rate. Further, transwell and wound healing assays show reduced invasion and migration capabilities in DPM2 knockdown groups, xenograft nude mice model demonstrated smaller tumor volume in DPM2 silenced BC cells. Then, the underlying downstream mechanism of DPM2 in BC was predicted and analyzed, highlighting classical tumorigenic pathways like JAK/STAT signaling pathway and oxidative phosphorylation activated in the cancer group. Finally, ChIP-seq analysis, expression correlation analysis, inhibitor treatment, and dual luciferase assays show that DPM2 is transcriptionally activated by estrogen receptor1 (ESR1). The results show that high expression of DPM2 mRNA is significantly correlated with shorter overall survival (OS) and disease-free survival (DFS) in breast cancer patients, and in vitro knockdown of DPM2 can significantly inhibit the malignant phenotypes of cells, including proliferation, invasion, migration, and apoptosis. These results suggest that DPM2 may play an important role in breast cancer. Altogether, we first uncovered the tumorigenic and prognostic role of DPM2 in breast cancer, cellular assays, and bioinformatics analysis highlighted DPM2 as oncogene via inhibited cancer-related signaling pathways in breast cancer. Besides, DPM2 is transcriptionally activated by ESR1, the signaling axis of ESR1/DPM2 provides a new strategy for BC-targeted therapy.

Identification of alternative splicing events related to fatty liver formation in duck using full-length transcripts.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of most common diseases in the world. Recently, alternative splicing (AS) has been reported to play a key role in NAFLD processes in mammals. Ducks can quickly form fatty liver similar to human NAFLD after overfeeding and restore to normal liver in a short time, suggesting that ducks are an excellent model to unravel molecular mechanisms of lipid metabolism for NAFLD. However, how alternative splicing events (ASEs) affect the fatty liver process in ducks is still unclear. RESULTS: Here we identify 126,277 unique transcripts in liver tissue from an overfed duck (77,237 total transcripts) and its sibling control (69,618 total transcripts). We combined these full-length transcripts with Illumina RNA-seq data from five pairs of overfed ducks and control individuals. Full-length transcript sequencing provided us with structural information of transcripts and Illumina RNA-seq data reveals the expressional profile of each transcript. We found, among these unique transcripts, 30,618 were lncRNAs and 1,744 transcripts including 155 lncRNAs and 1,589 coding transcripts showed significantly differential expression in liver tissues between overfed ducks and control individuals. We also detected 27,317 ASEs and 142 of them showed significant relative abundance changes in ducks under different feeding conditions. Full-length transcript profiles together with Illumina RNA-seq data demonstrated that 10 genes involving in lipid metabolism had ASEs with significantly differential abundance in normally fed (control) and overfed ducks. Among these genes, protein products of five genes (CYP4F22, BTN, GSTA2, ADH5, and DHRS2 genes) were changed by ASEs. CONCLUSIONS: This study presents an example of how to identify ASEs related to important biological processes, such as fatty liver formation, using full-length transcripts alongside Illumina RNA-seq data. Based on these data, we screened out ASEs of lipid-metabolism related genes which might respond to overfeeding. Our future ability to explore the function of genes showing AS differences between overfed ducks and their sibling controls, using genetic manipulations and co-evolutionary studies, will certainly extend our knowledge of genes related to the non-pathogenic fatty liver process.

Translocation of vaginal and cervical low-abundance non-Lactobacillus bacteria notably associate with endometriosis: A pilot study.

The etiology remains to be understood for endometriosis (EMS) which affected health negatively for 10% of reproductive-age women globally. Emerging studies found the associations of EMS with genital microbiota dysbiosis. However, the role of vaginal and cervical microbiota is not fully understood for Chinese women. This study recruited forty Chinese women (21 healthy women and 19 EMS patients) to analyze vaginal and cervical microbiota using 16S rRNA amplicon sequencing method. For both sites, there were no significant differences for distribution of microbial samples between control and EMS group, which was concordant with dominated Lactobacillus in both groups. In contrast, we observed accumulation of several low-abundance genera in vaginal and cervical microbiota of EMS patients, such as Fannyhessea, Prevotella, Streptococcus, Bifidobacterium, Veillonella, Megasphaera and Sneathia. Random forest analysis found that translocation of these genera had the significant importance in differentiating EMS patients from controls. In addition, cervix/vagina ratio of these genera also associated with EMS severity. And these genera had notable associations with ascending infection-related functional pathways, including flagellar assembly, bacterial motility proteins, bacterial toxins and epithelial cell signaling in Helicobacter pylori infection. These findings suggest that translocation of specific genera between vaginal and cervical sites play a role in EMS.

Comparative Analysis of Single-Path and Multipath Adrenal Venous Sampling in Primary Aldosteronism.

Objective: To evaluate the safety and efficacy of adrenal venous sampling (AVS) via the cubital vein and femoral vein synchronously. Methods: A total of 200 patients with primary aldosteronism admitted to the First Hospital of Fujian Medical University were enrolled and randomly divided into a single-path AVS group (SP, N = 108) and a multipath AVS group (MP, N = 92). We analyzed the clinical characteristics, intubation success rate, procedure cost, total fluoroscopy time, complications, contrast dosage, and the number of catheters selected during AVS. A planar quadrant system was established to mark the direction of the adrenal opening, with the intersection of the right renal vein and the inferior vena cava defined as the origin. In digital subtraction angiography images, the RAV opening located in the 0-3 o'clock direction was the first quadrant (I), and the 3-6 o'clock direction was the third quadrant (III). Results: There was no statistical difference between the two groups at baseline. Multipath AVS had a significantly higher success rate of right-sided intubation than single-path AVS (success rate of right-sided intubation/%: SP 87.96 vs MP 95.65, P = 0.043). Total fluoroscopy time was significantly reduced (fluoroscopy time/min: SP 9.80 ± 4.07 vs MP 7.42 ± 3.48, P = 0.024) and the cost of the procedure was markedly lower (cost/yuan: SP 3,900.93 ± 1,191.12 vs MP 3,378.26 ± 399.40, P < 0.001). There was no significant difference in postoperative complications between the two groups. In the group I, the procedure was completed mainly with an MPA catheter (catheter selection/%: MPA 98.19 vs TIG 17.65, P < 0.001). In the group III, TIG catheters were used more frequently (catheter selection/%: MPA 1.81 vs TIG 82.35, P < 0.001). Conclusion: Multipath AVS via the cubital vein and femoral vein improves the success rate of AVS with comparable safety compared to single-path AVS. When the RAV is opened in the III quadrant, the TIG catheter improves the cannulation success rate. The multipath AVS method provides more catheter options. Patients diagnosed with PA at the First Hospital of Fujian Medical University from December 2019 to December 2021 were included. The collection of medical records of the included population was approved by the ethics committee (approval number: [2021] 311). This was a cross-sectional study in which some patients were treated surgically and some were treated with superselective adrenal artery embolization (SAAE). We conducted a cohort study of patients treated with SAAE. ClinicalTrials.gov Protocol Registration and Results System (PRS) receipt release date: January 11, 2022. This trial is registered with NCT05188872.

Double-lung versus heart-lung transplantation for end-stage cardiopulmonary disease: a systematic review and meta-analysis.

We compared posttransplant outcomes following double-lung transplantation (DLTx) and heart-lung transplantation (HLTx), based on a search of PubMed, Cochrane Library, and Embase, from inception to March 8, 2022, for studies that report outcomes of these procedures. We then performed a meta-analysis of baseline characteristics and posttransplant outcomes. Subgroup analyses were implemented according to indication, publication year, and center. This study was registered on PROSPERO (number CRD42020223493). Ten studies were included in this meta-analysis, involving 1230 DLTx patients and 1022 HLTx patients. The DLTx group was characterized by older donors (P = 0.04) and a longer allograft ischemia time (P < 0.001) than the HLTx group. The two groups had comparable 1-year, 3-year, 5-year, 10-year survival rates (all P > 0.05), with similar results identified in subgroup analyses. We found no significant differences in 1-year, 5-year, and 10-year chronic lung allograft dysfunction (CLAD)-free survival, length of intensive care unit stay and hospital stay, length of postoperative ventilation, in-hospital mortality, or surgical complications between the groups (all P > 0.05). Thus, DLTx provides similar posttransplant survival to HLTx for end-stage cardiopulmonary disease. These two procedures have a comparable risk of CLAD and other posttransplant outcomes.

Floquet Superradiance Lattices in Thermal Atoms.

Floquet modulation has been widely used in optical lattices for coherent control of quantum gases, in particular for synthesizing artificial gauge fields and simulating topological matters. However, such modulation induces heating which can overwhelm the signal of quantum dynamics in ultracold atoms. Here we report that the thermal motion, instead of being a noise source, provides a new control knob in Floquet-modulated superradiance lattices, which are momentum-space tight-binding lattices of collectively excited states of atoms. The Doppler shifts combined with Floquet modulation provide effective forces along arbitrary directions in a lattice in frequency and momentum dimensions. Dynamic localization, dynamic delocalization, and chiral edge currents can be simultaneously observed from a single transport spectrum of superradiance lattices in thermal atoms. Our Letter paves a way for simulating Floquet topological matters in room-temperature atoms and facilitates their applications in photonic devices.

Insight on Efficacy of Renal Artery Denervation for Refractory Hypertension with Chronic Kidney Diseases: A Long-Term Follow-Up of 24-Hour Ambulatory Blood Pressure.

Aims: To explore the long-term efficacy and safety of renal denervation in patients with RHT and CKD, a post hoc analysis of eGFR subgroups was completed. Methods: Fifty-four patients with refractory hypertension with chronic kidney disease were treated with RDN and enrolled in the study. Patients were divided into three groups according to eGFR: eGFR 46-90 ml/min group, eGFR 15-45 ml/min group, and eGFR <15 ml/min group. The planned follow-up period was 48 months to assess 24 h ambulatory blood pressure, renal function, type of antihypertensive medication, and RDN complications. Results: The ablation sites of the GFR 46-90 ml/min group and GFR 15-45 ml/min group were 32.57 ± 2.99 and 29.53 ± 5.47, respectively. No complications occurred in the GFR 46-90 ml/min group. The GFR<15 ml/min group was treated with 27.07 ± 5.59 ablation. Renal artery dissection occurred in each group of GFR 15-45 ml/min and GFR <15 ml/min. And renal stent implantation artery was performed on these two patients. No severe renal artery stenosis occurred. There were no significant differences in Scr and eGFR between the three groups at each follow-up point. Compared with baseline, SBP was significantly of each group decreased to varying degrees at each follow-up time point. SBP decreased most in the GFR 46-90 ml/min group. Compared with baseline, the type of antihypertensive drugs used in the GFR46-90 ml/min group decreased significantly except for 36 and 48 months. At 48 months' postadmission, there was a significant decrease in the type of antihypertensive medication used in the GFR15-45 ml/min group, and there was no significant decrease in the type of antihypertensive medication used in the GFR<15 ml/min group. Conclusions: RDN can safely reduce SBP in CKD patients combined with RHT for 48 months, with the most pronounced reduction in the GFR15-45 ml/min group. The variety of antihypertensive drugs was significantly reduced after RDN. This was particularly evident in patients with GFR 15-45 ml/min.

Bone-targeting delivery of platelet lysate exosomes ameliorates glucocorticoid-induced osteoporosis by enhancing bone-vessel coupling.

BACKGROUND: Glucocorticoids (GCs) overuse is associated with decreased bone mass and osseous vasculature destruction, leading to severe osteoporosis. Platelet lysates (PL) as a pool of growth factors (GFs) were widely used in local bone repair by its potent pro-regeneration and pro-angiogenesis. However, it is still seldom applied for treating systemic osteopathia due to the lack of a suitable delivery strategy. The non-targeted distribution of GFs might cause tumorigenesis in other organs. RESULTS: In this study, PL-derived exosomes (PL-exo) were isolated to enrich the platelet-derived GFs, followed by conjugating with alendronate (ALN) grafted PEGylated phospholipid (DSPE-PEG-ALN) to establish a bone-targeting PL-exo (PL-exo-ALN). The in vitro hydroxyapatite binding affinity and in vivo bone targeting aggregation of PL-exo were significantly enhanced after ALN modification. Besides directly modulating the osteogenic and angiogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and endothelial progenitor cells (EPCs), respectively, PL-exo-ALN also facilitate their coupling under GCs' stimulation. Additionally, intravenous injection of PL-exo-ALN could successfully rescue GCs induced osteoporosis (GIOP) in vivo. CONCLUSIONS: PL-exo-ALN may be utilized as a novel nanoplatform for precise infusion of GFs to bone sites and exerts promising therapeutic potential for GIOP.

The E3 Ligase GmPUB21 Negatively Regulates Drought and Salinity Stress Response in Soybean.

E3-ubiquitin ligases are known to confer abiotic stress responses in plants. In the present study, GmPUB21, a novel U-box E3-ubiquitin ligase-encoding gene, was isolated from soybean and functionally characterized. The expression of GmPUB21, which possesses E3-ubiquitin ligase activity, was found to be significantly up-regulated by drought, salinity, and ABA treatments. The fusion protein GmPUB21-GFP was localized in the cytoplasm, nucleus, and plasma membrane. Transgenic lines of the Nicotiana benthamiana over-expressing GmPUB21 showed more sensitive to osmotic, salinity stress and ABA in seed germination and inhibited mannitol/NaCl-mediated stomatal closure. Moreover, higher reactive oxygen species accumulation was observed in GmPUB21 overexpressing plants after drought and salinity treatment than in wild-type (WT) plants. Contrarily, silencing of GmPUB21 in soybean plants significantly enhanced the tolerance to drought and salinity stresses. Collectively, our results revealed that GmPUB21 negatively regulates the drought and salinity tolerance by increasing the stomatal density and aperture via the ABA signaling pathway. These findings improved our understanding of the role of GmPUB21 under drought and salinity stresses in soybean.

Flat-Band Localization in Creutz Superradiance Lattices.

Flat bands play an important role in diffraction-free photonics and attract fundamental interest in many-body physics. Here we report the engineering of flat-band localization of collective excited states of atoms in Creutz superradiance lattices with tunable synthetic gauge fields. Magnitudes and phases of the lattice hopping coefficients can be independently tuned to control the state components of the flat band and the Aharonov-Bohm phases. We can selectively excite the flat band and control the flat-band localization with the synthetic gauge field. Our study provides a room-temperature platform for flat bands of atoms and holds promising applications in exploring correlated topological materials.

Hyperactivated Wnt-ß-catenin signaling in the absence of sFRP1 and sFRP5 disrupts trophoblast differentiation through repression of Ascl2.

BACKGROUND: Wnt signaling is a critical determinant for the maintenance and differentiation of stem/progenitor cells, including trophoblast stem cells during placental development. Hyperactivation of Wnt signaling has been shown to be associated with human trophoblast diseases. However, little is known about the impact and underlying mechanisms of excessive Wnt signaling during placental trophoblast development. RESULTS: In the present work, we observed that two inhibitors of Wnt signaling, secreted frizzled-related proteins 1 and 5 (Sfrp1 and Sfrp5), are highly expressed in the extraembryonic trophoblast suggesting possible roles in early placental development. Sfrp1 and Sfrp5 double knockout mice exhibited disturbed trophoblast differentiation in the placental ectoplacental cone (EPC), which contains the precursors of trophoblast giant cells (TGCs) and spongiotrophoblast cells. In addition, we employed mouse models expressing a truncated ß-catenin with exon 3 deletion globally and trophoblast-specifically, as well as trophoblast stem cell lines, and unraveled that hyperactivation of canonical Wnt pathway exhausted the trophoblast precursor cells in the EPC, resulting in the overabundance of giant cells at the expense of spongiotrophoblast cells. Further examination uncovered that hyperactivation of canonical Wnt pathway disturbed trophoblast differentiation in the EPC via repressing Ascl2 expression. CONCLUSIONS: Our investigations provide new insights that the homeostasis of canonical Wnt-ß-catenin signaling is essential for EPC trophoblast differentiation during placental development, which is of high clinical relevance, since aberrant Wnt signaling is often associated with trophoblast-related diseases.

Many-Body Chiral Edge Currents and Sliding Phases of Atomic Spin Waves in Momentum-Space Lattice.

Collective excitations (spin waves) of long-lived atomic hyperfine states can be synthesized into a Bose-Hubbard model in momentum space. We explore many-body ground states and dynamics of a two-leg momentum-space lattice formed by two coupled hyperfine states. Essential ingredients of this setting are a staggered artificial magnetic field engineered by lasers that couple the spin wave states and a state-dependent long-range interaction, which is induced by laser dressing a hyperfine state to a Rydberg state. The Rydberg dressed two-body interaction gives rise to a state-dependent blockade in momentum space and can amplify staggered flux-induced antichiral edge currents in the many-body ground state in the presence of magnetic flux. When the Rydberg dressing is applied to both hyperfine states, exotic sliding insulating and superfluid (supersolid) phases emerge. Because of the Rydberg dressed long-range interaction, spin waves slide along a leg of the momentum-space lattice without costing energy. Our study paves a route to the quantum simulation of topological phases and exotic dynamics with interacting spin waves of atomic hyperfine states in momentum-space lattice.

Identification and analysis of long non-coding RNAs in response to H5N1 influenza viruses in duck (Anas platyrhynchos).

BACKGROUND: Long non-coding RNAs (lncRNAs) are important component of mammalian genomes, where their numbers are even larger than that of protein-coding genes. For example, human (Homo sapiens) (96,308 vs. 20,376) and mouse (Mus musculus) (87,774 vs. 22,630) have more lncRNA genes than protein-coding genes in the NONCODEv5 database. Recently, mammalian lncRNAs were reported to play critical roles in immune response to influenza A virus infections. Such observation inspired us to identify lncRNAs related to immune response to influenza A virus in duck, which is the most important natural host of influenza A viruses. RESULTS: We explored features of 62,447 lncRNAs from human, mouse, chicken, zebrafish and elegans, and developed a pipeline to identify lncRNAs using the identified features with transcriptomic data. We then collected 151,970 assembled transcripts from RNA-Seq data of 21 individuals from three tissues and annotated 4094 duck lncRNAs. Comparing to duck protein-coding transcripts, we found that 4094 lncRNAs had smaller number of exons (2.4 vs. 10.2) and longer length of transcripts (1903.0 bp vs. 1686.9 bp) on average. Among them, 3586 (87.6%) lncRNAs located in intergenic regions and 619 lncRNAs showed differential expression in ducks infected by H5N1 virus when compared to control individuals. 58 lncRNAs were involved into two co-expressional modules related to anti-influenza A virus immune response. Moreover, we confirmed that eight lncRNAs showed remarkably differential expression both in vivo (duck individuals) and in vitro (duck embryo fibroblast cells, DEF cells) after infected with H5N1 viruses, implying they might play important roles in response to influenza A virus infection. CONCLUSIONS: This study presented an example to annotate lncRNA in new species based on model species using transcriptome data. These data and analysis provide information for duck lncRNAs' function in immune response to influenza A virus.

Prostaglandin-E2 deficiency during late pregnancy and the associated increase in interleukin-1ß derived from periaortic lymph nodes lead to abortion.

Prostaglandin E2 (PGE2) is a hormone with many physiological functions. During pregnancy, it is generally believed that there is a high level of PGE2 at the final stage of pregnancy, which induces the contraction of uterine smooth muscle and promotes the occurrence of childbirth. However, we find that high PGE2 levels are present throughout late pregnancy in mice, not just during childbirth, and that PGE2 deficiency induced by indomethacin during late pregnancy causes damage to the placental labyrinth and eventually leads to abortion. Interestingly, the damage is closely related to inflammation, which involves the role of inflammatory factors produced by the periaortic lymph nodes (PLNs) near the uterus. Further, through RNA sequencing, we reveal that PLNs produce a large amount of interleukin-1ß (IL-1ß) when exposed to PGE2 deficiency, which causes damage to the placental labyrinth, probably via destroying the extracellular matrix. Finally, events leading to abortion following indomethacin administration are effectively prevented by supplementing PGE2 or by PLN removal. These results suggest that high levels of PGE2 during late pregnancy protect fetuses from inflammatory damage related to IL-1ß. This work suggests a new role of PGE2 during late pregnancy and may provide potential therapeutic strategies for pathological pregnancy.