Adenovirus-mediated sphingomyelin synthase 2 increases atherosclerotic lesions in ApoE KO mice

<p>Abstract</p> <p>Background</p> <p>Sphingomyelin synthase 2 (SMS2) contributes to de novo sphingomyelin (SM) biosynthesis. Its activity is related to SM levels in the plasma and the cell membrane. In this study, we investigated the possibility of a direct relationship between SMS and atherosclerosis.</p> <p>Methods</p> <p>The Adenovirus containing SMS2 gene was given into 10-week ApoE KO C57BL/6J mice by femoral intravenous injection. In the control group, the Adenovirus containing GFP was given. To confirm this model, we took both mRNA level examination (RT-PCR) and protein level examination (SMS activity assay).</p> <p>Result</p> <p>We generated recombinant adenovirus vectors containing either human SMS2 cDNA (AdV-SMS2) or GFP cDNA (AdV-GFP). On day six after intravenous infusion of 2 × 10¹¹particle numbers into ten-week-old apoE KO mice, AdV-SMS2 treatment significantly increased liver SMS2 mRNA levels and SMS activity (by 2.7-fold, 2.3-fold, p < 0.001, respectively), compared to AdV-GFP treated mice. Moreover, plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and sphingomyelin (SM) levels were significantly increased by 39% (p < 0.05), 42% (p < 0.05), 68% (p < 0.001), and 45% (p < 0.05), respectively. Plasma high-density lipoprotein cholesterol (HDL-C), phosphatidylcholine (PC), and PC/SM ratio were decreased by 42% (p < 0.05), 18% (p < 0.05), and 45% (p < 0.05), respectively. On day 30, the atherosclerotic lesions on the aortic arch of AdV-SMS2 treated mice were increased, and the lesion areas on the whole aorta and in the aortic root were significantly increased (p < 0.001). Furthermore, the collagen content in the aorta root was significantly decreased (p < 0.01).</p> <p>Conclusions</p> <p>Our results present direct morphological evidence for the pro-atherogenic capabilities of SMS2. SMS2 could be a potential target for treating atherosclerosis.</p

Anorexia nervosa and bulimia nervosa: a Mendelian randomization study of gut microbiota

BackgroundAnorexia nervosa (AN) and bulimia nervosa (BN) poses a significant challenge to global public health. Despite extensive research, conclusive evidence regarding the association between gut microbes and the risk of AN and BN remains elusive. Mendelian randomization (MR) methods offer a promising avenue for elucidating potential causal relationships.Materials and methodsGenome-wide association studies (GWAS) datasets of AN and BN were retrieved from the OpenGWAS database for analysis. Independent single nucleotide polymorphisms closely associated with 196 gut bacterial taxa from the MiBioGen consortium were identified as instrumental variables. MR analysis was conducted utilizing R software, with outlier exclusion performed using the MR-PRESSO method. Causal effect estimation was undertaken employing four methods, including Inverse variance weighted. Sensitivity analysis, heterogeneity analysis, horizontal multivariate analysis, and assessment of causal directionality were carried out to assess the robustness of the findings.ResultsA total of 196 bacterial taxa spanning six taxonomic levels were subjected to analysis. Nine taxa demonstrating potential causal relationships with AN were identified. Among these, five taxa, including Peptostreptococcaceae, were implicated as exerting a causal effect on AN risk, while four taxa, including Gammaproteobacteria, were associated with a reduced risk of AN. Similarly, nine taxa exhibiting potential causal relationships with BN were identified. Of these, six taxa, including Clostridiales, were identified as risk factors for increased BN risk, while three taxa, including Oxalobacteraceae, were deemed protective factors. Lachnospiraceae emerged as a common influence on both AN and BN, albeit with opposing effects. No evidence of heterogeneity or horizontal pleiotropy was detected for significant estimates.ConclusionThrough MR analysis, we revealed the potential causal role of 18 intestinal bacterial taxa in AN and BN, including Lachnospiraceae. It provides new insights into the mechanistic basis and intervention targets of gut microbiota-mediated AN and BN

The establishment and application of a dual Nano-PCR detection method for feline calicivirus and feline herpesvirus type I

Feline calicivirus (FCV) and Feline herpesvirus type I (FHV-I) are the main pathogens causing upper respiratory tract infections in cats, and some wild animals. These two viruses always coinfection and cause serious harm to pet industry and wild animals protection. Established a rapid and accurate differential diagnosis method is crucial for prevention and control of disease, however, the current main detection method for these two viruses, either is low sensitivity (immunochromatographic strip), or is time-consuming and cannot differential diagnosis (conventional single PCR). Nanoparticle-assisted polymerase chain reaction (Nano-PCR) is a recently developed technique for rapid detection method of virus and bacteria. In this study, we described a dual Nano-PCR assay through combining the nanotechnology and PCR technology, which for the clinical simultaneous detection of FCV and FHV-I and differential diagnosis of upper respiratory tract infections in cats or other animals. Under optimized conditions, the optimal annealing temperature for dual Nano-PCR was 51.5°C, and specificity test results showed it had no cross reactivity to related virus, such as feline panleukopenia virus (FPV), feline Infectious peritonitis virus (FIPV) and rabies virus (RABV). Furthermore, the detection limit of dual Nano-PCR for FCV and FHV-I both were 1 × 10−8 ng/μL, convert to number of copies of virus DNA was 6.22 × 103copies/μL (FCV) and 2.81 × 103copies/μL (FHV-I), respectively. The dual Nano-PCR detected result of 52 cat clinical samples, including ocular, nasal and faecal swabs, and (3 FCV-positive samples), was consistent with ordinary PCR and the clinical detection results. The dual Nano-PCR method established in this study with strong specificity and high sensitivity can be used for virus nucleic acid (FCV and FHV-I) detection of clinical samples of feline upper respiratory tract infections feline calicivirus and feline herpesvirus while providing support for the early diagnosis of cats that infected by FCV and FHV-I

The impact of external plant carbon sources on nitrogen removal and microbial community structure in vertical flow constructed wetlands

The present study was developed to explore nitrogen removal performance and associated microbial mechanisms of action in vertical flow constructed wetlands (VFCWs) when using external carbon sources. These analyses ultimately revealed that alkali-soaked Phragmites australis (P. australis) could serve as an effective plant carbon source, exhibiting the lower levels of total nitrogen (TN) release and the highest chemical oxygen demand (COD) of all tested carbon sources. Nitrogen removal efficiency improved following the addition of plant carbon sources, and under carbon/nitrogen (C/N) rations of 2, 4, 5, and 7, the VFCW system was able to remove 43.69%–75.76% TN, with the highest removal rate being observed at a C/N of 5. The abundance of denitrifying microorganisms such as Thiobaillus and Halomonas were also more enriched in VFCW1 than VFCW0, with stronger correlations in the microbial network community. A qPCR approach was used to analyze functional genes involved in denitrification, revealing that the addition of plant carbon sources was associated with increases in total gene abundance and the abundance of the denitrifying gene nirS, whereas no corresponding increase in amoA or nxrA abundance was observed. Higher total gene, amoA, and nxrA abundance were observed in the upper levels of these VFCW systems as compared to the lower layers, whereas nirS exhibited the opposite abundance pattern. Overall, these findings suggested that short-range denitrification is likely to be the primary denitrification process active in this VFCW system

Mapping the path towards novel treatment strategies: a bibliometric analysis of Hashimoto’s thyroiditis research from 1990 to 2023

BackgroundHashimoto’s thyroiditis (HT), a common form of thyroid autoimmunity, is strongly associated with deteriorating clinical status and impaired quality of life. The escalating global prevalence, coupled with the complexity of disease mechanisms, necessitates a comprehensive, bibliometric analysis to elucidate the trajectory, hotspots, and future trends in HT research.ObjectiveThis study aims to illuminate the development, hotspots, and future directions in HT research through systematic analysis of publications, institutions, authors, journals, references, and keywords. Particular emphasis is placed on novel treatment strategies for HT and its complications, highlighting the potential role of genetic profiling and immunomodulatory therapies.MethodsWe retrieved 8,726 relevant documents from the Web of Science Core Collection database spanning from 1 January 1990 to 7 March 2023. Following the selection of document type, 7,624 articles were included for bibliometric analysis using CiteSpace, VOSviewer, and R software.ResultsThe temporal evolution of HT research is categorized into three distinct phases: exploration (1990-1999), rapid development (1999-2000), and steady growth (2000-present). Notably, the United States, China, Italy, and Japan collectively contributed over half (54.77%) of global publications. Among the top 10 research institutions, four were from Italy (4/10), followed by China (2/10) and the United States (2/10). Recent hotspots, such as the roles of gut microbiota, genetic profiling, and nutritional factors in HT management, the diagnostic dilemmas between HT and Grave’s disease, as well as the challenges in managing HT complicated by papillary thyroid carcinoma and type 1 diabetes mellitus, are discussed.ConclusionAlthough North America and Europe have a considerable academic impact, institutions from emerging countries like China are demonstrating promising potential in HT research. Future studies are anticipated to delve deeper into the differential diagnosis of HT and Grave’s disease, the intricate relationship between gut microbiota and HT pathogenesis, clinical management of HT with papillary thyroid carcinoma or type 1 diabetes, and the beneficial effects of dietary modifications and micronutrients supplementation in HT. Furthermore, the advent of genetic profiling and advanced immunotherapies for managing HT offers promising avenues for future research

Targeting FGFR4 Inhibits Hepatocellular Carcinoma in Preclinical Mouse Models

The fibroblast growth factor (FGF)-FGF receptor (FGFR) signaling system plays critical roles in a variety of normal developmental and physiological processes. It is also well documented that dysregulation of FGF-FGFR signaling may have important roles in tumor development and progression. The FGFR4–FGF19 signaling axis has been implicated in the development of hepatocellular carcinomas (HCCs) in mice, and potentially in humans. In this study, we demonstrate that FGFR4 is required for hepatocarcinogenesis; the progeny of FGF19 transgenic mice, which have previously been shown to develop HCCs, bred with FGFR4 knockout mice fail to develop liver tumors. To further test the importance of FGFR4 in HCC, we developed a blocking anti-FGFR4 monoclonal antibody (LD1). LD1 inhibited: 1) FGF1 and FGF19 binding to FGFR4, 2) FGFR4–mediated signaling, colony formation, and proliferation in vitro, and 3) tumor growth in a preclinical model of liver cancer in vivo. Finally, we show that FGFR4 expression is elevated in several types of cancer, including liver cancer, as compared to normal tissues. These findings suggest a modulatory role for FGFR4 in the development and progression of hepatocellular carcinoma and that FGFR4 may be an important and novel therapeutic target in treating this disease

Fused Deposition Modeling of Single-Use Plastic Alloy

Packaging plastics are called ‘single-use plastics’ because of short lifetime. Among which, the three plastics of polyethylene (PE), polypropylene (PP), and polyethylene terephthalate (PET) take more than 70%. Due to incompatibility, few research has been done on the alloy of the three plastics. The aim of this study is to investigate the possibility of single-use plastic alloy (SUPA) of ternary PE, PP, and PET as the 3D printing material. Tensile and bending tests are carried out to investigate the mechanical properties, photographs of scanning electron microscope (SEM) are taken for morphology analysis, and differential scanning calorimetry (DSC) are used to study the crystallization behavior of the alloys. The results show that there is an optimal ratio for all the components to obtain the best mechanical performances, i.e., the ratio of PP / PE = 40 / 60 with 20 wt% PET, 2 wt% maleic anhydride grafted polypropylene (PP-g-MAH) and 2 wt% organic modified montmorillonite (OMMT). This SUPA has a tensile strength of 14.48 MPa, a tensile modulus of 586.42 MPa, a flexural strength of 15.85 MPa, and a flexural modulus of 544.67 MPa. Due to the function of compatibilizer and nanoclay (NC) will be affected by redundancy, the potential primary fibrosis while collecting the feeding filaments and the secondary fibrosis at the nozzle of 3D printing might be responsible for the variation of the mechanical performances.</jats:p

Fused Deposition Modeling of Single-Use Plastic Alloy

Packaging plastics are called ‘single-use plastics’ because of short lifetime. Among which, the three plastics of polyethylene (PE), polypropylene (PP), and polyethylene terephthalate (PET) take more than 70%. Due to incompatibility, few research has been done on the alloy of the three plastics. The aim of this study is to investigate the possibility of single-use plastic alloy (SUPA) of ternary PE, PP, and PET as the 3D printing material. Tensile and bending tests are carried out to investigate the mechanical properties, photographs of scanning electron microscope (SEM) are taken for morphology analysis, and differential scanning calorimetry (DSC) are used to study the crystallization behavior of the alloys. The results show that there is an optimal ratio for all the components to obtain the best mechanical performances, i.e., the ratio of PP/PE=40/60 with 20 wt% PET, 2 wt% maleic anhydride grafted polypropylene (PP-g-MAH) and 2 wt% organic modified montmorillonite (OMMT). This SUPA has a tensile strength of 14.48 MPa, a tensile modulus of 586.42 MPa, a flexural strength of 15.85 MPa, and a flexural modulus of 544.67 MPa. Due to the function of compatibilizer and nanoclay (NC) will be affected by redundancy, the potential primary fibrosis while collecting the feeding filaments and the secondary fibrosis at the nozzle of 3D printing might be responsible for the variation of the mechanical performances