Potential Use of Serum Proteomics for Monitoring COVID-19 Progression to Complement RT-PCR Detection.

RT-PCR is the primary method to diagnose COVID-19 and is also used to monitor the disease course. This approach, however, suffers from false negatives due to RNA instability and poses a high risk to medical practitioners. Here, we investigated the potential of using serum proteomics to predict viral nucleic acid positivity during COVID-19. We analyzed the proteome of 275 inactivated serum samples from 54 out of 144 COVID-19 patients and shortlisted 42 regulated proteins in the severe group and 12 in the non-severe group. Using these regulated proteins and several key clinical indexes, including days after symptoms onset, platelet counts, and magnesium, we developed two machine learning models to predict nucleic acid positivity, with an AUC of 0.94 in severe cases and 0.89 in non-severe cases, respectively. Our data suggest the potential of using a serum protein-based machine learning model to monitor COVID-19 progression, thus complementing swab RT-PCR tests. More efforts are required to promote this approach into clinical practice since mass spectrometry-based protein measurement is not currently widely accessible in clinic.

KIF18b-dependent hypomethylation of PARPBP gene promoter enhances oxaliplatin resistance in colorectal cancer.

As the new platinum drug oxaliplatin has been widely used in clinical treatment of colorectal cancer (CRC), oxaliplatin resistance has become a burning problem. In this study, higher expression of PARP-1 binding protein (PARPBP) was detected in oxaliplatin-resistant CRC (OR-CRC) cells than in non-resistant cells. Further research showed that kinesin family member 18 b (KIF18b) induced the overexpression of PARPBP, sustaining oxaliplatin resistance in OR-CRC cells. Through exploring the PARPBP gene promoter, we found that SP1-recruited DNMT3b methylated PARPBP promoter to suppress transcription in CRC cells, and increased KIF18b attenuated the recruitment of DNMT3b to PARPBP promoter by directly interacting with SP1 in OR-CRC cells. Clinical analysis suggested a positive relationship between KIF18b and PARPBP in CRC tissues and indicated poor prognosis in CRC patients with high level of KIF18b or PARPBP. In summary, KIF18b-induced PARPBP contributes to the resistant phenotype of OR-CRC.

Investigation of the feasibility of NRAV as a biomarker for hepatocellular carcinoma.

The long non-coding RNA, Negative Regulator of Antiviral Response (NRAV) has been identified as a participant in both respiratory virus replication and immune checkpoints, however, its involvement in pan-cancer immune regulation and prognosis, particularly those of hepatocellular carcinoma (HCC), remains unclear. To address this knowledge gap, we analyzed expression profiles obtained from The Cancer Genome Atlas (TCGA) database, comparing normal and malignant tumor tissues. We found that NRAV expression is significantly upregulated in tumor tissues compared to adjacent nontumor tissues. Kaplan-Meier (K-M) analysis revealed the prognostic power of NRAV, wherein overexpression was significantly linked to reduced overall survival in a diverse range of tumor patients. Furthermore, noteworthy associations were observed between NRAV, immune checkpoints, immune cell infiltration, genes related to autophagy, epithelial-mesenchymal transition (EMT), pyroptosis, tumor mutational burden (TMB), and microsatellite instability (MSI) across different cancer types, including HCC. Moreover, NRAV upregulation expression was associated with multiple pathological stages by clinical observations. Furthermore, our investigation revealed a substantial elevation in the expression of NRAV in both HCC tumor tissues and cells compared to normal tissues and cells. The inhibition of NRAV resulted in the inhibition of cell proliferation, migration, and invasion in HCC cells, while also influencing the expression of CD274 (PD-L1) and CD44, along with various biomarkers associated with EMT, autophagy, and pyroptosis. The aforementioned results propose NRAV as a promising prognostic biomarker for HCC.

Modeling the Wintering Habitat Distribution of the Black Stork in Shaanxi, China: A Hierarchical Integration of Climate and Land Use/Land Cover Data.

Species distribution models (SDMs) are effective tools for wildlife conservation and management, as they employ the quantification of habitat suitability and environmental niches to evaluate the patterns of species distribution. The utilization of SDMs at various scales in a hierarchical approach can provide additional and complementary information, significantly improving decision-making in local wildlife conservation initiatives. In this study, we considered the appropriate spatial scale and data resolution to execute species distribution modeling, as these factors greatly influence the modeling procedures. We developed SDMs for wintering black storks at both the regional and local scales. At the regional scale, we used climatic and climate-driven land use/land cover (LULC) variables, along with wintering occurrence points, to develop models for mainland China. At the local scale, we used local environmental variables and locally gathered wintering site data to develop models for Shaanxi province. The predictions from both the regional and local models were then combined at the provincial level by overlapping suitable areas based on climatic and local conditions. We compared and evaluated the resulting predictions using seven statistical metrics. The national models provide information on the appropriate climatic conditions for the black stork during the wintering period throughout China, while the provincial SDMs capture the important local ecological factors that influence the suitability of habitats at a finer scale. As anticipated, the national SDMs predict a larger extent of suitable areas compared to the provincial SDMs. The hierarchical prediction approach is considered trustworthy and, on average, yields better outcomes than non-hierarchical methods. Our findings indicate that human-driven LULC changes have a significant and immediate impact on the wintering habitat of the black stork. However, the effects of climate change seem to be reducing the severity of this impact. The majority of suitable wintering habitats lie outside the boundaries of protected areas, highlighting the need for future conservation and management efforts to prioritize addressing these conservation gaps and focusing on the protection of climate refuges.

UPLC-MS/MS-based plasma lipidomics reveal a distinctive signature in systemic lupus erythematosus patients.

Global lipidomics is of considerable utility for exploring altered lipid profiles and unique diagnostic biomarkers in diseases. We aim to apply ultra-performance liquid chromatography-tandem mass spectrometry to characterize the lipidomics profile in systemic lupus erythematosus (SLE) patients and explore the underlying pathogenic pathways using the lipidomics approach. Plasma samples from 18 SLE patients, 20 rheumatoid arthritis (RA) patients, and 20 healthy controls (HC) were collected. A total of 467 lipids molecular features were annotated from each sample. Orthogonal partial least square-discriminant analysis, K-mean clustering analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated disrupted lipid metabolism in SLE patients, especially in phospholipid, glycerol, and sphingolipid metabolism. The area under curve (AUC) of lipid metabolism biomarkers was better than SLE inflammation markers that ordinarily used in the clinic. Proposed model of monoglyceride (MG) (16:0), MG (18:0), phosphatidylethanolamine (PE) (18:3-16:0), PE (16:0-20:4), and phosphatidylcholine (PC) (O-16:2-18:3) yielded AUC 1.000 (95% CI, 1.000-1.000), specificity 100% and sensitivity 100% in the diagnosis of SLE from HC. A panel of three lipids molecular PC (18:3-18:1), PE (20:3-18:0), PE (16:0-20:4) permitted to accurately diagnosis of SLE from RA, with AUC 0.921 (95% CI, 0.828-1.000), 70% specificity, and 100% sensitivity. The plasma lipidomics signatures could serve as an efficient and accurate tool for early diagnosis and provide unprecedented insight into the pathogenesis of SLE.

Acacetin Protects Myocardial Cells against Hypoxia-Reoxygenation Injury through Activation of Autophagy.

Ischemic heart disease is a leading cause of mortality and morbidity worldwide. We previously demonstrated that acacetin protects against myocardial ischemia reperfusion injury in rats, although the underlying mechanism remains to be elucidated. In the present study, we investigated the effects of acacetin on autophagy during hypoxia/reoxygenation (H/R) injury by exposing H9c2 myocardial cells to H/R with or without acacetin pretreatment during hypoxia. Our results show that acacetin significantly increased cell viability in a dose-dependent manner, enhanced antioxidant capacity, and suppressed protein apoptosis of rat cardiomyocytes H9c2 cells following H/R injury. In addition, lentiviral infection of H9c2 cardiomyocytes revealed that acacetin pretreatment significantly enhanced the fluorescence intensity of autophagy proteins Beclin 1, LC3-II, and p62. These results indicate that acacetin protected H9c2 cardiomyocytes from H/R damage by enhancing autophagy. Moreover, we found that application of acacetin increased activation of the PI3K/Akt signaling pathway, whereas cotreatment with the PI3K inhibitor LY294002 reversed the inhibition of apoptosis and autophagy induced by acacetin. In conclusion, acacetin mitigated H/R injury by promoting autophagy through activating the PI3K/Akt/mTOR signaling pathway.

Mycobacterial identification on homogenised biopsy facilitates the early diagnosis and treatment of laryngeal tuberculosis.

INTRODUCTION: The incidence of laryngeal tuberculosis has increased gradually in recent years. Laryngeal tuberculosis has strong infectivity and atypical clinical manifestations. Hence, establishing the early diagnosis of laryngeal tuberculosis is considered difficult, resulting in the high rate of misdiagnosis of laryngeal tuberculosis and increased rates of tuberculosis infection. OBJECTIVE: This study aimed to describe a case of laryngeal tuberculosis detected using the mycobacteria gene chips technology, facilitating the early diagnosis and the treatment of laryngeal tuberculosis. CASE PRESENTATION: A 27-year-old woman presented with a 7-day history of hoarseness, with a normal routine blood chemistry test and chest computed tomography results. Histological analysis of the vocal cord biopsy showed granulomatous inflammation and the negative acid-fast stain test. The mycobacteria gene chips method was used to directly examine the vocal cord tissue treated with homogenate, and the Mycobacterium tuberculosis was successfully identified. Thus, the early diagnosis of laryngeal tuberculosis and the drug sensitivity of rifampin and isoniazid were confirmed. The patient recovered after undergoing a 1-year standard anti-tuberculosis therapy. CONCLUSIONS: Mycobacterial identification on homogenised biopsy using the mycobacteria gene chips method significantly facilitates the early diagnosis and the treatment of tuberculosis.

Evaluation of droplet digital PCR for quantification of SARS-CoV-2 Virus in discharged COVID-19 patients.

The worldwide severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak has led to the rapid spread of coronavirus disease (COVID-19). The quantitative real time PCR (qPCR) is widely used as the gold standard for clinical detection of SARS-CoV-2. However, more and more infected patients are relapsing after discharge, which suggests qPCR may fail to detect the virus in some cases. In this study, we selected 74 clinical samples from 43 recovering inpatients for qPCR and Droplet Digital PCR (ddPCR) synchronous blind detection, and established a cutoff value for ddPCR diagnosis of COVID-19. The results showed that at a cutoff value of 0.04 copies/µL, the ddPCR sensitivity and specificity are 97.6% and 100%, respectively. In addition, we also analyzed 18 retained samples from 9 discharged patients who relapsed. Although qPCR showed all 18 samples to be negative, ddPCR showed 12 to be positive, and there was only one patient with two negative samples; the other eight patients had at least one positive sample. These results indicate that ddPCR could significantly improve the accuracy of COVID-19 diagnosis, especially for discharged patients with a low viral load, and help to reduce misdiagnosis during recovery.

Clinical evaluation of a rapid colloidal gold immunochromatography assay for SARS-Cov-2 IgM/IgG.

BACKGROUND: Since December 2019, there had been an outbreak of COVID-19 in Wuhan, China. At present, diagnosis COVID-19 were based on real-time RT-PCR, which have to be performed in biosafe laboratory and is unsatisfactory for suspect case screening. Therefore, there is an urgent need for rapid diagnostic test for COVID-19. OBJECTIVE: To evaluate the diagnostic performance and clinical utility of the colloidal gold immunochromatography assay for SARS-Cov-2 specific IgM/IgG anti-body detection in suspected COVID-19 cases. METHODS: In the prospective cohort, 150 patients with fever or respiratory symptoms were enrolled in Taizhou Public Health Medical Center, Taizhou Hospital, Zhejiang province, China, between January 20 to February 2, 2020. All patients were tested by the colloidal gold immunochromatography assay for COVID-19. At least two samples of each patient were collected for RT-PCR assay analysis, and the PCR results were performed as the reference standard of diagnosis. Meanwhile 26 heathy blood donor were recruited. The sensitivity and specificity of the immunochromatography assay test were evaluated. Subgroup analysis were performed with respect to age, sex, period from symptom onset and clinical severity. RESULTS: The immunochromatography assay test had 69 positive result in the 97 PCR-positive cases, achieving sensitivity 71.1% [95% CI 0.609-0.797], and had 2 positive result in the 53 PCR-negative cases, achieving specificity 96.2% [95% CI 0.859-0.993]. In 26 healthy donor blood samples, the immunochromatography assay had 0 positive result. In subgroup analysis, the sensitivity was significantly higher in patients with symptoms more than 14 days 95.2% [95% CI 0.741-0.998] and patients with severe clinical condition 86.0% [95% CI 0.640-0.970]. CONCLUSIONS: The colloidal gold immunochromatography assay for SARS-Cov-2 specific IgM/IgG anti-body had 71.1% sensitivity and 96.2% specificity in this population, showing the potential for a useful rapid diagnosis test for COVID-19. Further investigations should be done to evaluate this assay in variety of clinical settings and populations.

Over-expression of CD200 predicts poor prognosis in MDS.

BACKGROUND: We studied the expression of CD200 in a series of 101 patients with diagnosis of myelodysplastic syndrome (MDS), to evaluate its impact on outcome and its possible association with other known prognostic factors. MATERIAL/METHODS: The CD200 was detected by flow cytometry, and the chromosome karyotypes were determined by G banding respectively. The Mann-Whitney U test was used to analyze the association among CD200 expression and clinical features. In addition, the overall survival and AML transformation of the MDS patients according to the expression level of CD200 was also explored. RESULTS: Overall, the flow cytometric analyses confirmed that expression of CD200 was high in this patient cohort compared to normal BM (p<0.01). The levels of CD200 in RCUD (20.3%±4.3%), RCMD (25.0%±4.5%), RAEB-1 (39.2%±4.9%), and RAEB-2 (43.2%±5.8%) groups were obviously higher than that of RARS group (6.8%±1.7%, P<0.05). Significant differences of CD200 expression were observed in the 4 groups of MDS according to IPSS risk(P<0.01). After 45-month follow-up, Kaplan-Meier analysis of patients with MDS in our study indicated that patients with high expression level of CD200 had a shorter overall survival and a high Leukemic transformation than those with low expression (p<0.01). CONCLUSIONS: In conclusion, our findings provide firstly the evidence that CD200 is up-regulated and emerging as both a prognostic factor and a potential target of novel therapeutic approaches for MDS.