Correlation Analysis and Diagnostic Value of Serum Homocysteine, Cystatin C and Uric Acid Levels with the Severity of Coronary Artery Stenosis in Patients with Coronary Heart Disease.

Background: Coronary angiography (CAG) is an invasive examination with high risks and costs and various complications may occur. It is necessary to find a diagnostic method, non-invasiveness, inexpensive with low risk. This study aims to analyze the correlation between the levels of serum homocysteine (Hcy), cystatin C (Cys C) and uric acid (UA) and Gensini score in patients with coronary heart disease (CHD) and assess their diagnostic value for CHD. Methods: A retrospective analysis was conducted on 1412 patients underwent CAG from October 2019 to December 2021, and we conducted this study from January to July 2022. A total of 765 patients with CHD confirmed by CAG were selected as the research group, while 647 patients revealed as non-obstructive stenosis by CAG as the control group. The serum Hcy, Cys C and UA levels were detected and the correlation between Gensini score and variables was analyzed. The receiver-operating characteristic (ROC) curve was performed to assess the diagnostic value of the Hcy, Cys C and UA for CHD. Results: The serum Hcy, Cys C and UA levels in the research group were higher as compared with the control group (p<0.05). Spearman correlation and multivariate linear regression analysis showed that there was a significantly positive correlation between Gensini score and serum Hcy, Cys C and UA levels (p<0.05). The ROC curve analysis presented the combined Hcy and Cys C with UA having the highest specificity of diagnostic value for CHD (area under the curve (AUC)=0.768, 95% CI 0.706-0.823, specificity = 72.34%, sensitivity = 67.88%, Youden Index = 0.4022). Conclusion: The serum Hcy, Cys C and UA levels in patients with CHD were significantly increased, positive correlation with Gensini score. The combined Hcy and Cys C with UA could be used to assess the severity of coronary artery stenosis and provide predictive and early intervention treatment values for CHD and a new way of diagnosing CHD, which is cheap, safe, effective and deserving of clinical application.

Decreased echinocandin susceptibility in Candida parapsilosis causing candidemia and emergence of a pan-echinocandin resistant case in China.

Candida parapsilosis is becoming a predominant non-albicans cause of invasive candidiasis (IC). Echinocandins are the preferred choice for IC treatment and prophylaxis. Resistance to echinocandins in C. parapsilosis has emerged in several countries, but little is known about the susceptibility profile in China or about mechanisms of resistance. Here, we investigated the echinocandin susceptibilities of 2523 C. parapsilosis isolates collected from China and further explored the resistance mechanism among echinocandin-resistant isolates. Anidulafungin exhibited the highest MICs (MIC50/90, 1 and 2 µg/mL; GM, 0.948 µg/mL), while caspofungin showed better activity (0.5 and 1 µg/mL; 0.498 µg/mL). Significantly higher echinocandin MICs were observed among blood-derived isolates compared to others, especially for caspofungin (GM, 1.348 µg/mL vs 0.478 µg/mL). Isolates from ICU and surgical wards also showed higher MICs. Twenty isolates showed intermediate phenotypes for at least one echinocandin. One was resistant to all three echinocandins, fluconazole and voriconazole, which caused breakthrough IC during long-term exposure to micafungin. WGS revealed this isolate carried a mutation S656P in hotspot1 region of Fks1. Bioinformatics analyses suggested that this mutation might lead to an altered protein conformation. CRISPR Cas9-mediated introduction of this mutation into a susceptible reference C. parapsilosis strain increased MICs of all echinocandins 64-fold, with similar results found in the subspecies, C. orthopsilosis and C. metapsilosis. This is the first report of a multi-azole resistant and pan-echinocandin resistant C. parapsilosis isolate, and the identification of a FKS1S656P conferring pan-echinocandin resistance. Our study underscores the necessity of rigorous management of antifungal use and of monitoring for antifungal susceptibility.

MiR-10a-5p-Mediated Syndecan 1 Suppression Restricts Porcine Hemagglutinating Encephalomyelitis Virus Replication.

Porcine hemagglutinating encephalomyelitis virus (PHEV) is a single-stranded RNA coronavirus that causes nervous dysfunction in the infected hosts and leads to widespread alterations in the host transcriptome by modulating specific microRNA (miRNA) levels. MiRNAs contribute to RNA virus pathogenesis by promoting antiviral immune response, enhancing viral replication, or altering miRNA-mediated host gene regulation. Thus, exploration of the virus-miRNA interactions occurring in PHEV-infected host may lead to the identification of novel mechanisms combating the virus life cycle or pathogenesis. Here, we discovered that the expression of miR-10a-5p was constitutively up-regulated by PHEV in both the N2a cells in vitro and mice brain in vivo. Treatment with miR-10a-5p mimics allowed miR-10a-5p enrichment and resulted in a significant restriction in PHEV replication, suggesting widespread negative regulation of the RNA virus infection by miR-10a-5p. The outcomes were also evidenced by miR-10a-5p inhibitor over-expression. Luciferase reporter, quantitative real-time PCR (qRT-PCR), and western blotting analysis further showed that Syndecan 1 (SDC1), a cell surface proteoglycan associated with host defense mechanisms, acts as a target gene of miR-10a-5p during PHEV infection. Naturally, siRNA-mediated knockdown of SDC1 leads to a reduction in viral replication, implying that SDC1 expression is likely a favorable condition for viral replication. Together, the findings demonstrated that the abundant miR-10a-5p leads to downstream suppression of SDC1, and it functions as an antiviral mechanism in the PHEV-induced disease, providing a potential strategy for the prevention and treatment of PHEV infection in the future work.

Effects of 20-day litter weight on weaned piglets' fighting behavior after group mixing and on heart rate variability in an isolation test.

OBJECTIVE: The objective of this study was to investigate the effect of 20-day litter weight on behavior and heart rate variability (HRV) of piglets under stress. METHODS: Forty four original litters were categorized as high litter weight (HW) litters (n = 22) and low litter weight (LW) litters (n = 22) by 20-day litter weight. From each original HW litter, three males and three females were randomly selected after weaning and the 12 piglets from two original litters with similar age of days were regrouped into one new high litter weight (NHW) litter (11 NHW litters in total). The original LW litters were treated with a same program, so that there were 11 new low litter weight (NLW) litters as well. The latencies to first fighting, fighting frequencies and duration within three hours were recorded after regrouping and the lesions on body surface within 48 hours were scored. Besides, HR (heart rate, bpm, beats per minute) and activity count (ACT), time domain indexes and frequency domain indexes of the piglets were measured in an isolation trial to analyze the discrepancy in coping with stress between the original HW and LW litters. RESULTS: The results exhibited that piglets from the HW litters launched fighting sooner and got statistically higher skin lesion score than those from the LW litters (p = 0.03 and 0.02, respectively). Regarding the HRV detection, compared with the HW litters, the LW litters exhibited a lower mean HR (p<0.05). In the isolation test, a highly significant higher ACT value was observed between the HW litters, compared to the LW litters (p<0.01). Significant differences were observed in standard deviation of R-R intervals, standard deviation of all normal to normal intervals, and most frequency-domain indicators: very low-frequency, low-frequency, and high frequency between the HW and LW litters as well. The difference in LF:HF was not significant (p = 0.779). CONCLUSION: This study suggests that compared with litters of low 20-day litter weights, litters with higher 20-day litter weight take more positive strategies to cope with stress and have stronger HRV regulation capacity; HW litters demonstrate better anti-stress and adaptation capacity in the case of regrouping and isolation.

Myo10 is required for neurogenic cell adhesion and migration.

Myosin X (Myo10), an untraditional member of myosin superfamily, is characterized as an actin-based molecular motor, which plays a critical role in diverse cellular motile events. Previous research by our group has found that Myo10 influenced neuronal radial migration in developing neocortex, but the underlying mechanism is still largely unknown. In this study, we found that knockdown of endogenous Myo10 in a normal gonadotropin-releasing hormone (GnRH) neuronal cell line transfected with the large T antigen (NLT) induced the impairment of cell motility and orientation. In the wound healing assay, with the Golgi complex staining to display cell polarity, Myo10 knockdown cells were randomly oriented compared to the control. Furthermore, suppressing the expression of Myo10 decreased the ability of cell-matrix adhesion. N-cadherin, a calcium-dependent classical cell adhesion molecule, rescued the migration deficiency caused by Myo10 knockdown in cell aggregates and collagen gel assay. These results suggest that Myo10 is required for neurogenic cell migration through N-cadherin mediated cell adhesion.

Both Myosin-10 isoforms are required for radial neuronal migration in the developing cerebral cortex.

During embryonic development of the mammalian cerebral cortex, postmitotic cortical neurons migrate radially from the ventricular zone to the cortical plate. Proper migration involves the correct orientation of migrating neurons and the transition from a multipolar to a mature bipolar morphology. Herein, we report that the 2 isoforms of Myosin-10 (Myo10) play distinct roles in the regulation of radial migration in the mouse cortex. We show that the full-length Myo10 (fMyo10) isoform is located in deeper layers of the cortex and is involved in establishing proper migration orientation. We also demonstrate that fMyo10-dependent orientation of radial migration is mediated at least in part by the netrin-1 receptor deleted in colorectal cancer. Moreover, we show that the headless Myo10 (hMyo10) isoform is required for the transition from multipolar to bipolar morphologies in the intermediate zone. Our study reveals divergent functions for the 2 Myo10 isoforms in controlling both the direction of migration and neuronal morphogenesis during radial cortical neuronal migration.

Involvement of headless myosin X in the motility of immortalized gonadotropin-releasing hormone neuronal cells.

Myosin X (Myo X), an unconventional myosin with a tail homology 4-band 4.1/ezrin/radixin/moesin (MyTH4-FERM) tail, is expressed ubiquitously in various mammalian tissues. In addition to the full-length Myo X (Myo X FL), a headless form is synthesized in the brain. So far, little is known about the function of this motor-less Myo X. In this study, the role of the headless Myo X was investigated in immortalized gonadotropin-releasing hormone (GnRH) neuronal cells, NLT. NLT cells overexpressing the headless Myo X formed fewer focal adhesions and spread more slowly than the wild-type NLT cells and GFP-expressing NLT cells. In chemomigration assays, the NLT cells overexpressing the headless Myo X migrated shorter distances and had fewer migratory cells compared with the control NLT cells.