Porcine IKKε is involved in the STING-induced type I IFN antiviral response of the cytosolic DNA signaling pathway.

The cyclic GMP-AMP synthase and stimulator of interferon (IFN) genes (cGAS-STING) pathway serves as a crucial component of innate immune defense and exerts immense antiviral activity by inducing the expression of type I IFNs. Currently, STING-activated production of type I IFNs has been thought to be mediated only by TANK-binding kinase 1 (TBK1). Here, we identified that porcine IKKε (pIKKε) is also directly involved in STING-induced type I IFN expression and antiviral response by using IKKε-/- porcine macrophages. Similar to pTBK1, pIKKε interacts directly with pSTING on the C-terminal tail. Furthermore, the TBK1-binding motif of pSTING C-terminal tail is essential for its interaction with pIKKε, and within the TBK1-binding motif, the leucine (L) 373 is also critical for the interaction. On the other hand, both kinase domain and scaffold dimerization domain of pIKKε participate in the interactions with pSTING. Consistently, the reconstitution of pIKKε and its mutants in IKKε-/- porcine macrophages corroborated that IKKε and its kinase domain and scaffold dimerization domain are all involved in the STING signaling and antiviral function. Thus, our findings deepen the understanding of porcine cGAS-STING pathway, which lays a foundation for effective antiviral therapeutics against porcine viral diseases.

LiF/Li3N-Rich Electrode-Electrolyte Interfaces Enabled by Multi-Functional Electrolyte Additive to Achieve High-Performance Li/LiNi0.8Co0.1Mn0.1O2 Batteries.

LiPF6-based carbonate electrolytes have been extensively employed in commercial Li-ion batteries, but they face numerous interfacial stability challenges while applicating in high-energy-density lithium-metal batteries (LMBs). Herein, this work proposes N-succinimidyl trifluoroacetate (NST) as a multifunctional electrolyte additive to address these challenges. NST additive could optimize Li+ solvation structure and eliminate HF/H2O in the electrolyte, and preferentially be decomposed on the Ni-rich cathode (LiNi0.8Co0.1Mn0.1O2, NCM811) to generate LiF/Li3N-rich cathode-electrolyte interphase (CEI) with high conductivity. The synergistic effect reduces the electrolyte decomposition and inhibits the transition metal (TM) dissolution. Meanwhile, NST promotes the creation of solid electrolyte interphase (SEI) rich in inorganics on the Li metal anode (LMA), which restrains the growth of Li dendrites, minimizes parasitic reactions, and fosters rapid Li+ transport. As a result, compared with the reference, the Li/LiNi0.8Co0.1Mn0.1O2 cell with 1.0 wt.% NST exhibits higher capacity retention after 200 cycles at 1C (86.4% vs. 64.8%) and better rate performance, even at 9C. In the presence of NST, the Li/Li symmetrical cell shows a super-stable cyclic performance beyond 500 h at 0.5 mA cm-2/0.5 mAh cm-2. These unique features of NST are a promising solution for addressing the interfacial deterioration issue of high-capacity Ni-rich cathodes paired with LMA.

Bound states in the continuum in circular waveguides: toward the on-chip integration of nanofiber on silicon platform.

In previously reported researches on bound state in the continuum (BIC) waveguides, almost all of them are demonstrated with top-down fabrication procedures, leading to inconvenience for post-manipulation and size tuning. Nanofibers with circular cross sections are the fundamental components to transport energy due to their intrinsic advantages of high flexibility and adjustability, which is replaceable and can be readily manipulated over size and position on the substrate. In this work, we explore the possibility of achieving on-chip integration of silica nanofiber onto a silicon-on-insulator platform. By constructing additional leakage channels in coupled nanofiber waveguides, coherently destructive interferences are successfully achieved. The heavy leakage losses from the low-index nanofiber to a high-index silicon substrate are completely eliminated with BIC, and the propagation length of the nanofiber waveguide is significantly improved.

The Porcine and Chicken Innate DNA Sensing cGAS-STING-IRF Signaling Axes Exhibit Differential Species Specificity.

The innate immune DNA sensing cyclic GMP-AMP synthase (cGAS)-stimulator of IFN genes (STING) signaling pathway plays a key role in host antiviral function. Although the cGAS-STING pathway has been extensively studied, the cGAS-STING signaling in livestock and poultry is not well understood, and whether the species specificity exists is still unknown. In this study, we found that porcine and chicken STING, but not cGAS, exhibit species differences in regulation of IFN; that is, porcine (p)STING mediates good induction of IFN in mammalian cells and low IFN induction in chicken DF-1 cells; on the contrary, chicken (ch)STING mediates IFN induction only in chicken cells but not in mammalian cells. Furthermore, it was found that the motifs pLxIS of pSTING and pLxVS of chSTING are responsible for the species disparity, with the IFN activity of pSTING and chSTING exchanged by swapping the two pLxI/VS motifs. The pLxI/VS motifs mediated the interactions of various STING with downstream IFN regulatory factors (IRFs), reflecting the species-specific pIRF3 and chIRF7. Next, the STING, IRFs, and STING-IRFs were reconstituted in porcine and chicken macrophages that were genetically knocked out for STING and/or IRFs by the CRISPR-Cas9 approach. The results showed that pSTING plus pIRF3 or chIRF7 are able to induce IFN; however, chSTING plus chIRF7 but not pIRF3 are able to induce IFN, suggesting that pIRF3 is specific and stringent, which underlies the inability of chSTING to induce IFN in mammalian cells. In summary, our findings reveal the differential species specificity in the cGAS-STING pathway and the underlying mechanisms, thus providing valuable insights on the cGAS-STING-IRF signaling axis for comparative immunology.

Reduction-Tolerance Electrolyte Design for High-Energy Lithium Batteries.

Lithium batteries employing Li or silicon (Si) anodes hold promise for the next-generation energy storage systems. However, their cycling behavior encounters rapid capacity degradation due to the vulnerability of solid electrolyte interphases (SEIs). Though anion-derived SEIs mitigate this degradation, the unavoidable reduction of solvents introduces heterogeneity to SEIs, leading to fractures during cycling. Here, we elucidate how the reductive stability of solvents, dominated by the electrophilicity (EPT) and coordination ability (CDA), delineates the SEI formed on Li or Si anodes. Solvents exhibiting lower EPT and CDA demonstrate enhanced tolerance to reduction, resulting in inorganic-rich SEIs with homogeneity. Guided by these criteria, we synthesized three promising solvents tailored for Li or Si anodes. The decomposition of these solvents is dictated by their EPTs under similar solvation structures, imparting distinct characteristics to SEIs and impacting battery performance. The optimized electrolyte, 1 M lithium bis(fluorosulfonyl)imide (LiFSI) in N-Pyrrolidine-trifluoromethanesulfonamide (TFSPY), achieves 600 cycles of Si anodes with a capacity retention of 81 % (1910 mAh g-1). In anode-free Cu||LiNi0.5Co0.2Mn0.3O2 (NCM523) pouch cells, this electrolyte sustains over 100 cycles with an 82 % capacity retention. These findings illustrate that reducing solvent decomposition benefits SEI formation, offering valuable insights for the designing electrolytes in high-energy lithium batteries.

Atomic Engineering Modulates Oxygen Reduction of Hollow Carbon Matrix Confined Single Metal-Nitrogen Sites for Zinc-Air Batteries.

The systematical understanding of metal-dependent activity in electrocatalyzing oxygen reduction reaction (ORR), a vital reaction with sluggish kinetics for zinc-air batteries, remains quite unclear. An atomic and spatial engineering modulating ORR activity over hollow carbon quasi-sphere (HCS) confined in a series of single M-N (M = Cu, Mn, Ni) sites is reported here. Based on the theoretical prediction and experimental validation, Cu-N4 site with the lowest overpotential shows a better ORR kinetics than Mn-N4 and Ni-N4 . The ORR activity of single-atom Cu center can be further improved by decreasing the coordination number of N to two, namely Cu-N2 , due to the enhancement of electrons with lower coordination structure. Benefitting from the unique spatial confinement effect of the HCS structure in modulating electronic feature of active sites, the Cu-N2 site confined in HCS also delivers highly improved ORR kinetics and activity relative to that on planner graphene. Additionally, the best catalyst holds excellent promise in the application of zinc-air batteries. The findings will pave a new way to atomically and electronically tune active sites with high efficiency for other single-atom catalysts.

The Porcine Cyclic GMP-AMP Synthase-STING Pathway Exerts an Unusual Antiviral Function Independent of Interferon and Autophagy.

The innate immune DNA-sensing cyclic GMP-AMP synthase (cGAS)-stimulator of interferon (IFN) gene (STING) pathway exerts strong antiviral activity through downstream IFN production; however, it has been recently recognized that an IFN-independent activity of STING also plays an important role in antiviral functions. Nevertheless, the IFN-independent antiviral activity of STING is not fully understood. Here, we showed that porcine STING (pSTING) played a critical role against herpes simplex virus 1 (HSV-1) and vesicular stomatitis virus (VSV) infections, and IFN-defective mutants, including pSTING pLxIS sub, S365A, and △CTT, all exhibited similar antiviral functions, compared to wild-type (WT) pSTING. Furthermore, all of these IFN-defective pSTING mutants possessed comparable autophagy activity, relative to WT pSTING, as expected. From pSTING WT, S365A, and △CTT, the residues responsible for autophagy, including L333A/R334A, Y167A/L170A, and Y245A/L248A, were mutated. Surprisingly, all of these autophagy-defective pSTING mutants still resisted the two viral infections, demonstrating that the pSTING antiviral function is independent of IFN as well as autophagy. On the other hand, all of the autophagy-defective pSTING mutants triggered cell apoptosis, which was associated with and participated in the antiviral functions. Additionally, pSTING lost its antiviral activity in TANK-binding kinase 1 (TBK1)-/- and IFN regulatory factor 3 (IRF3)-/- porcine macrophages, indicating the involvement of TBK1 and IRF3 in other STING activities such as apoptosis. Collectively, our results revealed that STING exerts both IFN- and autophagy-independent antiviral activity, and they also suggested that STING-triggered cell apoptosis resists viral infections. IMPORTANCE The IFN-independent antiviral function of the cGAS-STING pathway has attracted great attention in recent years; however, the nature of this IFN-independent antiviral function is unknown, although STING-induced autophagy has been shown to mediate the STING antiviral activity. First, we analyzed the antiviral activity through the porcine cGAS-pSTING pathway and established that pSTING signaling exerts an IFN-independent antiviral function. Second, we found that pSTING-induced IFN-independent autophagy and the antiviral activity of pSTING are independent of both IFN and autophagy. Finally, pSTING signaling activates cell apoptosis independently of IFN and autophagy, and the apoptosis is associated with antiviral activity. Our results suggest that pSTING-activated apoptosis at least partially mediates the antiviral activity or multiple pSTING-activated signals, including IFN production, nuclear factor κ light chain enhancer of activated B cells (NF-κB) expression, autophagy, and apoptosis, exert a redundant antiviral role. Thus, the work reveals a new layer of complexity in STING antiviral activity.

Pseudomonas aeruginosa isolation is an important predictor for recurrent hemoptysis after bronchial artery embolization in patients with idiopathic bronchiectasis: a multicenter cohort study.

BACKGROUND: Nearly half of bronchiectasis patients receiving bronchial artery embolization (BAE) still have recurrent hemoptysis, which may be life-threatening. Worse still, the underlying risk factors of recurrence remain unknown. METHODS: A retrospective cohort was conducted of patients with idiopathic bronchiectasis who received BAE from 2015 to 2019 at eight centers. Patients were followed up for at least 24 months post BAE. Based on the outcomes of recurrent hemoptysis and recurrent severe hemoptysis, a Cox regression model was used to identify risk factors for recurrence. RESULTS: A total of 588 individuals were included. The median follow-up period was 34.0 months (interquartile range: 24.3-53.3 months). The 1-month, 1-year, 2-year, and 5-year cumulative recurrent hemoptysis-free rates were 87.2%, 67.5%, 57.6%, and 49.4%, respectively. The following factors were relative to recurrent hemoptysis: 24-h sputum volume (hazard ratio [HR] = 1.99 [95% confidence interval [95% CI]: 1.25-3.15, p = 0.015]), isolation of Pseudomonas aeruginosa (HR = 1.50 [95% CI: 1.13-2.00, p = 0.003]), extensive bronchiectasis (HR = 2.00 [95% CI: 1.29-3.09, p = 0.002]), and aberrant bronchial arteries (AbBAs) (HR = 1.45 [95% CI: 1.09-1.93, p = 0.014]). The area under the receiver operating characteristic curve of the nomogram was 0.728 [95% CI: 0.688-0.769]. CONCLUSIONS: Isolation of Pseudomonas aeruginosa is an important independent predictor of recurrent hemoptysis. The clearance of Pseudomonas aeruginosa might effectively reduce the hemoptysis recurrence rate.

Management of pulmonary arteriovenous malformations involves additional factors aside from the diameter of feeding arteries: a 3-year case-case retrospective analysis.

BACKGROUND: Pulmonary arteriovenous malformations (PAVMs) are rare but cause various manifestations. Although the diameter of feeding arteries has been linked to treatment decisions, relationships among the characteristics of PAVMs, clinical symptoms, and treatment effect remain unclear. The present study was performed to investigate how collective characteristics of PAVMs relate to clinical symptoms and to provide proper treatment recommendations for patients with PAVMs. METHODS: We retrospectively analysed 838,447 patients' radiographic data and medical records from January 2018 to December 2020. Patients were included if a PAVM was radiographically detected for the first time in our hospital. Ordered multivariable logistic regression and hierarchical multiple regression were performed to analyse the relationships between characteristics of PAVMs and various clinical symptoms. We investigated the management of PAVMs in four tertiary university hospitals. RESULTS: Detection rate of PAVMs was 0.025% (207/838,447), and 37.6% of patients (78/207) also had hereditary haemorrhagic telangiectasia. Eight patients were diagnosed with bilateral diffuse PAVMs. Two hundred thirty-six lesions were detected in 199 patients, and the mean diameter of the feeding artery was 4.13 ± 1.92 mm. Most PAVMs were the simple type and located in the peripheral pulmonary area. In total, 34.3% of patients (71/207) were symptom-free; remaining patients showed various manifestations, and respiratory symptoms were most common (dyspnoea on exertion, 47.8%). The diameter of the feeding artery and the type and the number of PAVMs were correlated with hypoxaemia (P < 0.001, P < 0.001, and P = 0.037, respectively). The collective characteristics of PAVMs were not related to the severity of central nervous system symptoms (largest diameter of feeding artery, P = 0.8; largest diameter of sac, P = 0.42; number of PAVMs, P = 0.35; type of PAVMs, P = 0.99). Various symptoms were greatly relieved after treatment. The hospital investigation showed that management of PAVMs was not generally appreciated in clinical practice. CONCLUSIONS: Our study revealed a low detection rate of PAVMs and a low degree of association with hereditary haemorrhagic telangiectasia in the general population. Considering the connection between collective characteristics of PAVMs and various clinical symptoms, clinicians should consider the type and number of PAVMs, the largest diameter of the feeding artery, and clinical symptoms when managing patients with PAVMs.

Transcriptome analysis of immune-related genes in Sesarmops sinensis hepatopancreas in reaction to peptidoglycan challenge.

Sesarmops sinensis is a dominant omnivorous crab species, which plays an important ecological function in salt marsh ecosystems. To better understand its immune system and immune related genes under pathogen infection, the transcriptome was analyzed by comparing the data of S. sinensis hepatopancreas stimulated by PBS and PGN. A set of assembly and annotation identified 39,039 unigenes with an average length of 1105 bp, obtaining 1300 differentially expressed genes (DEGs) in all, which included 466 remarkably up-regulated unigenes and 834 remarkably down-regulated unigenes. In addition, based on mensurable real time-polymerase chain reaction and high-throughput sequencing, several immune responsive genes were found to be markedly up-regulated under PGN stimulation. In conclusion, in addition to enriching the existing transcriptome data of S. sinensis, this study also clarified the immune response of S. sinensis to PGN stimulation, which will help us to further understand the crustacean's immune system.

A complement factor I (CFI) gene mediates innate immune responses in yellow catfish Pelteobagrus fulvidraco.

This study isolated CFI gene from Pelteobagrus fulvidraco and named it PfCFI. The cDNA of PfCFI is 2374 bp long, including a 52 bp 5' untranslated sequence, a 222 bp 3' untranslated sequence, and an open reading frame (ORF) of 2100 bp encoding polypeptide consisting of 699 amino acids. Phylogenetic analysis revealed that the PfCFI was closely related to CFI of Ictalurus punctatus. Real-time quantitative reverse transcription-PCR (qRT-PCR) analysis indicate that there is the PfCFI gene which expressed in all the rest of tested tissues in varied levels, and mainly distributed in liver and least in heart. The reseachers induce the expressions level of PfCFI gene in liver, spleen, head kidney and blood at different points in time after challenged with lipopolysaccharide (LPS), and polyriboinosinic polyribocytidylic acid (poly I:C), respectively. Together these results suggested that CFI gene plays an important role in resistance to pathogens in yellow catfish immunity.

Pramipexole attenuates 6-OHDA-induced Parkinson's disease by mediating the Nurr1/NF-κB pathway.

Neuroinflammation is the key factor associated with the progression of Parkinson's disease (PD). Pramipexole (PPX) has anti-inflammatory and antioxidant properties. This study explored the effects of PPX on PD and its related mechanisms. A PD rat model was established using 6-hydroxydopamine (6-OHDA). Thirty rats were divided into the following three groups: control, PD, and PD + PPX. The rats in the PD and PD + PPX groups were first administered 6-OHDA and then respectively treated with saline and PPX. Afterward, rotational behavior tests were performed to evaluate the efficiency of PPX. The level of tyrosine hydroxylase (TH) was measured using immunohistochemical staining. Subsequently, real-time quantitative PCR (RT-qPCR) and western blot were used to determine the expression of α-synuclein (α-syn), nuclear receptor subfamily 4 group A member 2 (Nurr1), and nuclear factor kappa B (NF-κB). PPX improved the motor behavior of PD rats caused by 6-OHDA. The number of TH-positive neurons in the PD group was significantly lower than that in the control group (P < 0.05), while PPX could rescue 6-OHDA-induced TH loss. RT-qPCR and western blot showed that Nurr1 expression was significantly downregulated in the PD group compared to that of the control group (P < 0.05), while after PPX treatment, its expression was significantly upregulated (P < 0.05). For α-syn and NF-κB, 6-OHDA significantly upregulated their expressions (P < 0.05), whereas PPX reversed them. PPX improved the motor behavior of PD through mediating the inflammatory response and regulating the Nurr1/NF-κB signaling pathway.

Massive haemorrhagic complications of ruptured pulmonary arteriovenous malformations: outcomes from a 12 years' retrospective study.

BACKGROUND: The life-threatening haemorrhagic complications of pulmonary arteriovenous malformations (PAVMs) are extremely rare, and only described in isolated cases. This study was designed to comprehensively investigate management of ruptured PAVMs. METHODS: We retrospectively assessed clinical and imaging data of ruptured PAVMs to summarize incidence, clinical characteristics, and outcomes following embolisation between January 2008 and January 2021. RESULTS: Eighteen of 406 (4.4%) patients with PAVMs developed haemorrhagic complications. Twelve of 18 patients were clinically diagnosed with hereditary haemorrhagic telangiectasia (HHT). Haemorrhagic complications occurred with no clear trigger in all cases. Eight of 18 patients (44.4%) were initially misdiagnosed or had undergone early ineffective treatment. 28 lesions were detected, with 89.3% of them located in peripheral lung. Computed tomography angiography (CTA) showed indirect signs to indicate ruptured PAVMs in all cases. Lower haemoglobin concentrations were associated with the diameter of afferent arteries in the ruptured lesions. Successful embolotherapy was achieved in all cases. After embolotherapy, arterial oxygen saturation improved and bleeding was controlled (P < 0.05). The mean follow-up time was 3.2 ± 2.5 years (range, 7 months to 10 years). CONCLUSIONS: Life threatening haemorrhagic complications of PAVMs are rare, they usually occur without a trigger and can be easily misdiagnosed. HHT and larger size of afferent arteries are major risk factors of these complications. CTA is a useful tool for diagnosis and therapeutic guidance for ruptured PAVMs. Embolotherapy is an effective therapy for this life-threatening complication.

Genome-Scale Expression Pattern of Long Non-Coding RNAs in Chinese Uyghur Patients with Parkinson's Disease.

BACKGROUND Long non-coding RNAs (lncRNAs) are transcripts thought to regulate gene expression at the post-transcriptional level. Some lncRNAs are associated with Parkinson's disease (PD) and participate in pathological processes of PD. The incidence of PD is relatively high in members of the Uyghur minority living in Xingjiang province of China. This study measured the expression of lncRNAs in the peripheral blood cells of Chinese Uyghur individuals with and without PD and analyzed the possible function of these lncRNAs in the development of PD. MATERIAL AND METHODS Peripheral blood samples were collected from 55 Uyghur patients with PD and 55 healthy volunteers. Total RNA was extracted, and the levels of expression of whole-genome lncRNAs and mRNAs in 10 samples (5 PD and 5 controls) were determined by microarray method. The expression levels of lncRNAs in all 100 subjects were determined by qRT-PCR. The lncRNA expression profiles of PD patients were determined based on lncRNA microarray chip analysis, and differentially expressed lncRNAs were identified. The results of chip analysis were confirmed in a large clinical cohort. RESULTS Comparison of subjects with and without PD identified 32 significantly up-regulated and 18 significantly down-regulated lncRNAs in the PD group. GO analysis showed that mRNAs encoding proteins involved in the regulation of biological processes were differentially expressed, with the inflammatory immune response being the most significantly related pathway. CONCLUSIONS The expression of lncRNAs in peripheral blood differed significantly in PD patients and controls. These differentially expressed lncRNAs may play a role in the development of PD.

Role of TRPP2 in mouse airway smooth muscle tension and respiration.

The transient receptor potential polycystin-2 (TRPP2) is encoded by the Pkd2 gene, and mutation of this gene can cause autosomal dominant polycystic kidney disease (ADPKD). Some patients with ADPKD experience extrarenal manifestations, including radiologic and clinical bronchiectasis. We hypothesized that TRPP2 may regulate airway smooth muscle (ASM) tension. Thus, we used smooth muscle-Pkd2 conditional knockout (Pkd2SM-CKO) mice to investigate whether TRPP2 regulated ASM tension and whether TRPP2 deficiency contributed to bronchiectasis associated with ADPKD. Compared with wild-type mice, Pkd2SM-CKO mice breathed more shallowly and faster, and their cross-sectional area ratio of bronchi to accompanying pulmonary arteries was higher, suggesting that TRPP2 may regulate ASM tension and contribute to the occurrence of bronchiectasis in ADPKD. In a bioassay examining isolated tracheal ring tension, no significant difference was found for high-potassium-induced depolarization of the ASM between the two groups, indicating that TRPP2 does not regulate depolarization-induced ASM contraction. By contrast, carbachol-induced contraction of the ASM derived from Pkd2SM-CKO mice was significantly reduced compared with that in wild-type mice. In addition, relaxation of the carbachol-precontracted ASM by isoprenaline, a ß-adrenergic receptor agonist that acts through the cAMP/adenylyl cyclase pathway, was also significantly attenuated in Pkd2SM-CKO mice compared with that in wild-type mice. Thus, TRPP2 deficiency suppressed both contraction and relaxation of the ASM. These results provide a potential target for regulating ASM tension and for developing therapeutic alternatives for some ADPKD complications of the respiratory system or for independent respiratory disease, especially bronchiectasis.

A non-mammalian Toll-like receptor 26 (TLR26)gene mediates innate immune responses in yellow catfish Pelteobagrus fulvidraco.

In this study, we identified a fish-specific Toll-like receptor (TLR) in Pelteobagrus fulvidraco, an economically important freshwater fish in China. This TLR, PfTLR26, was shown to be encoded by a 3084 bp open reading frame (ORF), producing a polypeptide 1027 amino acids in length. The PfTLR26 protein contains a signal peptide, eight leucine-rich repeat (LRR) domains, two LRR_TYP domains in the extracellular region, and a Toll/interleukin (IL)-1 receptor (TIR) domain in the cytoplasmic region, consistent with the characteristic TLR domain architecture. This predicted 117.1 kDa protein was highly homologous to those of other fish, with phylogenetic analysis revealing the closest relation to TLR26 of Ictalurus punctatus. Real-time quantitative reverse transcription-PCR (qRT-PCR) analysis showed that the PfTLR26 gene was expressed in all tissues tested, with the highest expression levels seen in the head kidney and blood, and the lowest seen in muscle. PfTLR26 exhibited significant upregulation in liver, spleen, head kidney, and blood at different time points following challenge with the common TLR agonists lipopolysaccharide (LPS) and polyriboinosinic polyribocytidylic acid (Poly I:C). Taken together, these results suggest that PfTLR26 may be an important component of the P. fulvidraco innate immune system, participating in the transduction of TLR signaling under pathogen stimulation.

Bilateral pulmonary vein stenting for treatment of massive hemoptysis caused by pulmonary vein stenosis following catheter ablation for atrial fibrillation.

BACKGROUND: Massive hemoptysis is a life-threatening condition. Massive hemoptysis caused by pulmonary vein stenosis (PVS) after radiofrequency catheter ablation for atrial fibrillation (AF) is rare. However, bilateral lung hemorrhage following bilateral PVS is extremely rare. CASE PRESENTATION: We herein describe a 62-year-old man with refractory massive hemoptysis after radiofrequency catheter ablation for AF, which was successfully controlled by surgical lobectomy and endovascular bilateral PV stenting. The hemorrhage was derived from the bilateral lungs following PV obstruction and bilateral PVS, which was definitively diagnosed by bronchoscopic examination. The patient had no recurrence of hemoptysis during a follow-up period of 30 months, and the PV stents had not narrowed as shown by computed tomography 30 months after stent placement. CONCLUSIONS: Massive hemoptysis can be caused by bilateral PVS after radiofrequency catheter ablation for AF, and hemorrhage from the bilateral lungs in such patients is extremely rare. Nevertheless, cardiologists, interventional radiologists, and pulmonologists should consider the potential for massive hemoptysis caused by PVS.

Transcriptomic analysis of immune-related genes in the lipopolysaccharide-stimulated hepatopancreas of the mudflat crab Helice tientsinensis.

The mudflat crab Helice tientsinensis is one of the most economically important aquaculture species in China. Nevertheless, it is susceptible to various diseases caused by viruses, bacteria and rickettsia-like organisms. A better understanding of the immune system and genes related to the responses to bacterial and viral infection is required. Herein, the hepatopancreas transcriptome of H. tientsinensis was analyzed by comparing control and lipopolysaccharide (LPS)-stimulated RNA-Seq data, yielding 91,885,038 bp and 13.78 Gb of clean reads. Following assembly and annotation, 93,207 unigenes with an average length of 883 bp were identified, of which 31,674 and 13,700 were annotated in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, respectively. Following LPS, 4845 differentially expressed genes (DEGs) were identified, of which 2491 and 2354 were up- and down-regulated, respectively. To further investigate immune-related DEGs, KEGG enrichment analysis identified immune response pathways, most notably the peroxisome and Toll-like receptor signaling pathways. Quantitative real time-PCR (qRT-PCR) confirmed the up-regulation of a random selection of DEGs. This systematic transcriptomic analysis of the innate immune pathway in H. tientsinensis expands our understanding of the immune system in crabs.

De novo transcriptome assembly and analysis of differential gene expression following lipopolysaccharide challenge in Pelteobagrus fulvidraco.

The yellow catfish, Pelteobagrus fulvidraco, has been recognized as an important freshwater aquaculture species in Eastern and Southeast Asia. To gain a better understanding of the immune response in P. fulvidraco, we analyzed its transcriptome following stimulation with lipopolysaccharide (LPS). Phosphate buffer saline (PBS) was used as control. Following assembly and annotation, 72,152 unigenes with an average length of 1090 bp were identified. A total of 370 differentially expressed genes (DEGs) in the P. fulvidraco were observed at 12 h post LPS treatment, including 197 up-regulated genes and 173 down-regulated genes. Clusters of Orthologous Groups of proteins (KOG/COG) annotation demonstrated that a total of 18,819 unigenes classified into 26 categories. Gene ontology (GO) analysis revealed 20 biological process subcategories, 7 cellular component subcategories and 20 molecular function subcategories. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis identified immune responses pathways. Quantitative reverse transcription polymerase chain reaction measured the expression of 18 genes involved in the immune response. CXCL2-like chemokine (CXCL2), goose-type lysozyme (LYZ G), and cathepsin K (CTSK) were significantly up-regulated. This study enriches the P. fulvidraco transcriptome database and provides insight into the immune response of P. fulvidraco against infection.

cDNA cloning and expression analysis of a hepcidin gene from yellow catfish Pelteobagrus fulvidraco (Siluriformes: Bagridae).

Hepcidin is a small, cysteine-rich antimicrobial peptide with a highly conserved ß-sheet structure that plays a vital role in innate host immunity against pathogenic organisms. In this study, a hepcidin gene was identified in Pelteobagrus fulvidraco, an economically important freshwater fish in China. The gene is named PfHep. The complete PfHep cDNA was 723 bp, including a 5'-untranslated region (UTR) of 102 bp, a 3'-UTR of 339 bp and an open reading frame of 282 bp encoding a polypeptide of 93 amino acids, which includes a predicted signal peptide and the Hepcidin domain. The predicted mature, cationic PfHep protein has a typical hepcidin RX (K/R)R motif and eight conserved cysteine residues. The deduced PfHep protein sequence has 70%, 54% and 39% percent identity with hepcidins from Ictalurus punctatus, Danio rerio, and Homo sapiens, respectively. The predicted tertiary structure of PfHep is very similar to that of hepcidin in other animals. Phylogenetic analysis revealed that PfHep is closely related to the hepcidins of I. punctatus and I. furcatus. Real-time quantitative reverse transcription-PCR showed that the PfHep gene was expressed most in liver of healthy P. fulvidraco, and expressed to some extent in all the tissues tested. After challenge with lipopolysaccharide and polyriboinosinic:polyribocytidylic acid (poly I:C), respectively, the expression levels of PfHep were markedly upregulated in liver, spleen, head kidney and blood at different time points. Together these results imply that PfHep may be an important component of the innate immune system and be involved in immune defense against invading pathogens.