Cryo-EM structure of ACE2-SIT1 in complex with tiagabine.

The pharmacology of amino acid transporters in the SLC6 family is poorly developed compared to that of the neurotransmitter transporters. To identify new inhibitors of the proline transporter SIT1 (SLC6A20), its expression in Xenopus laevis oocytes was optimized. Trafficking of SIT1 was augmented by co-expression of angiotensin-converting enzyme 2 (ACE2) in oocytes but there was no strict requirement for co-expression of ACE2. A pharmacophore-guided screen identified tiagabine as a potent non-competitive inhibitor of SIT1. To understand its binding mode, we determined the cryo-electron microscopy (cryo-EM) structure of ACE2-SIT1 bound with tiagabine. The inhibitor binds close to the orthosteric proline binding site, but due to its size extends into the cytosolic vestibule. This causes the transporter to adopt an inward-open conformation, in which the intracellular gate is blocked. This study provides the first structural insight into inhibition of SIT1 and generates tools for a better understanding of the ACE2-SIT1 complex. These findings may have significance for SARS-CoV-2 binding to its receptor ACE2 in human lung alveolar cells where SIT1 and ACE2 are functionally expressed.

Oncolytic strategy using new bifunctional HDACs/BRD4 inhibitors against virus-associated lymphomas.

Primary effusion lymphoma (PEL) caused by Kaposi sarcoma-associated herpesvirus (KSHV) is an aggressive malignancy with poor prognosis even under chemotherapy. Currently, there is no specific treatment for PEL therefore requiring new therapies. Both histone deacetylases (HDACs) and bromodomain-containing protein 4 (BRD4) have been found as therapeutic targets for PEL through inducing viral lytic reactivation. However, the strategy of dual targeting with one agent and potential synergistic effects have never been explored. In the current study, we first demonstrated the synergistic effect of concurrently targeting HDACs and BRD4 on KSHV reactivation by using SAHA or entinostat (HDACs inhibitors) and (+)-JQ1 (BRD4 inhibitor), which indicated dual blockage of HDACs/BRD4 is a viable therapeutic approach. We were then able to rationally design and synthesize a series of new small-molecule inhibitors targeting HDACs and BRD4 with a balanced activity profile by generating a hybrid of the key binding motifs between (+)-JQ1 and entinostat or SAHA. Upon two iterative screenings of optimized compounds, a pair of epimers, 009P1 and 009P2, were identified to better inhibit the growth of KSHV positive lymphomas compared to (+)-JQ1 or SAHA alone at low nanomolar concentrations, but not KSHV negative control cells or normal cells. Mechanistic studies of 009P1 and 009P2 demonstrated significantly enhanced viral reactivation, cell cycle arrest and apoptosis in KSHV+ lymphomas through dually targeting HDACs and BRD4 signaling activities. Importantly, in vivo preclinical studies showed that 009P1 and 009P2 dramatically suppressed KSHV+ lymphoma progression with oral bioavailability and minimal visible toxicity. These data together provide a novel strategy for the development of agents for inducing lytic activation-based therapies against these viruses-associated malignancies.

A nanopore-based cucumber genome assembly reveals structural variations at two QTLs controlling hypocotyl elongation.

The Xishuangbanna (XIS) cucumber (Cucumis sativus var. xishuangbannanesis) is a semiwild variety that has many distinct agronomic traits. Here, long reads generated by Nanopore sequencing technology helped assembling a high-quality genome (contig N50 = 8.7 Mb) of landrace XIS49. A total of 10,036 structural/sequence variations (SVs) were identified when comparing with Chinese Long (CL), and known SVs controlling spines, tubercles, and carpel number were confirmed in XIS49 genome. Two QTLs of hypocotyl elongation under low light, SH3.1 and SH6.1, were fine-mapped using introgression lines (donor parent, XIS49; recurrent parent, CL). SH3.1 encodes a red-light receptor Phytochrome B (PhyB, CsaV3_3G015190). A ∼4 kb region with large deletion and highly divergent regions (HDRs) were identified in the promoter of the PhyB gene in XIS49. Loss of function of this PhyB caused a super-long hypocotyl phenotype. SH6.1 encodes a CCCH-type zinc finger protein FRIGIDA-ESSENTIAL LIKE (FEL, CsaV3_6G050300). FEL negatively regulated hypocotyl elongation but it was transcriptionally suppressed by long terminal repeats retrotransposon insertion in CL cucumber. Mechanistically, FEL physically binds to the promoter of CONSTITUTIVE PHOTOMORPHOGENIC 1a (COP1a), regulating the expression of COP1a and the downstream hypocotyl elongation. These above results demonstrate the genetic mechanism of cucumber hypocotyl elongation under low light.

Biological characteristics of mechanosensitive channels MscS and MscL in Actinobacillus pleuropneumoniae.

Actinobacillus pleuropneumoniae is an important respiratory pathogen that can cause porcine contagious pleuropneumonia (PCP), resulting in significant economic losses in swine industry. Microorganisms are subjected to drastic changes in environmental osmolarity. In order to alleviate the drastic rise or fall of osmolarity, cells activate mechanosensitive channels MscL and MscS through tension changes. MscL not only regulates osmotic pressure but also has been reported to secrete protein and uptake aminoglycoside antibiotic. However, MscL and MscS, as the most common mechanosensitive channels, have not been characterized in A. pleuropneumoniae. In this study, the osmotic shock assay showed that MscL increased sodium adaptation by regulating cell length. The results of MIC showed that deletion of mscL decreased the sensitivity of A. pleuropneumoniae to multiple antibiotics, while deletion of mscS rendered A. pleuropneumoniae hypersensitive to penicillin. Biofilm assay demonstrated that MscL contributed the biofilm formation but MscS did not. The results of animal assay showed that MscL and MscS did not affect virulence in vivo. In conclusion, MscL is essential for sodium hyperosmotic tolerance, biofilm formation, and resistance to chloramphenicol, erythromycin, penicillin, and oxacillin. On the other hand, MscS is only involved in oxacillin resistance.IMPORTANCEBacterial resistance to the external environment is a critical function that ensures the normal growth of bacteria. MscL and MscS play crucial roles in responding to changes in both external and internal environments. However, the function of MscL and MscS in Actinobacillus pleuropneumoniae has not yet been reported. Our study shows that MscL plays a significant role in osmotic adaptation, antibiotic resistance, and biofilm formation of A. pleuropneumoniae, while MscS only plays a role in antibiotic resistance. Our findings provide new insights into the functional characteristics of MscL and MscS in A. pleuropneumoniae. MscL and MscS play a role in antibiotic resistance and contribute to the development of antibiotics for A. pleuropneumoniae.

Foxp2 deficiency impairs reproduction by modulating the hypothalamic-pituitary-gonadal axis in zebrafish†.

FOXP2 was initially characterized as a transcription factor linked to speech and language disorders. Single-cell RNA sequencing reveals that Foxp2 is enriched in the gonadotrope cluster of the pituitary gland and colocalized with the hormones LHB and FSHB in chickens and mice, implying that FOXP2 might be associated with reproduction in vertebrates. Herein, we investigated the roles of foxp2 in reproduction in a Foxp2-deficient zebrafish model. The results indicated that the loss of Foxp2 inhibits courtship behavior in adult male zebrafish. Notably, Foxp2 deficiency disrupts gonad development, leading to retardation of follicle development and a decrease in oocytes in females at the full-growth stage, among other phenotypes. The transcriptome analysis (RNA-seq) also revealed that differentially expressed genes clustered into the estrogen signaling and ovarian steroidogenesis-related signaling pathways. In addition, we found that Foxp2 deficiency could modulate the hypothalamic-pituitary-gonadal axis, especially the regulation of lhb and fshb expression, in zebrafish. In contrast, the injection of human chorionic gonadotropin, a specific LH agonist, partially rescues Foxp2-impaired reproduction in zebrafish, suggesting that Foxp2 plays an important role in the regulation of reproduction via the hypothalamic-pituitary-gonadal axis in zebrafish. Thus, our findings reveal a new role for Foxp2 in the regulation of reproduction in vertebrates.

Role of lymphatic endothelium specific hyaluronan receptor 1 in virus infection and associated diseases.

Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) serves as a prominent marker for lymphatic endothelial cells (LECs) and is pivotal in the process of lymphangiogenesis, a critical factor in cancer development and metastasis. Overexpression of LYVE-1 has been observed in various cancers, where it is recognized as an adverse prognostic indicator. Targeting LYVE-1 has demonstrated inhibitory effects on tumor cell proliferation, migration, and the formation of lymph node metastases both in vitro and in vivo. While extensive research has focused on the role of LYVE-1 in cancer cells, its involvement in virus infection and associated diseases remains largely unexplored. This review consolidates recent findings regarding the expression of LYVE-1 and its functions in lymphangiogenesis during various viral infections and the development of related diseases, with a particular emphasis on Kaposi's sarcoma herpesvirus. Despite the limited available data, it is evident that further studies are essential to comprehensively understand the contribution of LYVE-1 to viral pathogenesis and oncogenesis.

Development of human endogenous retrovirus type K- related treatments for human diseases.

Human endogenous retroviruses (HERVs) constitute approximately 8% of the human genome and have long been regarded as silent passengers within our genomes. However, the reactivation of HERVs has been increasingly linked to a range of human diseases, particularly the HERV-K (HML-2) family. Many studies are dedicated to elucidating the potential role of HERV-K in pathogenicity. While the underlying mechanisms require further investigation, targeting HERV-K transactivation emerges as a promising avenue for treating human diseases, including cancer, autoimmune disorders, neurodegenerative conditions, and infectious diseases. In this review, we summarize recent advancements in the development of HERV-K-targeted therapeutic strategies against various human diseases, including antiretroviral drugs, immunotherapy, and vaccines.

Coinfections with additional oncoviruses in HPV+ individuals: Status, function and potential clinical implications.

Oncovirus infections account for an estimated 12%-20% of human cancers worldwide. High-risk human papillomavirus (HPV) infection is the etiological agent of some malignancies such as cervical, oropharyngeal, anal, penile, vaginal, and vulvar cancers. However, HPV infection is not the only cause of these cancers or may not be sufficient to initiate cancer development. Actually, certain other risk factors including additional oncoviruses coinfections have been reported to increase the risk of patients exposed to HPV for developing different HPV-related cancers. In the current review, we summarize recent findings about coinfections with different oncoviruses in HPV+ patients from both clinical and mechanistic studies. We believe such efforts may lead to an interesting direction for improving our understanding and developing new treatments for virus-induced cancers.

Human endogenous retrovirus type K encoded Np9 oncoprotein induces DNA damage response.

Human endogenous retrovirus sequences (HERVs) constitute up to 8% of the human genome, yet not all HERVs remain silent passengers within our genomes. Some HERVs, especially the HERV type K (HERV-K), have been found to be frequently transactivated in a variety of inflammatory diseases and human cancers. Np9, a 9-kDa HERV-K encoded protein, has been reported as an oncoprotein and found present in a variety of tumors and transformed cells. In the current study, we for the first time reported that ectopic expression of Np9 protein was able to induce DNA damage response from host cells especially through upregulation of γH2AX. Furthermore, we found that direct knockdown of Np9 by RNAi in Kaposi's Sarcoma-associated herpesvirus (KSHV) infected cells effectively reduced LANA expression, the viral major latent oncoprotein in vitro and in vivo, which may represent a novel strategy against virus-associated malignancies.

Exploring gut-lung axis crosstalk in SARS-CoV-2 infection: Insights from a hACE2 mouse model.

Based on the forefront of clinical research, there is a growing recognition that the gut microbiota, which plays a pivotal role in shaping both the innate and adaptive immune systems, may significantly contribute to the pathogenesis of coronavirus disease 2019 (COVID-19). Although an association between altered gut microbiota and COVID-19 pathogenesis has been established, the causative mechanisms remain incompletely understood. Additionally, the validation of the precise functional alterations within the gut microbiota relevant to COVID-19 pathogenesis has been limited by a scarcity of suitable animal experimental models. In the present investigation, we employed a newly developed humanized ACE2 knock-in (hACE2-KI) mouse model, capable of recapitulating critical aspects of pulmonary and intestinal infection, to explore the modifications in the gut microbiota following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Examination of fecal samples using 16S rRNA gene profiling unveiled a notable reduction in species richness and conspicuous alterations in microbiota composition at 6 days postinfection (dpi). These alterations were primarily characterized by a decline in beneficial bacterial species and an escalation in certain opportunistic pathogens. Moreover, our analysis entailed a correlation study between the gut microbiota and plasma cytokine concentrations, revealing the potential involvement of the Lachnospiraceae_NK4A136_group and unclassified_f_Lachnospiraceae genera in attenuating hyperinflammatory responses triggered by the infection. Furthermore, integration of gut microbiota data with RNA-seq analysis results suggested that the increased presence of Staphylococcus in fecal samples may signify the potential for bacterial coinfection in lung tissues via gut translocation. In summary, our hACE2-KI mouse model effectively recapitulated the observed alterations in the gut microbiota during SARS-CoV-2 infection. This model presents a valuable tool for elucidating gut microbiota-targeted strategies aimed at mitigating COVID-19.

Association of dementia with impaired kidney function and plasma biomarkers: A population-based study.

BACKGROUND AND PURPOSE: Emerging evidence has linked impaired kidney function with dementia in older adults, but the neuropathological pathways underlying their association remain poorly understood. We sought to examine the relationships of kidney function with dementia and plasma biomarkers in a Chinese rural population. METHODS: This population-based study used data from the baseline examination of the Multimodal Interventions to Delay Dementia and Disability in rural China (MIND-China) cohort (March-September 2018; n = 5715). Kidney function was assessed using estimated glomerular filtration rate (eGFR) based on serum creatinine level. Dementia, Alzheimer's disease (AD) and vascular dementia (VaD) were diagnosed according to the international criteria. Plasma biomarkers were measured using the SIMOA platform in a subsample (n = 1446). Data were analyzed using logistic, general linear, and mediation models. RESULTS: Of the 5715 participants, 306 were diagnosed with dementia, including 195 with AD and 100 with VaD. Impaired kidney function (eGFR <60 vs. ≥90 mL/min/1.73 m2) was associated with multivariable-adjusted odds ratios of 2.24 (95% confidence interval [CI] 1.44-3.46) for all-cause dementia, 1.85 (1.07-3.18) for AD, and 2.49 (1.16-5.22) for VaD. In the biomarker subsample, impaired kidney function was significantly associated with higher plasma amyloid-ß (Aß)40 (ß-coefficient = 54.36, 95% CI 43.34-65.39), Aß42 (ß-coefficient = 3.14, 95% CI 2.42-3.86), neurofilament light chain (ß-coefficient = 10.62, 95% CI 5.62-15.62), and total tau (ß-coefficient = 0.68, 95% CI 0.44-0.91), and a lower Aß42/Aß40 ratio (ß-coefficient = -4.11, 95% CI -8.08 to -0.14). The mediation analysis showed that plasma total tau significantly mediated 21.76% of the association between impaired kidney function and AD (p < 0.05). CONCLUSION: Impaired kidney function is associated with dementia and plasma biomarkers among rural-dwelling older Chinese adults, and the association with AD is partly mediated by plasma biomarkers for neurodegeneration.

Anti-diabetic and anti-inflammatory indole diterpenes from the marine-derived fungus Penicillium sp. ZYX-Z-143.

Seven new indole-diterpenoids, penpaxilloids A-E (1-5), 7-methoxypaxilline-13-ene (6), and 10-hydroxy-paspaline (7), along with 20 known ones (8-27), were isolated from the marine-derived fungus Penicillium sp. ZYX-Z-143. Among them, compound 1 was a spiro indole-diterpenoid bearing a 2,3,3a,5-tetrahydro-1H-benzo[d]pyrrolo[2,1-b][1,3]oxazin-1-one motif. Compound 2 was characterized by a unique heptacyclic system featuring a rare 3,6,8-trioxabicyclo[3.2.1]octane unit. The structures of the new compounds were established by extensive spectroscopic analyses, NMR calculations coupled with the DP4 + analysis, and ECD calculations. The plausible biogenetic pathway of two unprecedented indole diterpenoids, penpaxilloids A and B (1 and 2), was postulated. Compound 1 acted as a noncompetitive inhibitor against protein tyrosine phosphatase 1B (PTP1B) with IC50 value of 8.60 ± 0.53 µM. Compound 17 showed significant α-glucosidase inhibitory activity with IC50 value of 19.96 ± 0.32 µM. Moreover, compounds 4, 8, and 22 potently suppressed nitric oxide production on lipopolysaccharide-stimulated RAW264.7 macrophages.

Nocturnal urination is associated with the presence of higher ventilatory chemosensitivity in patients with obstructive sleep apnea.

PURPOSE: Chemosensitivity is an essential part of the pathophysiological mechanisms of obstructive sleep apnea (OSA). This study aims to use the rebreathing method to assess hypercapnic ventilatory response (HCVR) and analyze the association between chemosensitivity and certain symptoms in patients with OSA. METHODS: A total of 104 male patients with diagnosed OSA were enrolled. The HCVR was assessed using rebreathing methods under hypoxia exposure to reflect the overall chemosensitivity. Univariate and multivariate linear regression were used to explore the association with chemosensitivity. Participants were enrolled in the cluster analysis using certain symptoms, basic characteristics, and polysomnographic indices. RESULTS: At similar baseline values, the high chemosensitivity group (n = 39) demonstrated more severe levels of OSA and nocturnal hypoxia than the low chemosensitivity group (n = 65). After screening the possible associated factors, nocturnal urination, rather than OSA severity, was found to be positively associated with the level of chemosensitivity. Cluster analysis revealed three distinct groups: Cluster 1 (n = 32, 34.0%) held younger, obese individuals with nocturnal urination, elevated chemosensitivity level, and very severe OSA; Cluster 2 (41, 43.6%) included middle-aged overweighted patients with nocturnal urination, increased chemosensitivity level, but moderate-severe OSA; and Cluster 3 (n = 21, 22.3%) contained middle-aged overweighted patients without nocturnal urination, with a lowered chemosensitivity level and only moderate OSA. CONCLUSION: The presence of nocturnal urination in male patients with OSA may be a sign of higher levels of ventilatory chemosensitivity, requiring early therapy efforts independent of AHI levels.

Influence of Rehabilitation Training-Based Procedural Follow-up on Pulmonary Function and Quality of Life in Patients Undergoing Coronary Angiography and Stenting.

Objective: This study aims to investigate the impact of procedural follow-up through rehabilitation training on enhancing postoperative pulmonary function and quality of life (QOL) in patients who have undergone coronary angiography and stenting. Methods: A total of 160 patients diagnosed with coronary heart disease (CHD) and having undergone percutaneous coronary intervention (PCI) between January 1, 2020, and December 31, 2021, were selected for the study. The random number method was employed to divide them into a control group and an experimental group. The control group (80 patients) received routine post-discharge follow-ups, while the experimental group (80 patients) underwent procedural follow-ups based on rehabilitation training. Pulmonary function and quality of life were assessed at discharge, 6 months post-discharge, and 12 months post-discharge using the Jaeger spirometer and the Assessment Scale of Quality of Life in Patients with CHD. Results: No statistically significant differences in pulmonary function and quality of life were observed between the two groups at the time of discharge (P > .05). However, 6 and 12 months post-discharge, the experimental group exhibited higher values for FEV1, FEV1%, FEV1/FVC, and VO2max compared to the control group. Additionally, total QOL scores, psychological function, and knowledge of CHD prevention and treatment were higher in the experimental group. However, there were no statistically significant differences in physical function and social adaptation ability. Conclusions: Procedural follow-ups based on rehabilitation training have the potential to improve postoperative cardiopulmonary function and quality of life in patients with coronary heart disease, thereby promoting recovery.

Impact of Narrative Nursing on Stigma and Psychological Crisis for Patients With Orthopedic Amputations.

Context: Amputation results in large wounds and in mobility disorders for patients, easily leading to social difficulties and affecting patients' psychological recovery. In recent years, some clinicians have used narrative nursing to intervene in the effects of stigma for patients with diseases other than amputations and have achieved good effects. Objective: The study intended to examine the impact of narrative nursing on amputation patients' feelings of stigma and on their resulting psychological crises. Design: The research team conducted a randomized controlled trial. Setting: The study occurred at the Affiliated Huaian No.1 People's Hospital of Nanjing Medical University in Huai'an, China. Participants: Participants were 75 patients who underwent lower-limb amputations at the hospital between November 2021 and May 2023. Interventions: The research team randomly divided participants into two groups: (1) the control group with 38 participants, who received conventional nursing, and (2) the intervention group, with 37 participants, who received a narrative nursing intervention in addition to conventional nursing. Outcome Measures: The research team measured: (1) stigma, using the Stigma Impact Scale (SIS); (2) anxiety and depression, using the Hospital Anxiety and Depression Scale (HADS); and (3) nursing satisfaction. The team also examined the correlation between participants' stigma scores and anxiety and depression scores. Results: Postintervention compared to the control group, the intervention group's: (1) SIS scores were significantly lower (P < .001); (2) anxiety and depression scores were significantly lower (both P < .001); (3) total nursing satisfaction rate was significantly higher (P = .011). The correlation analysis demonstrated a significant positive association between the SIS and the HADS scores (P < .05). Conclusions: Narrative nursing can improve the psychological states of amputees, mitigate their feelings of stigma, and elevate their nursing satisfaction, and it's worthy of clinical use.

Investigating the environmental capacity of soil heavy metals and its determinants in agro-pastoral regions of the qinghai-tibetan plateau.

Environmental capacity (EC) serves as the basis for environmental planning and management, as a key indicator for assessing environmental risk and quality, and as a foundation for achieving sustainable development. Studies on EC typically address agricultural or urban rather than pastoral areas, with few examining agro-pastoral areas. The EC of the Tibetan Plateau is particularly important, considering its importance as an agricultural area and ecological reserve. To address this gap, the Qingshizui area in Menyuan County, a typical agro-pastoral area on the Tibetan Plateau, was selected to quantify soil EC and its spatial distribution. In terms of the dynamic and static annual soil EC for this region, the heavy metals were ranked as follows, in ascending order: Cd, Hg, Co, As, Sb, Ni, Cu, Pb, Cr, and Zn. Most of the areas with high residual EC were in the west. For the 10 heavy metals, residual EC was significantly affected by geological background. For all the heavy metals except Zn and Hg, residual EC was significantly affected by soil type. The heavy metal elements in the agro-pastoral area's soil are mildly enriched, suggesting minimal human impact. The composite EC index of this soil is 0.98, indicating an intermediate EC and low health risk. This study underscores that integrating agriculture and pastoralism can optimize land use and mitigate ecological pressures associated with these practices when done separately. Our research provides valuable insights for resource optimization, environmental conservation, and enhancing the welfare of farmers and herders in the Qinghai-Tibet region.

Asymmetric Cu-N1O3 Sites Coupling Atop-type and Bridge-type Adsorbed *C1 for Electrocatalytic CO2-to-C2 Conversion.

2D functional porous frameworks offer a platform for studying the structure-activity relationships during electrocatalytic CO2 reduction reaction (CO2RR). Yet challenges still exist to breakthrough key limitations on site configuration (typical M-O4 or M-N4 units) and product selectivity (common CO2-to-CO conversion). Herein, a novel 2D metal-organic framework (MOF) with planar asymmetric N/O mixed coordinated Cu-N1O3 unit is constructed, labeled as BIT-119. When applied to CO2RR, BIT-119 could reach a CO2-to-C2 conversion with C2 partial current density ranging from 36.9 to 165.0 mA cm-2 in flow cell. Compared to the typical symmetric Cu-O4 units, asymmetric Cu-N1O3 units lead to the re-distribution of local electron structure, regulating the adsorption strength of several key adsorbates and the following catalytic selectivity. From experimental and theoretical analyses, Cu-N1O3 sites could simultaneously couple the atop-type (on Cu site) and bridge-type (on Cu-N site) adsorption of *C1 species to reach the CO2-to-C2 conversion. This work broadens the feasible C-C coupling mechanism on 2D functional porous frameworks.

Systematic Review of the Application of Computational Fluid Dynamics for Adult Aortic Diseases.

Background: Computational fluid dynamics (CFD) is a new medical method combining medicine and science. The aim of this study is to summarize and analyze the application of CFD in adult aortic diseases. Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search in the PubMed, Cochrane Library and Chinese databases identified 47 highly relevant articles. Studies were included if they assessed biomechanical markers and their potential association with progression or rupture of aortic aneurysms or dissections. Results: There are no randomized controlled trials to examine the direct relationship between all biomechanical parameters and aortic disease progression or rupture. Wall stress and peak wall rupture risk can predict the risk of aortic aneurysm rupture using biomechanics, which is more accurate than the prediction based on "diameter" alone. Areas with lower time averaged wall shear stress (TAWSS) and higher oscillatory shear index (OSI) are at risk for further aortic expansion or dissection. Higher relative residence time (RRT) area can predict platelet activation and thrombosis. In addition, pressure, flow field and other indicators can also roughly predict the risk of aortic disease progression. Conclusions: Contemporary evidence suggests that CFD can provide additional hemodynamic parameters, which have the potential to predict the progression of aortic lesions, the effect of surgical intervention, and prognosis.

Peroxiredoxin 1 of Procambarus clarkii govern immune responses during pathogen infection.

Members of the peroxiredoxin family are involved in a wide variety of physiological processes, including the ability to combat the effects of oxidative stress and immune responses, among others. Here, we cloned the cDNA of Procambarus clarkii Peroxiredoxin 1 (designated as PcPrx-1) and investigated its biological role in immune system functions in relation to microbial pathogens. The PcPrx-1 cDNA had 744 base pairs in an open reading frame that encoded 247 amino acid residues and contained a PRX_Typ2cys domain. The analysis of tissue specific expression patterns revealed that PcPrx-1 expression was ubiquitous in all tissues. In addition, the mRNA transcript of PcPrx-1 was found to be highest in the hepatopancreas. There was a significant upregulation of PcPrx-1 gene transcripts after exposure to LPS, PGN, and Poly I:C, but the transcription patterns were different after pathogen challenge. Double-stranded RNA was used to knockdown PcPrx-1, which resulted in a striking change in the expression of all the tested P. clarkii immune-associated genes, including lectin, Toll, cactus, chitinase, phospholipase, and sptzale. On the whole, these results suggest that PcPrx-1 is important to confer innate immunity against pathogens by governing the expression of critical transcripts that encode immune-associated genes.

Molecular cloning and functional characterization of peroxinectin from red swamp crayfish, Procambarus clarkii.

Peroxinectin, which has both peroxidase and cell adhesion activities, is crucial for invertebrate innate immune responses. In this study, we first cloned the full-length cDNA of Procambarus clarkii Peroxinectin (denoted as Pc-Px) and evaluated its immune roles. The Pc-Px cDNA had 2460 base pairs (bp) and 819 amino acid residues, including peroxidase domain and a putative integrin-binding motif. Pc-Px tissue expression was found to be ubiquitous in all examined tissues under normal physiological conditions. Pc-Px mRNA levels were highest in hemocytes, followed by gills and heart, and were lowest in the gut. The LPS, PGN, and Poly I:C treatment significantly up-regulated the transcript level of Pc-Px gene, but the expression trends were different after the microbials component treatments. Pc-Px knockdown using double-stranded RNA altered the transcription profiles of various immune-related genes in hepatopancreas of P. clarkii. Taken together, Pc-Px is an important component of immune system that likely to modulate immune function of P. clarkii via regulating immune-associated genes.