Porcine deltacoronavirus nsp5 antagonizes type I interferon signaling by cleaving IFIT3.

Porcine deltacoronavirus (PDCoV) has caused enormous economic losses to the global pig industry. However, the immune escape mechanism of PDCoV remains to be fully clarified. Transcriptomic analysis revealed a high abundance of interferon (IFN)-induced protein with tetratricopeptide repeats 3 (IFIT3) transcripts after PDCoV infection, which initially implied a correlation between IFIT3 and PDCoV. Further studies showed that PDCoV nsp5 could antagonize the host type I interferon signaling pathway by cleaving IFIT3. We demonstrated that PDCoV nsp5 cleaved porcine IFIT3 (pIFIT3) at Gln-406. Similar cleavage of endogenous IFIT3 has also been observed in PDCoV-infected cells. The pIFIT3-Q406A mutant was resistant to nsp5-mediated cleavage and exhibited a greater ability to inhibit PDCoV infection than wild-type pIFIT3. Furthermore, we found that cleavage of IFIT3 is a common characteristic of nsp5 proteins of human coronaviruses, albeit not alphacoronavirus. This finding suggests that the cleavage of IFIT3 is an important mechanism by which PDCoV nsp5 antagonizes IFN signaling. Our study provides new insights into the mechanisms by which PDCoV antagonizes the host innate immune response.IMPORTANCEPorcine deltacoronavirus (PDCoV) is a potential emerging zoonotic pathogen, and studies on the prevalence and pathogenesis of PDCoV are ongoing. The main protease (nsp5) of PDCoV provides an excellent target for antivirals due to its essential and conserved function in the viral replication cycle. Previous studies have revealed that nsp5 of PDCoV antagonizes type I interferon (IFN) production by targeting the interferon-stimulated genes. Here, we provide the first demonstration that nsp5 of PDCoV antagonizes IFN signaling by cleaving IFIT3, which affects the IFN response after PDCoV infection. Our findings reveal that PDCoV nsp5 is an important interferon antagonist and enhance the understanding of immune evasion by deltacoronaviruses.

Trends and insights in dengue virus research globally: a bibliometric analysis (1995-2023).

BACKGROUND: Dengue virus (DENV) is the most widespread arbovirus. The World Health Organization (WHO) declared dengue one of the top 10 global health threats in 2019. However, it has been underrepresented in bibliometric analyses. This study employs bibliometric analysis to identify research hotspots and trends, offering a comprehensive overview of the current research dynamics in this field. RESULTS: We present a report spanning from 1995 to 2023 that provides a unique longitudinal analysis of Dengue virus (DENV) research, revealing significant trends and shifts not extensively covered in previous literature. A total of 10,767 DENV-related documents were considered, with a notable increase in publications, peaking at 747 articles in 2021. Plos Neglected Tropical Diseases has become the leading journal in Dengue virus research, publishing 791 articles in this field-the highest number recorded. Our bibliometric analysis provides a comprehensive mapping of DENV research across multiple dimensions, including vector ecology, virology, and emerging therapies. The study delineates a complex network of immune response genes, including IFNA1, DDX58, IFNB1, STAT1, IRF3, and NFKB1, highlighting significant trends and emerging themes, particularly the impacts of climate change and new outbreaks on disease transmission. Our findings detail the progress and current status of key vaccine candidates, including the licensed Dengvaxia, newer vaccines such as Qdenga and TV003, and updated clinical trials. The study underscores significant advancements in antiviral therapies and vector control strategies for dengue, highlighting innovative drug candidates such as AT-752 and JNJ-1802, and the potential of drug repurposing with agents like Ribavirin, Remdesivir, and Lopinavir. Additionally, it discusses biological control methods, including the introduction of Wolbachia-infected mosquitoes and gene-editing technologies. CONCLUSION: This bibliometric study underscores the critical role of interdisciplinary collaboration in advancing DENV research, identifying key trends and areas needing further exploration, including host-virus dynamics, the development and application of antiviral drugs and vaccines, and the use of artificial intelligence. It advocates for strengthened partnerships across various disciplines to effectively tackle the challenges posed by DENV.

Epidemiological and evolutionary analysis of canine circovirus from 1996 to 2023.

BACKGROUND: Canine circovirus (CanineCV), a non-enveloped virus with a circular DNA genome, has been identified in various avian and mammalian species, including domestic and wild canids. This study aimed to comprehensively analyze the prevalence of CanineCV across diverse animal species in 11 provinces of China. RESULTS: A total of 1,666 serum samples were collected, revealing a 5.82% prevalence of CanineCV in dogs, with the highest rates being observed in southern and eastern China. Phylogenetic analysis of 266 global CanineCV genomes sourced from the NCBI identified six distinct genotypes, elucidating the complex dynamics of their evolution. Evidence suggested a potential bat origin for CanineCV, with positive selection and high rates of evolution being observed. Recombination analysis revealed dynamic genetic exchange, highlighting the intricate nature of CanineCV evolution. Mutational analysis identified key amino acid substitutions likely to influence the virus's adaptation. Additionally, glycosylation, palmitoylation, and SUMOylation sites were predicted, shedding light on crucial functional properties of the virus. CONCLUSIONS: This study provides a global perspective on the origin, genetic diversity, and evolutionary dynamics of CanineCV. Understanding these factors is crucial for elucidating its epidemiology and potential health risks.

The Hanks-like serine/threonine protein kinase YihE is crucial for Aeromonas veronii virulence and adhesion.

Aeromonas veronii is an important pathogen found in various aquatic environments and products, posing a threat to public health. The Hanks-like serine/threonine protein kinase is closely linked to the pathogenesis of pathogenic bacteria, but the exact role of YihE in A. veronii remains still unknown. To study the specific function of the YihE kinase, we constructed a knockout mutant of the yihE gene in A. veronii. The deletion of the yihE gene resulted in changes to the metabolism of L-arginine-AMC and acetic acid, as well as enhanced resistance to ampicillin and kanamycin in A. veronii. Additionally, the ΔyihE strain demonstrated a 1.4-fold increase in biofilm formation ability and a 1.8-fold decrease in adhesion and invasion to EPCs when compared to the wild-type strain. A significant decrease in cytotoxicity was observed at 2 and 3 h post-infection with EPCs compared to the wild-type strain. Additionally, the deletion of the yihE gene was associated with a significant decrease in motility of the strain. Furthermore, the deletion of the yihE gene resulted in a 1.44-fold increase in the LD50 of A. veronii in zebrafish. These findings offer valuable insights into the pathogenic mechanisms of A. veronii.

Application and Research Progress of Ultrasound-Guided Brachial Plexus Block Through Costoclavicular Space Approach in Upper Limb Surgery.

Objective: Exploring newer approaches to brachial plexus block is crucial for improving surgical outcomes and patient comfort. This study aims to review the application and research progress of ultrasound-guided brachial plexus block via the costoclavicular space approach in upper limb surgery. Methods: This study provides a comprehensive review of existing literature, studies, and clinical cases related to the costoclavicular approach. The advantages and disadvantages of conventional approaches for brachial plexus block, including the intermuscular groove method, supraclavicular method, and axillary approach, are discussed. The anatomical characteristics of the costoclavicular space are examined, and the methods of brachial plexus nerve block using ultrasound-guided costoclavicular space approach are described. It holds great promise for enhancing patient care and increasing the overall success rate of surgical procedures. Results: The costoclavicular space approach for brachial plexus block offers several advantages, including stable anatomical structure, low nerve variation rate, and clear visualization of each nerve bundle under ultrasound imaging. Compared to traditional approaches, ultrasound-guided brachial plexus block via the costoclavicular space approach has a high success rate, rapid onset of anesthesia, and high safety. Conclusion: Ultrasound-guided brachial plexus block via the costoclavicular space approach is effective and safe in upper limb surgery. It provides good anesthesia and postoperative analgesia, making it a valuable technique for various upper limb surgeries. The potential clinical significance of our findings lies in the possibility that ultrasound-guided costoclavicular space approach, with its enhanced precision and patient outcomes, could play a pivotal role in improving upper limb surgical procedures.

A novel framework reveals anthropogenic stressors of phosphorus polluted river-lake connection water system in Poyang lake basin of China.

Poyang lake (PYL), as China's largest freshwater lake, has been suffering from increasing total phosphorus (TP) pollution associated with rapid basinal socio-economic development. However, anthropogenic phosphorus stressors were rarely examined in PYL basin due to its large-scale and complex river-lake connection water system, hampering phosphorus pollution control efforts. In this study, water pollution stress from multiple anthropogenic activities is quantitatively examined in PYL basin based on a newly developed framework coupling grey water footprint (GWF) analysis with the SPARROW model. Results show that the phosphorus source-sink process in PYL basin has been well simulated by SPARROW model quantifying an overall TP delivery rate of 0.39, with catchments closer to PYL showing higher delivery rate of phosphorus (up to over 0.8). The GWF analysis demonstrates that anthropogenic phosphorus sources have imposed much higher pollution stress on PYL than its inflowing rivers, with twelve catchments nearby PYL identified as critical source areas of TP contamination. Agricultural farming, livestock & poultry production, and urban household are recognized as the dominant anthropogenic stressors burdening water environment of PYL. Based on these, policy recommendations are provided for advancing control of the phosphorus pollution stressors. The methodology is effective in refined examination of water pollution sources, which is expected to be applied in other watersheds providing informative diagnosis of water issues especially in lakes.

Development and application of a multiplex qPCR assay for the detection of duck circovirus, duck Tembusu virus, Muscovy duck reovirus, and new duck reovirus.

A multiplex qPCR assay was developed to simultaneously detect duck circovirus (DuCV), duck Tembusu virus (DTMUV), Muscovy duck reovirus (MDRV), and novel duck reovirus (NDRV), but it did not amplify other viruses, including duck virus enteritis (DVE), infectious bursal disease virus (IBDV), avian reovirus (ARV), H5 avian influenza virus (H5 AIV), H7 avian influenza virus (H7 AIV), H9 avian influenza virus (H9 AIV), Newcastle disease virus (NDV), and Muscovy duck parvovirus (MDPV), and the detection limit for DuCV, DTMUV, MDRV, and NDRV was 1.51 × 101 copies/µL. The intra- and interassay coefficients of variation were less than 1.54% in the repeatability test with standard plasmid concentrations of 1.51 × 107, 1.51 × 105, and 1.51 × 103 copies/µL. The developed multiple qPCR assay was used to examine 404 clinical samples to verify its practicability. The positivity rates for DuCV, DTMUV, MDRV, and NDRV were 26.0%, 9.9%, 4.0%, and 4.7%, respectively, and the mixed infection rates for DuCV + DTMUV, DuCV + MDRV, DuCV + NDRV, MDRV + NDRV, DTMUV + MDRV, and DTMUV + NDRV were 2.7%, 1.2%, 1.2%, 1.0%, 0.5%, and 0.7%, respectively.

Isolation and characterization of a novel parvovirus from a red-crowned crane, China, 2021.

BACKGROUND: Parvoviruses are icosahedral, nonenveloped viruses with single-stranded DNA genomes of approximately 5 kb in length. In recent years, parvoviruses have frequently mutated and expanded their host range to cause disease in many wild animals by altering their tissue tropism. Animal infection mainly results in acute enteritis and inflammation of other organs. In this study, we used a viral metagenomic method to detect a novel parvovirus species in a red-crowned crane that died due to severe diarrhea in China. RESULTS: The presence of the viral genome in the kidney, lung, heart, liver, and intestine were confirmed by PCR. Histopathological examination of the intestine showed a large number of infiltrated inflammatory cells. The JL21/10 strain of the red-crowned crane parvovirus was first isolated from the intestine. Whole-genome sequence analysis showed that JL21/10 shared high identity with the red-crowned crane Parvovirinae strains yc-8 at the nucleotide level (96.61%). Phylogenetic analysis of the complete genome and NS1 gene revealed that the JL21/10 strain clustered with strains in chicken and revealed a close genetic relationship with the red-crowned crane parvovirus strains.The complete of VP2 gene analysis showed that JL21/10 shared identity with the red-crowned crane yc-8 strains (97.7%), chicken (55.4%),ducks(31.0%) and geese(30.1%) at the amino acid level. The result showed that red-crowned crane parvovirus may be cross-species transmission to chicken. However, There is little possibility of transmission to ducks and geese. CONCLUSION: This is the first isolation and identification of a parvovirus in red-crowned crane that was associated with severe diarrhea.

Outcome and associated factors of high-risk human papillomavirus infection without cervical lesions.

OBJECTIVE: To study the outcome of human papillomavirus (HPV) infection in women with cervical pathology results of non-cervical intraepithelial neoplasia (CIN) or cervical cancer and positive high-risk HPV test, as well as analyze the associated risk factors affecting the outcome of infection. METHODS: To investigate the outcome of high-risk (HR)-HPV infection in the female genital tract and analyze the associated risk factors affecting their outcome, a total of 196 women with positive HR-HPV test results and non-CIN or cervical cancer cervical pathology results were selected for follow-up at the Cervical Disease Clinic of the Obstetrics and Gynecology Hospital, Zhejiang University School of Medicine from January 2017 to March 2020. The follow-up interval was every 6 months, and both cervical cytology (TCT) and HR-HPV testing were performed at each follow-up visit. If the cervical cytology results were normal upon recheck and the HR-HPV test was negative, the woman was considered to be cleared of the HPV infection and was entered into the routine cervical screening population. When the repeat HR-HPV test remained positive after 6 months, the woman was defined as having a persistent HR-HPV infection. If HR-HPV persisted but the TCT results were normal, follow-up was continued. If HR-HPV persisted and the TCT results were abnormal, a colposcopy-guided biopsy was performed immediately. In this situation, if the histological results were still non-CIN or cervical cancer, the follow-up was continued. If the histological results confirmed the development of CIN or invasive cancer, then enter another study follow-up to further track its development and outcome, and the woman commenced the treatment process. The HPV infection clearance time was analyzed by the Kaplan-Meier method, and the comparison of the HPV clearance rate and infection clearance time between each of the different groups was performed using aχ2 test or Fisher's exact test, as appropriate. After the univariate analysis, several significant factors were included in the Cox model and independent risk factors were analyzed. RESULTS: A total of 163 women were enrolled in this study. The median age was 40.0 years (22-67 years) and the median follow-up time was 11.5 months (6-31 months). The spontaneous clearance rate of HR-HPV infection was 51.5%, and the median time to viral clearance was 14.5 months. Age and the initial viral load were high risk factors affecting the spontaneous clearance of HR-HPV infection. The factors significantly associated with HPV clearance rate and time to HPV clearance consisted of menopause and full-term delivery (P < 0.05). CONCLUSIONS: In women with normal or low-grade lesions on the cell smear, the spontaneous clearance rate of HR-HPV infection was 51.5% and the time to clearance was 14.5 months. Age and the initial viral load were independent associated factors affecting the spontaneous clearance of HR-HPV infection in the female genital tract. These findings suggest that non-young women or those with high viral loads have a higher rate of persistent HR-HPV infection. Thus, intensive screening should be recommended.

Acute Coronary Syndrome May be Associated with Decreased Resolvin D1-to-Leukotriene B4 Ratio.

An imbalance between inflammation-resolving lipid mediators and proinflammatory leukotrienes with the instability of atherosclerotic plaques in experimental models has been reported. However, the contribution of the balance of Resolvin D1 (RvD1) to Leukotriene B4 (LTB4) in predicting acute coronary syndrome (ACS) remains unknown. This study investigated the association of RvD1-to-LTB4 ratio with ACS.Eighty-one patients with ACS and 90 stable coronary artery disease (SCAD) patients were included in this study. Plasma RvD1 and LTB4 levels were measured with commercial kits.Patients with ACS had higher LTB4 levels, lower RvD1 levels, and a lower RvD1-to-LTB4 ratio than patients with SCAD. History of diabetes mellitus, elevated Troponin I, LTB4, and decreased RvD1-to-LTB4 ratio (odds ratio [OR]: 1.025; 95% confidence interval [CI]: 1.014-1.040; P < 0.001) were independently correlated with ACS. Receiver operating characteristic curve analysis demonstrated that RvD1-to-LTB4 ratio was a potential biomarker for the risk of ACS.A circulating proinflammatory lipid profile, characterized by a low RvD1-to-LTB4 ratio may be associated with ACS in patients with ischemic heart disease.

Analgesic Effects of Ropivacaine Combined With Dexmedetomidine in Transversus Abdominis Plane Block in Patients Undergoing Laparoscopic Cholecystectomy: A Systematic Review and Meta-Analysis.

PURPOSE: This review aimed to conduct a meta-analysis of published randomized controlled studies (RCTs) comparing the effectiveness of dexmedetomidine (DEX) combined with ropivacaine versus single ropivacaine in transversus abdominis plane block (TAPB) for postoperative analgesia after laparoscopic cholecystectomy (LC). The purpose was to investigate whether DEX combined with ropivacaine in TAPB for postoperative analgesia in LC is superior to single ropivacaine administration. DESIGN: A Systematic Review and Meta-analysis. METHODS: Five electronic database systems were searched for RCTs on the effects of DEX combined with ropivacaine (joint group) and single ropivacaine on postoperative analgesia in LC. The standardized mean difference (SMD) or odds ratio (OR) and their corresponding 95% confidence interval (CI) of the indicators were calculated for comparison. FINDINGS: As of December 23, 2021, 153 articles were retrieved, but only 16 articles were finally included in this meta-analysis. The results showed that compared with single ropivacaine, DEX combined with ropivacaine in TAPB had better analgesia and lighter sedative effect in patients after LC. After LC 2h(T1), 4h(T2), 8h(T3), 12h(T4) and 24h (T5), the joint group participants have lower VAS scores (T1: SMD = -0.32, 95%CI: -0.49, -0.14; T2: SMD = -1.11, 95%CI: -1.56, -0.65; T3: SMD = -2.88, 95%CI: -3.74, -2.02; T4: SMD = -2.56, 95%CI: -3.04, -2.08; T5: SMD = -1.44, 95%CI: -1.81, -1.06). Also, the Ramsay score of the joint group is higher than the single group (T1: SMD = 1.05, 95%CI: 0.39, 1.71; T2: SMD = 1.57, 95%CI: 0.57, 2.57; T3: SMD = 1.64, 95%CI: 0.65, 2.63; T4: SMD = 1.72, 95%CI: 0.54, 2.89; T5: SMD = 0.57, 95%CI: 0.21, 0.94). CONCLUSIONS: The results of this review and meta-analysis suggest that DEX combined with ropivacaine has less postoperative pain, more patients got the status of sober and cooperative, and longer postoperative analgesia lasted than ropivacaine alone in TAPB, especially in the group of combined treatment with 1.0 mcg/kg DEX. Furthermore, the flow dynamics of the two groups are stable, and there is no notable difference in the incidence of adverse reactions.

Evaluating the influence of different environmental water allocation schemes on the water level of a typical shallow lake in semiarid regions: From the perspective of an integrated modeling approach.

Many lakes in semiarid regions around the world rely on environmental water allocation to maintain the health of the lake ecosystem. However, under changing environments, the competition for water resources between human society and natural ecosystems has intensified. How to manage environmental water allocation more reasonably and precisely has become an important issue. The largest lake on the North China Plain, Baiyangdian Lake (BYDL), is a typical lake facing such challenges. To provide feasible strategies for sustainable water allocation to BYDL, with the proper parameterization of hydrological processes, this study developed a 10-day temporal scale lake water level prediction model to quantify how environmental water allocation regulates the BYDL water level under different hydroclimatic conditions. Evaluation of model performance revealed that environmental water allocation rather than natural climatic periodicity dominates the variation in the BYDL water level. The model structure could be further improved with consideration of more detailed observations of both the surface runoff entering BYDL and the water area beneath the canopy of the reeds in BYDL. Analysis of 72 model simulation scenarios indicated that water allocations from multiple sources are indispensable and that the water resources that guarantee maintaining the BYDL water level within the ecologically suitable range vary substantially under different hydroclimatic conditions. More elaborate allocation plans are required both to improve the water quality and health of the aquatic ecosystem of BYDL and to reduce the risk of flooding. The findings from this study are valuable for guiding the implementation of environmental water allocations to lakes in semiarid regions worldwide.

Assessing alterations of water level due to environmental water allocation at multiple temporal scales and its impact on water quality in Baiyangdian Lake, China.

Lakes in arid/semiarid regions face problems of insufficient inflow and degradation of water quality, which threaten the health of the lake ecosystem. Baiyangdian Lake (BYDL), the largest lake in the North China Plain, is confronted with such challenges. The objective of this study was to improve understanding of how changes in water level influence water quality in the BYDL at different temporal scales, especially related to implementations of intermittent environmental water allocation activities in the past two decades, by using data on monthly lake water level, climate factors of precipitation and temperature, and lake water quality. The Mann-Kendall method and continuous wavelet analysis revealed that the lake water level shows a significant decreasing trend after 1967, and the period of 16-year was identified as the principal period for 1950-2018. Based on cross-wavelet transform and wavelet coherence analysis, the periodic agreement and coherence between water level and climatic factors decreased after 1997, when environmental water allocations started, indicating that the influences of climatic factors, i.e., precipitation and temperature, became weak. By utilizing the cross-wavelet transform and wavelet coherence analysis methods, the relationships between lake water level and water quality parameters of chemical oxygen demand, ammonia nitrogen, total nitrogen, and total phosphorus were investigated. We found that the change in source and amount of environmental water allocation is one possible reason for the temporal evolution in joint variability between lake water level and water quality. Meanwhile, a dilution effect of freshwater allocated to BYDL was detected in the time-frequency domain. However, the result also indicates that the driving mechanism of water quality is complex due to the combined impacts of water allocation, nonpoint source pollution in the rainy season, and nutrient release from lake sediment. Our findings improve the general understanding of changes in water level in lakes located in arid and semiarid regions under climate change and intensive human activities, and also provide valuable knowledge for decision making in aquatic ecosystem restoration of BYDL and other similar lakes.

2000 PPI silicon-based AlGaInP red micro-LED arrays fabricated via wafer bonding and epilayer lift-off.

In this article, 2000 PPI red silicon-based AlGaInP micro-LED arrays were fabricated and investigated. The AlGaInP epilayer was transferred onto the silicon substrate via the In-Ag bonding technique and an epilayer lift-off process. The silicon substrate with a high thermal conductivity could provide satisfactory heat dissipation, leading to micro-LED arrays that had a stable emission spectrum with increasing current density from 20 to 420 A/cm2 along with a red-shift of the peak position from 624.69 to 627.12 nm (Δλ = 2.43 nm). Additionally, increasing the injection current density had little effect on the CIE (x, y) of the micro-LED arrays. Further, the I-V characteristics and light output power of micro-LED arrays with different pixel sizes demonstrated that the AlGaInP red micro-LED array on a silicon substrate had excellent electrical stability and optical output.

Comparative genomics analysis of strains from diverse sources reveals the evolutionary relationship of Aeromonas veronii.

Aeromonas veronii (A. veronii, AV) strains are emerging zoonotic and aquatic pathogens, yet we know very little about their genomics. This study aims to utilize comparative genomics to investigate the intraspecific genetic diversity, differences in virulence factors and evolutionary mechanisms of A. veronii strains from diverse sources and to fundamentally demonstrate their pathogenic mechanisms. We conducted comparative genomics analysis of 39 A. veronii strains from different sources and found that 1993 core genes are shared by these strains and that these shared core genes may be necessary to maintain the basic characteristics of A. veronii. Additionally, phylogenetic relationship analysis based on these shared genes revealed that a distant relationship between the AMC34 strain and the other 38 strains but that, the genetic relationship among the 38 strains is relatively close, indicating that AMC34 may not belong to A. veronii. Furthermore, analysis of shared core genes and average nucleotide identity (ANI) values showed no obvious correlation with the location of A. veronii isolation and genetic relationship. Our research indicates the evolutionary mechanism of A. veronii from different sources and provides new insights for a deeper understanding of its pathogenic mechanism.

Ezetimibe Improves Rosuvastatin Effects on Inflammation and Vascular Endothelial Function in Acute Coronary Syndrome Patients Undergoing PCI.

BACKGROUND: Little is known of the acute effects of ezetimibe in patients with acute coronary syndrome (ACS) undergoing PCI. We investigated whether ezetimibe improves inflammation and vascular endothelial function in patients with ACS undergoing PCI. METHODS: We randomized 171 patients with ACS undergoing PCI to receive ezetimibe 10 mg/day plus rosuvastatin 20 mg/day (combination group, n = 81) versus rosuvastatin 20 mg/day (rosuvastatin group, n = 90). Lipid profile, type II secretory phospholipase A2 (sPLA2-IIa), interleukin-1ß (IL-1ß), vascular cell adhesion molecule-1 (VCAM-1), and intercellular cell adhesion molecule-1 (ICAM-1) were measured at baseline and after 7 days. Three months after PCI, clinical outcomes were examined. RESULT: The levels of sPLA2-IIa and IL-1ß reduced significantly in both groups, but more when ezetimibe and rosuvastatin were coadministered (sPLA2-IIa: 6.16 ± 2.67 vs. 7.42 ± 3.53 ng/ml, p=0.01; IL-1ß: 37.39 ± 26.25 vs. 48.98 ± 32.26 pg/ml, p=0.01). A significant rise of VCAM-1 and ICAM-1 was observed on day 7 after PCI in the both groups, but was less in the combination group (VCAM-1: 918.28 ± 235.31 vs. 988.54 ± 194.41 ng/ml, p=0.03; ICAM-1: 213.01 ± 100.15 vs. 246.88 ± 105.71 ng/ml, p=0.03). Patients in the combination versus rosuvastatin group appeared to suffer from less major adverse events. Periprocedural therapy of ezetimibe improves rosuvastatin effects on proinflammatory responses and endothelial function associated with ACS patients undergoing PCI. This trial is registered with https://clinicaltrials.gov/ct2/show/ChiCTR-IPR-17012219 (Chinese Clinical Trial Registry, http://www.chictr.org.cn on 02/08/2017).

First detection and complete genome analysis of the Lyon IARC polyomavirus in China from samples of diarrheic cats.

Lyon IARC polyomavirus (LIPyV), a newly discovered polyomavirus (PyV), was first identified in 2017 in human skin samples in the USA. Later, it was detected in several other countries in samples of human and feline origin. Our aim was to find out if the virus occurs in China. To this end, 100 fecal samples were collected from cats with diarrhea in Guangxi Province during 2016 and 2018 and tested with polymerase chain reaction (PCR). Only 2 samples that originated from two related individuals were found to be positive. Based on the sequence identity of the 240-bp PCR products, the two positive samples supposedly contained identical viruses. Therefore, only one of them, which was designated as LIPyV-GXNN01, was selected for full genome amplification, cloning, sequencing and analysis. LIPyV-GXNN01, which comprises 5,263 nucleotides, has an early region that consists of small T antigen (ST-Ag) and large T antigen (LT-Ag) and a late region coding for the VP1, VP2, and VP3 structural proteins. Moreover, the LIPyV-GXNN01 strain structural proteins share 95.9-99.4%, 97.6-99.2%, and 97.1-99.2% nucleic acid identity with the VP1, VP2, and VP3of other LIPyV reference strains, respectively. A phylogenetic analysis revealed that GXNN01 clustered together with previously reported LIPyV strain. This present study is the first report of LIPyV in China.

4-Methylumbelliferyl glucuronide contributes to hyaluronan synthesis inhibition.

4-Methylumbelliferone (4-MU) inhibits hyaluronan (HA) synthesis and is an approved drug used for managing biliary spasm. However, rapid and efficient glucuronidation is thought to limit its utility for systemically inhibiting HA synthesis. In particular, 4-MU in mice has a short half-life, causing most of the drug to be present as the metabolite 4-methylumbelliferyl glucuronide (4-MUG), which makes it remarkable that 4-MU is effective at all. We report here that 4-MUG contributes to HA synthesis inhibition. We observed that oral administration of 4-MUG to mice inhibits HA synthesis, promotes FoxP3+ regulatory T-cell expansion, and prevents autoimmune diabetes. Mice fed either 4-MUG or 4-MU had equivalent 4-MU:4-MUG ratios in serum, liver, and pancreas, indicating that 4-MU and 4-MUG reach an equilibrium in these tissues. LC-tandem MS experiments revealed that 4-MUG is hydrolyzed to 4-MU in serum, thereby greatly increasing the effective bioavailability of 4-MU. Moreover, using intravital 2-photon microscopy, we found that 4-MUG (a nonfluorescent molecule) undergoes conversion into 4-MU (a fluorescent molecule) and that 4-MU is extensively tissue bound in the liver, fat, muscle, and pancreas of treated mice. 4-MUG also suppressed HA synthesis independently of its conversion into 4-MU and without depletion of the HA precursor UDP-glucuronic acid (GlcUA). Together, these results indicate that 4-MUG both directly and indirectly inhibits HA synthesis and that the effective bioavailability of 4-MU is higher than previously thought. These findings greatly alter the experimental and therapeutic possibilities for HA synthesis inhibition.

An epidemiological investigation of porcine circovirus 3 infection in cattle in Shandong province, China.

BACKGROUND: Porcine circovirus type 3 (PCV3) is a single-stranded, closed circular DNA virus, which causes porcine dermatitis and nephropathy syndrome (PDNS), multisystemic inflammation, and reproductive failure. The present study aimed to investigate the seroprevalence of PCV3 in cattle (Bos taurus) in Shandong province, China, and examine its genome diversity. RESULTS: PCR amplification and sequencing showed that 74 of 213 bovine samples (34.7%) were positive for PCV3. Among them, the capsid gene (n = 12) and the complete genome (n = 4) were sequenced. These sequences had high identities to the reference capsid gene (98.0-100%) and the complete genome (97.5-99.8%). The PCV3 strains were classified into two different genotypes (PCV3a and PCV3b), according to phylogenetic analysis based on the complete genome and capsid gene sequences. Specifically, the bovine-origin strains in this study were grouped into PCV3a, showing a close relationship with PCV3-US/SD2016 (American strain; GenBank: KX966193.1). Notably, a comparison of the inferred amino acid sequences revealed a mutation from D124 to Y124. CONCLUSION: This was the first seroprevalence and genetic investigation of PCV3 in cattle in Shandong province, China. The results could provide insights into the epidemiology and pathogenesis of this important virus.

Impacts of macrophage colony-stimulating factor (M-CSF) on the expression of natriuretic peptide precursor type C (NPPC) and regulation of meiotic resumption.

In mammalian follicles, oocytes are arrested at the diplotene stage of prophase I until meiotic resumption following the LH surge. C-type natriuretic peptide (CNP), encoded by natriuretic peptide precursor type C (NPPC), was found to be reduced by the LH surge in the follicle, and then lead to meiotic resumption by decreasing the level of cAMP in the oocyte. As a wide-spread cytokine, macrophage colony-stimulating factor (M-CSF) takes part in the oocyte development to maturation and ovulation. Our study describes the expression curve of M-CSF and its receptor and investigates the impact on the levels of CNP/NPPC to explore the possible mechanism for meiotic resumption in both vivo and vitro. The result shows after the LH/HCG surge, the expressions of M-CSF and its receptors decline significantly inside ovarian follicles, thus leading to transduction of a range of signals. Consequently, the expression of CNP reaches the peak at 2 h and immediately declines to a relatively low level.