Performance evaluation of the MAGLUMI Hepatitis B virus surface antigen chemiluminescence immunoassay.

A highly sensitive and reliable Hepatitis B virus surface antigen (HBsAg) measurement is essential to universal screening, timely diagnosis, and management of Hepatitis B virus (HBV) infection. This study aimed to evaluate the performance of MAGLUMI HBsAg chemiluminescence immunoassay (CLIA). MAGLUMI HBsAg (CLIA) was compared against ARCHITECT HBsAg. 411 HBsAg positive samples, including different stages of infection, genotypes, subtypes, mutants, and 30 seroconversion panels were tested to evaluate diagnostic sensitivity. Diagnostic specificity was evaluated by testing 205 hospitalized samples and 5101 blood donor samples. Precision, limit of blank (LoB), limit of detection (LoD), and linearity were also verified. The diagnostic sensitivity of the MAGLUMI HBsAg (CLIA) was 100% with better seroconversion sensitivity than ARCHITECT HBsAg. The MAGLUMI HBsAg (CLIA) has optimal detection efficacy for HBV subgenotypes samples. The analytical sensitivity is 0.039 IU/mL. The initial diagnostic specificity is 99.63% on blood donors and 96.59% on hospitalized samples. The verification data demonstrated high repeatability, a LoB of 0.02 IU/mL, LoD of 0.05 IU/mL and an excellent linearity of 0.050-250 IU/mL (R2 = 0.9946). The MAGLUMI HBsAg (CLIA) is proved a highly sensitive and reliable assay with optimal subgenotype detection efficacy.

Effects of crown-to-implant ratio on marginal bone level and bone density in non-splinted single implants: a cross-sectional study.

BACKGROUND: Few studies have evaluated the effects of the crown-to-implant (C/I) ratio on the marginal bone level (MBL) and bone density in non-splinted single implants. The aim of this study was to assess the effect of C/I ratio on MBL and density of peri-implant bone in non-splinted posterior implants. METHODS: The C/I ratio, MBL, and grayscale values (GSVs) for bone density were measured from X-rays. Four areas of interest (two at the apical area and two at the middle of the peri-implant area) and two control areas were selected for evaluation. Follow-up radiographs were calibrated according to the control areas. RESULTS: In all, 117 non-splinted posterior implants in 73 patients followed up for a mean duration of 36.23 ± 10.40 (range 24-72) months were considered. The mean anatomical C/I ratio was 1.78 ± 0.43 (range 0.93 to 3.06). The mean change in MBL was 0.28 ± 0.97 mm. There were no significant associations between the C/I ratio and MBL changes (r = -0.028, p = 0.766). Pearson correlation showed a significant correlation between changes in GSV and the C/I ratio in the middle peri-implant area (r = 0.301, p = 0.001) and apical area (r = 0.247, p = 0.009). CONCLUSIONS: A higher C/I ratio of single non-splinted posterior implants is associated with increased peri-implant bone density, but not correlated with changes in MBL.

The Impacts of Polyisoprene Physical Interactions on Sorting of Single-Wall Carbon Nanotubes.

Conjugated polymer sorting is currently the best method to select large-diameter single-walled carbon nanotubes (SWCNTs) with tunable narrow chirality in the adaption of highly desired electronics applications. The acceleration on conjugated polymers-SWCNTs interaction with long-term stability through different molecular designs; for example, longer alkyl side-chains or conjugation moieties have been extensively developed in recent years. However, the importance of the macromolecules with abundant van der Waals (VDW) interaction in the conjugated-based block copolymer system acting during SWCNTs sorting is not clearly demonstrated. In this work, a conjugated diblock copolymer involving polyisoprene (PI) and highly dense π-interaction of poly (9,9-dioctylfluorene) (PFO) is utilized to investigate the impact of natural rubber PI physical interaction on sorting effectiveness and stability. Through the rational design of diblock copolymer, PFO with ≈1200 isoprene units can remarkably enhance SWCNTs sorting ability and selected few chiralities with a diameter of ≈0.83-1.1 nm and highly stable solution for more than 1 year. The introduction of long-chain PI system is attributed not only to form weak VDW force with SWCNTs and strengthen the wrapping of PFO around the semiconducting SWCNTs but also to act as a barrier among nanotubes to prevent reaggregation of sorted SWCNTs.

End-to-End Deep Learning by MCU Implementation: An Intelligent Gripper for Shape Identification.

This paper introduces a real-time processing and classification of raw sensor data using a convolutional neural network (CNN). The established system is a microcontroller-unit (MCU) implementation of an intelligent gripper for shape identification of grasped objects. The pneumatic gripper has two embedded accelerometers to sense acceleration (in the form of vibration signals) on the jaws for identification. The raw data is firstly transferred into images by short-time Fourier transform (STFT), and then the CNN algorithm is adopted to extract features for classifying objects. In addition, the hyperparameters of the CNN are optimized to ensure hardware implementation. Finally, the proposed artificial intelligent model is implemented on a MCU (Renesas RX65N) from raw data to classification. Experimental results and discussions are introduced to show the performance and effectiveness of our proposed approach.

EZH2 inhibitors reverse resistance to gefitinib in primary EGFR wild-type lung cancer cells.

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. In traditional anti-cancer therapy, epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI) have been proven to be beneficial for patients with EGFR mutations. However, patients with EGFR wild-type NSCLC were usually not respond to EGFR-TKIs. Enhancer of zeste homolog 2 (EZH2) is a key molecular in the PRC2 complex and plays an important role in epigenetic regulation and is overexpressed in variant tumors. EZH2 inhibitors have been reported to sensitize variant tumor cells to anticancer drugs. This study aimed to investigate whether the EZH2 inhibitors, GSK343 and DZNep when combined with gefitinib can reverse EGFR-TKIs resistance in EGFR wild-type NSCLC cells. METHODS: The RNA-sequencing data of patients with NSCLC [502 patients with lung squamous cell carcinoma, including 49 paracancerous lung tissues and 513 patients with lung adenocarcinoma (LUAD), including 59 paracancerous lung tissues] from the Cancer Genome Atlas (TCGA), were analyzed for EZH2 expression. EZH2 expression was verified in 40 NSCLC tissue cancer samples and their corresponding paracancerous tissues from our institute (TJMUGH) via RT-PCR. A549 and H1299 cells treated with siRNA or EZH2 inhibitors were subjected to cell viability and apoptosis analyses as well to EGFR pathway proteins expression analyses via western blotting. RESULTS: EZH2 was upregulated in human NSCLC tissues and correlated with poor prognosis in patients with LUAD based on data from both TCGA and TJMUGH. Both GSK343 and DZNep sensitized EGFR wild-type LUAD cells (A549 and H1299) to gefitinib and suppressed cell viability and proliferation in vitro by downregulating the phosphorylation of EGFR and AKT and by inducing cell apoptosis. Co-administration of EZH2 inhibitors (GSK343 or DZNep) with gefitinib exerted a stronger inhibitory effect on tumor activity, cell proliferation and cell migration than single drug administration in vitro and in vivo. CONCLUSIONS: These data suggest that the combination of EZH2 inhibitors with EGFR-TKIs may be an effective method for treating NSCLC-patients with EGFR-wild type, who do not want to undergo traditional treatment with chemotherapy.

Antibody development and property analysis of RhBST2 for accurate cell biological and viral research.

BST2 is a single-pass type II transmembrane (TM) protein, which has a cytoplasmic domain, a transmembrane domain, and an extracellular domain, each domain is important for biologic function of BST2. BST2 is a host restriction factor that can effectively inhibit retrovirus release. Rhesus monkeys are considered as relevant natural animal models for studying AIDS in humans. In order to recognize rhesus BST2 (RhBST2) protein and detect its function accurately, we prepared a polyclonal antibody (pAb) especially for RhBST2. Meanwhile, we constructed RhBST2 proteins with the addition of an HA-tag at the N-terminus (RhBST2-NHA) or inside of the ectodomain (RhBST2-IHA) to compare the recognition ability of rabbit anti-RhBST2 pAb and anti-HA mAb. The results showed that the anti-HA mAb and rabbit anti-RhBST2 pAb had the same ability to identify RhBST2. RhBST2 demonstrated antiviral activity and the ability to activate NF-κB. Moreover, the N-glycosylation states, cell surface level and intracellular localization of RhBST2 were detected. However, HA tags relatively changed part of the biological function of RhBST2. These results show that the RhBST2 polyclonal antibody is more suitable for analyzing the properties and functions of RhBST2, and the natural domain of RhBST2 is very important for its function.

The effect of leech extracts on endothelial cell coagulation-related factors and endothelial dysfuction-related molecules.

OBJECTIVE: This study was focused on screening leech extracts to identify those with little or no anti-coagulation effect or with significant anti-endothelial dysfunction activity. METHODS: Different leech extracts were prepared by enzymolysis and microbial transformation and their cytotoxicity were measured by MTT assay. The effect of different leech extracts on mRNA expression of coagulation-related factors (PAI, vWF, tPA, PS, TFPI, TM) was quantified by RT-PCR. After identifying a leech extract with little anti-coagulatory effect, RT-PCR was then used to assess the effect of this extract on the mRNA expression of endothelial dysfunction-related molecules (ET-1, iNOS, MCP-1, IL-6). RESULTS: 8 leech extracts were obtained, including 4 enzymatic extracts (LP, PHL, PTHL, CEHL) and 4 Lactobacillus metabolites (MRS, MRS-1, MRS-2, and MRS-3). Following optimization of conditions using MTT assays, we treated EA.hy926 cells with 0, 12.5, 25, 50 µg/mL of LP, PTHL, CEHL, MRS, MRS-1 or MRS-3 extract for 24 h. We found that PHL and MRS-1 had no significant effect on coagulation-related factors. Furthermore, treatment with 50 µg/mL PHL resulted in significant decreases in ET-1, iNOS, MCP-1, and IL-6 mRNA expression by 28.06%, 33.30%, 19.80%, and 52.34%, respectively. CONCLUSIONS: In the present study, we found that PHL, a pepsin hydrolysate of leech with little anti-coagulatory effect, could significantly suppress TNF-α induced mRNA overexpression of endothelial dysfunction-related molecules (ET-1, iNOS, MCP-1, and IL-6). These results provide a reliable experimental basis for identifying new anti-atherosclerosis therapeutics for long term use and with minimal bleeding side effects.

HOTAIR lncRNA SNPs rs920778 and rs1899663 are associated with smoking, male gender, and squamous cell carcinoma in a Chinese lung cancer population.

The abnormal expression of the long noncoding RNA (lncRNA) HOX transcript intergenic antisense RNA (HOTAIR) plays an important role in the development of various cancers; however, single nucleotide polymorphisms (SNPs) in HOTAIR and their association with primary lung cancer susceptibility have not yet been reported. Here, we performed a case-control study including 262 primary lung cancer patients and 451 cancer-free control individuals to investigate the association between four haplotype-tagging SNPs (rs920778, rs12826786, rs4759314, and rs1899663) in the HOTAIR lncRNA and the risk of developing primary lung cancer. We found a significant association between the SNPs rs920778 and rs1899663 in the HOTAIR and primary lung cancer susceptibility (P < 0.05). Moreover, homozygous C/T (C/T + TT) for rs920778 (C > T) sites was significantly associated with gender, smoking history, and pathological type. In addition, linkage disequilibrium and haplotype analysis of HOTAIR gene polymorphisms for susceptibility to lung cancer revealed a high degree of linkage disequilibrium between the rs920778 and rs1899663 loci (D' = 0.86, r2 = 0.52). The population of rs920778, rs1899663, and rs4759314 had a significantly increased risk of lung cancer (P < 0.001). In summary, the present study provides persuasive evidence that SNP rs920778 is closely correlated with susceptibility to primary lung cancer. Future studies are warranted to validate and expand these findings, and to further dissect the importance of these SNPs in the development of primary lung cancer.

Lrp, a global regulator, regulates the virulence of Vibrio vulnificus.

BACKGROUND: An attenuated mutant (designated NY303) of Vibrio vulnificus, which causes serious wound infection and septicemia in humans, was isolated fortuitously from a clinical strain YJ016. This mutant was defective in cytotoxicity, migration on soft agar and virulence in the mouse. The purpose of this study was to map the mutation in this attenuated mutant and further explore how the gene thus identified is involved in virulence. METHODS: The whole genome sequence of mutant NY303 determined by next-generation sequencing was compared with that of strain YJ016 to map the mutations. By isolating and characterizing the specific gene-knockout mutants, the gene associated with the phenotype of mutant NY303 was identified. This gene encodes a global regulator, Lrp. A mutant, YH01, deficient in Lrp was isolated and examined in vitro, in vivo and ex vivo to find the affected virulence mechanisms. The target genes of Lrp were further identified by comparing the transcriptomes, which were determined by RNA-seq, of strain YJ016 and mutant YH01. The promoters bound by Lrp were identified by genome footprinting-sequencing, and those related with virulence were further examined by electrophoretic mobility shift assay. RESULTS: A mutation in lrp was shown to be associated with the reduced cytotoxicity, chemotaxis and virulence of mutant NY303. Mutant YH01 exhibited a phenotype resembling that of mutant NY303, and was defective in colonization in the mouse and growth in mouse serum, but not the antiphagocytosis ability. 596 and 95 genes were down- and up-regulated, respectively, in mutant YH01. Many of the genes involved in secretion of the MARTX cytotoxin, chemotaxis and iron-acquisition were down-regulated in mutant YH01. The lrp gene, which was shown to be negatively autoregulated, and 7 down-regulated virulence-associated genes were bound by Lrp in their promoters. A 14-bp consensus sequence, mkCrTTkwAyTsTG, putatively recognized by Lrp was identified in the promoters of these genes. CONCLUSIONS: Lrp is a global regulator involved in regulation of cytotoxicity, chemotaxis and iron-acquisition in V. vulnificus. Down-regulation of many of the genes associated with these properties may be responsible, at least partly, for loss of virulence in mutant NY303.

Evaluation of the microscopic observation drug susceptibility assay for the rapid detection of MDR-TB and XDR-TB in China: a prospective multicentre study.

OBJECTIVES: To perform a multicentre study evaluating the performance of the microscopic observation drug susceptibility (MODS) assay for the detection of MDR-TB and XDR-TB in high-burden resource-limited settings. METHODS: We performed a prospective diagnostic accuracy study of drug-resistant TB suspects from outpatient and inpatient settings in five laboratories in China. Sputum was tested by smear microscopy, liquid [mycobacterial growth indicator tube (MGIT)] culture and the MODS assay at each site. Drug susceptibility testing (DST) was by MODS and an indirect 1% proportion method. The reference standard for Mycobacterium tuberculosis detection was growth on MGIT culture; the 1% proportion method was the reference standard for rifampicin, isoniazid, ofloxacin, kanamycin and capreomycin DST. RESULTS: M. tuberculosis was identified by reference standard culture among 213/532 (40.0%) drug-resistant TB suspects. Overall MODS sensitivity for M. tuberculosis detection was 87.8%-94.3% and specificity was 96.8%-100%. For drug-resistant TB diagnosis, excellent agreement was obtained for all drugs tested at the majority of sites. The accuracy was 87.1%-96.7% for rifampicin, 87.1%-93.3% for isoniazid, 92.7%-100% for ofloxacin, 90.9%-100% for kanamycin and 90.2%-100% for capreomycin. The median time to culture positivity was significantly shorter for MODS than for the MGIT liquid culture (8 days versus 11 days, P<0.001). The contamination rate ranged between 2.1% and 5.3%. CONCLUSIONS: In the study settings, MODS provided high sensitivity and specificity for rapid diagnosis of TB and drug-resistant TB. We consider it to have a strong potential for timely detection of MDR-TB and XDR-TB in high-burden resource-limited settings.

Rapid diagnosis of pleural tuberculosis by Xpert MTB/RIF assay using pleural biopsy and pleural fluid specimens.

BACKGROUND: Early pleural tuberculosis (TB) diagnosis is particularly difficult. The aim of this study was to investigate the diagnostic accuracy of the Xpert MTB/RIF (Xpert) (Cepheid, Sunnyvale, CA) assay using pleural biopsy and pleural fluid specimens in patients with suspected pleural TB but who had a negative sputum acid-fast bacilli (AFB) smear. MATERIALS AND METHODS: In this study, 134 sputum smear-negative suspected pleural TB patients were selected. Paired pleural fluid and pleural biopsy specimens were tested for Mycobacterium tuberculosis by standard smear-microscopy, Lowenstein-Jensen and mycobacterial growth indicator tube (MGIT) culture, and the Xpert assay. Mycobacterial culture from pleural biopsy specimens was used as a reference standard for sensitivity and specificity calculations. Detection of rifampicin resistance was compared with the MGIT method. RESULTS: Of 126 evaluable patients, 55 received a diagnosis of pleural TB. The sensitivity of the Xpert assay using pleural biopsy specimens for the diagnosis of pleural TB was 85.5%, and specificity was 97.2%. The sensitivity and specificity of the Xpert assay in pleural fluid were 43.6% and 98.6%, respectively. The Xpert assay correctly identified 90.0% of phenotypic rifampicin-resistant cases and 93.9% of phenotypic rifampicin-susceptible cases. CONCLUSION: The Xpert assay on pleural biopsy specimens may provide an accurate diagnosis of pleural TB in patients who had a negative AFB smear.

Unveiling IL6R and MYC as Targeting Biomarkers in Imatinib-Resistant Chronic Myeloid Leukemia through Advanced Non-Invasive Apoptosis Detection Sensor Version 2 Detection.

The management of chronic myelogenous leukemia (CML) has seen significant progress with the introduction of tyrosine kinase inhibitors (TKIs), particularly Imatinib. However, a notable proportion of CML patients develop resistance to Imatinib, often due to the persistence of leukemia stem cells and resistance mechanisms independent of BCR::ABL1 This study investigates the roles of IL6R, IL7R, and MYC in Imatinib resistance by employing CRISPR/Cas9 for gene editing and the Non-Invasive Apoptosis Detection Sensor version 2 (NIADS v2) for apoptosis assessment. The results indicate that Imatinib-resistant K562 cells (K562-IR) predominantly express IL6R, IL7R, and MYC, with IL6R and MYC playing crucial roles in cell survival and sensitivity to Imatinib. Conversely, IL7R does not significantly impact cytotoxicity, either alone or in combination with Imatinib. Further genetic editing experiments confirm the protective functions of IL6R and MYC in K562-IR cells, suggesting their potential as therapeutic targets for overcoming Imatinib resistance in CML. This study contributes to understanding the mechanisms of Imatinib resistance in CML, proposing IL6R and MYC as pivotal targets for therapeutic strategies. Moreover, the utilization of NIADS v2 enhances our capability to analyze apoptosis and drug responses, contributing to a deeper understanding of CML pathogenesis and treatment options.

Programmed Death Ligand-1-Overexpressing Donor Exosomes Mediate Donor-Specific Immunosuppression by Delivering Co-Inhibitory Signals to Donor-Specific T Cells.

Programmed death ligand-1 (PD-L1) and donor antigens are critical for donor immature dendritic cells (DCs) targeting donor-specific T cells to induce transplant tolerance. This study aims to clarify whether DC-derived exosomes (DEX) with donor antigens (H2b) and high levels of PD-L1 expression (DEXPDL1+ ) can help to suppress graft rejection. In this study, it is demonstrated that DEXPDL1+ presents donor antigens, as well as PD-L1 co-inhibitory signals, directly or semi-directly via DCs to H2b-reactive T cells. This dual signal presentation can prolong the survival of heart grafts from B6 (H2b) mice but not from C3H (H2k) mice by inhibiting T cell activation, inducing activated T cell apoptosis, and modulating the balance of T cell differentiation from inflammatory to regulatory. Additionally, even though DEXPDL1+ treatment cannot induce tolerance after short-term treatment, this study provides a new vehicle for presenting co-inhibitory signals to donor-specific T cells. This novel strategy may facilitate the realization of donor-specific tolerance via the further optimization of drug-loading combinations and therapeutic regimens to elevate their killing ability.

The Presence of EGFR T790M in TKI-Naïve Lung Cancer Samples of Patients Who Developed a T790M-Positive Relapse on First or Second Generation TKI Is Rare.

EGFR-mutated non-small cell lung cancer (NSCLC) patients can be effectively treated with tyrosine kinase inhibitors (TKI) but frequently present with an EGFR T790M resistance mutation at relapse. We aimed to screen for T790M in pre-treatment formalin-fixed and paraffin-embedded (FFPE) tissue samples of patients with a confirmed T790M mutation at progression. We analyzed 33 pre-treatment DNA samples of NSCLC patients who progressed upon TKI between 2013 to 2019. To establish storage-time dependent formalin fixation-induced background levels for C>T mutations, we analyzed DNA isolated from archival (stored >1 year, n = 22) and recently generated (stored <1 month, n = 11) FFPE samples and included DNA isolated from white blood cells (WBC) (n = 24) as controls. DNA samples were analyzed by droplet digital (dd)PCR, and positivity was defined by outlier detection according to Grubb's criterion. The T790M background allele frequency levels were 0.160% in DNA isolated from archival-FFPE, 0.100% in fresh FFPE, and 0.035% in WBC. Progression-free survival (PFS) time of the single T790M positive patient was 9 months, while T790M negative patients had a median PFS of 10 months (range 2−27). Proper storage time matched FFPE control samples are essential for reliable detection of T790M mutation at low VAF. The presence of EGFR T790M mutations in pre-TKI samples is rare, even in patients who progressed with EGFR T790M mutations.

Clinical and Microbiological Characteristics of Culture-Positive, Influenza-Associated Pulmonary Aspergillosis: A Single-Center Study in Southern Taiwan, 2016-2019.

This study delineated the characteristics of 24 (11.2%) culture-positive, influenza-associated pulmonary aspergillosis (IAPA) patients out of 215 patients with severe influenza during 2016-2019 in a medical center in southern Taiwan. Twenty (83.3%) patients did not have EORTC/MSG-defined host factors. The mean time from influenza diagnosis to Aspergillus growth was 4.4 days, and 20 (83.3%) developed IAPA within seven days after influenza diagnosis. All patients were treated in intensive care units and all but one (95.8%) received mechanical ventilation. Aspergillus tracheobronchitis was evident in 6 (31.6%) of 19 patients undergoing bronchoscopy. Positive galactomannan testing of either serum or bronchoalveolar lavage was noted in all patients. On computed tomography imaging, IAPA was characterized by peribronchial infiltrates, multiple nodules, and cavities superimposed on ground-glass opacities. Pure Aspergillus growth without bacterial co-isolation in culture was found in 17 (70.8%) patients. A. fumigatus (15, 62.5%), A. flavus (6, 25.0%), and A. terreus (4, 16.7%) were the major causative species. Three patients had mixed Aspergillus infections due to two species, and two had mixed azole-susceptible and azole-resistant A. fumigatus infection. All patients received voriconazole with an all-cause mortality of 41.6%. Of 14 survivors, the mean duration of antifungal use was 40.5 days. In conclusion, IAPA is an early and rapidly deteriorating complication following influenza that necessitates clinical vigilance and prompt diagnostic workup.

HOTAIR promotes gefitinib resistance through modification of EZH2 and silencing p16 and p21 in non-small cell lung cancer.

The long non-coding RNA Hox transcript antisense intergenic RNA (HOTAIR) plays a critical role in tumorigenesis as well as drug resistance in various cancers. However, the molecular mechanism by which HOTAIR induces gefitinib resistance in non-small cell lung cancer is to date unclear. In the present study, we revealed that HOTAIR is upregulated in gefitinib-resistant lung cancer cells and over-expression of HOTAIR enhances gefitinib resistance in lung cancer cells. In addition, the overexpression of HOTAIR promotes cell cycle progression through epigenetic regulation of EZH2/H3K27. Silencing of EZH2 by either siRNA or inhibitors sensitized the lung cancer cells to gefitinib. Inhibition of EZH2 induces expression of p16 and p21, whereas levels of CDK4, cyclinD1, E2F1, and LSD1 are significantly decreased in PC-9 cells overexpressing HOTAIR. ChIP-PCR experiments indicate that HOTAIR increases H3K27me3 recruitment to the promoter of p16 and p21 in PC-9 lung cancer cells overexpressing HOTAIR. In xenograft mouse models, overexpressing HOTAIR in lung cancer tissues decreased p16 and p21 proteins. Taken together, these data suggest that HOTAIR contributes to gefitinib resistance by regulating EZH2 and p16 and p21. Targeting HOTAIR may be a novel therapeutic strategy for treating gefitinib-resistance in non-small cell lung cancer.

Antiviral Activity of Feline BCA2 Is Mainly Dependent on Its Interference With Proviral Transcription Rather Than Degradation of FIV Gag.

Human BCA2/RNF115/Rabring7 (hBCA2) is a RING type E3 ubiquitin ligase with the ability of autoubiquitination or promoting protein ubiquitination. It also acts as a host restriction factor has BST2-dependent and BST2-independent antiviral activity to inhibit the release of HIV-1. In a previous study, we demonstrated that feline BCA2 (fBCA2) also has E3 ubiquitin ligase activity, although its antiviral mechanism remained unclear. In this study, we showed that fBCA2 can interact with feline BST2 (fBST2) and exhibits an fBST2-independent antiviral function, and the RING domain is necessary for the antiviral activity of fBCA2. fBCA2 could degrade HIV-1 Gag and restrict HIV-1 transcription to counteract HIV-1 but not promote the degradation of HIV-1 through lysosomal. Furthermore, for both fBCA2 and hBCA2, restricting viral transcription is the main anti-FIV mechanism compared to degradation of FIV Gag or promoting viral degradation. Consequently, transcriptional regulation of HIV or FIV by BCA2 should be the primary restriction mechanism, even though the degradation mechanism is different when BCA2 counteracts HIV or FIV. This may be due to BCA2 has a special preference in antiviral mechanism in the transmission of primate or non-primate retroviruses.

Usefulness of real-time three-dimensional echocardiography for diagnosis of infective endocarditis.

OBJECTIVES: To compare transthoracic 2-dimentional echocardiography (2DE) and real-time three-dimensional echocardiography (RT-3DE) evaluation of clinically suspected infective endocarditis (IE) and to determine the feasibility of RT-3DE in vegetation detection. DESIGNS: There were 46 patients (mean age 61+/-17 years, 54% male) enrolled. We acquired 2DE and RT-3DE with full volume images. RT-3DE images were analyzed by 3D QLAB software. Parameters suggestive of vegetation for RT-3DE assessment included mobile nodules, focal thickness, and uneven surface. The diagnosis of IE was made according to the Duke criteria. RESULTS: The sensitivity and specificity were 91.6% and 88.2% for 2DE, and 91.6% and 100% for RT-3DE. Among three parameters of RT-3DE, presence of mobile nodule (83.3% vs. 0%, p < 0.001) were significantly higher in IE patients but not focal thickness (75% vs. 65%, p = 0.723), or uneven surface (33% vs. 10%, p = 0.064). CONCLUSION: The sensitivity of RT-3DE and 2DE was similar for endocarditis diagnosis, but the specificity of RT-3DE was higher. Mobile nodules viewed by RT-3DE might be a useful finding for vegetation detection.

Uric acid is an independent predictor of arterial stiffness in hypertensive patients.

Increased arterial stiffness is an important marker for target organ damage in essential hypertension. Both serum uric acid (UA) and C-reactive protein (CRP) were reported to be associated with target organ damage. However, the influences of UA and CRP on large arterial stiffness were not well elucidated. This study included 200 essential hypertension patients (64 women) whose age was between 20 and 50 years old (mean age 41 +/- 8 years). None of the patients had diabetes mellitus or overt end-organ damage. Arterial stiffness was assessed by pulse-wave velocity (PWV) measured by tonometry from carotid to radial artery. Serum UA, high-sensitivity CRP (hsCRP), glucose, insulin, and lipid profiles were measured at the same time in each patient. PWV levels were significantly correlated with mean blood pressure (r = 0.245, P < 0.001), diastolic blood pressure (r = 0.323, P < 0.001), high-density lipoprotein (r = -0.169, P = 0.016), and UA (r = 0.234, P = 0.001), but not age, body mass index, blood sugar, insulin, low-density lipoprotein, triglyceride, and hsCRP. Pulse-wave velocity levels were significantly higher in males (8.9 +/- 1.2 vs 8.2 +/- 1.2 m/s, P < 0.001) and smokers (9.3 +/- 1.1 vs 8.5 +/- 1.2 m/s, P < 0.001). Uric acid was significantly correlated with hsCRP (r = 0.294, P < 0.001). After multivariate analysis controlling for all possible confounding factors, UA (odds ratio 1.28, 95% confidence interval 1.02-1.61, P = 0.032) was still independently associated with increased PWV. In conclusion, UA but not hsCRP was independently associated with increased PWV in essential hypertension. Although UA was correlated with hsCRP, the association between UA and PWV was not through the effect of enhanced inflammation.

Association of left atrial strain and strain rate assessed by speckle tracking echocardiography with paroxysmal atrial fibrillation.

BACKGROUND: We hypothesized that contraction of the LA wall could be documented by speckle tracking and could be applied for assessment of LA function. This study tried to identify the association between LA longitudinal strain (LAS) and strain rate (LASR) measured by speckle tracking with paroxysmal atrial fibrillation (PAF). METHODS: Fifty-two patients (61 +/- 17 years old, 23 men) with sinus rhythm at baseline referred for the evaluation of episodic palpitation were included. Standard four-chamber and two-chamber views were acquired and analyzed off-line. Peak LAS and LASR were carefully identified as the peak negative inflection of speckle tracking waves after P-wave gated by electrocardiography. RESULTS: Ten patients (19%) had PAF. LAS, LASR, age, left ventricular end-diastolic dimension, left ventricular mass, LA volume, and mitral early filling-to-annulus early velocity ratio were different between patients with and without PAF. After multivariate analysis, LASR was significantly independently associated with PAF (OR 8.56, 95% CI 1.14-64.02, P = 0.036). CONCLUSION: Speckle tracking echocardiography could be used in measurements of LAS and LASR. Decreased negative LASR was independently associated with PAF.