Adenosine Deaminase as a Potential Diagnostic and Prognostic Biomarker for Severe Fever with Thrombocytopenia Syndrome.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a serious infectious disease caused by the Dabie bandavirus, with a high mortality rate. Currently, there are no effective vaccines or specific treatments for SFTS. Early diagnosis and accurate severity assessment are crucial. METHODS: This study included 171 cases of SFTS, COVID-19, and hepatitis B virus (HBV) patients and healthy controls. We compared the serum adenosine deaminase (ADA) activity across these groups. The diagnostic and prognostic efficiency of serum ADA for SFTS was evaluated by using receiver operating characteristic (ROC) curve analysis. We also examined the correlation between serum ADA in SFTS patients and clinical lab parameters as well as serum cytokines. RESULTS: SFTS patients had significantly higher serum ADA activity than those of COVID-19, HBV patients, and healthy controls. Nonsurvivor SFTS patients had notably higher ADA than survivors. ROC analysis indicated ADA as an effective SFTS diagnostic and prognostic biomarker. ADA correlated with prognosis, viral load, APTT, PT, AST, ferritin, negatively with HDL-c and LDL-c, and positively with cytokines like IL-6, TNF-α, and IL-1ß. Multiorgan failure patients showed significant ADA increase. CONCLUSION: Elevated serum ADA activity in SFTS patients is linked with disease severity and prognosis, showing potential as a diagnostic and prognostic biomarker for SFTS.

Prevention of the Lachnum polysaccharide and its selenium derivatives on cisplatin-induced acute kidney injury in mice.

To investigate the renal protective effects of the polysaccharide LEP-1a and derivatives of selenium (SeLEP-1a) from Lachnum YM38, cisplatin (CP) was used to establish an acute kidney model. LEP-1a and SeLEP-1a could effectively reverse the decrease in renal index and improved renal oxidative stress. LEP-1a and SeLEP-1a significantly reduced the contents of the inflammatory cytokines. They could inhibit the release of cyclooxygenase 2 (COX-2) and nitric oxide synthase (iNOS) and increase the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1). At the same time, the PCR results indicated that SeLEP-1a could significantly inhibit the mRNA expression levels of toll-like receptor 4 (TLR4), nuclear factor-kB (NF-κB) p65 and inhibitor of kappa B-alpha (IκBα). Western blot analysis showed that LEP-1a and SeLEP-1a significantly downregulated the expression levels of Bcl-2-associated X protein (Bax) and cleaved caspase-3 and upregulated phosphatidylinositol 3-kinase (p-PI3K), protein kinase B (p-Akt) and B-cell lymphoma 2 (Bcl-2) protein expression levels in the kidney. LEP-1a and SeLEP-1a could improve CP-induced acute kidney injury by regulating the oxidative stress response, NF-κB-mediated inflammation and the PI3K/Akt-mediated apoptosis signalling pathway.

Association of low HDL-c levels with severe symptoms and poor clinical prognosis in patients with severe fever and thrombocytopenia syndrome.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an acute infectious disease caused by a novel bunyavirus, characterized by high fever, thrombocytopenia, and multiple organ damage. Disturbances in lipid metabolism often occur during viral infections, but the changes and clinical significance of lipid profiles in SFTS patients remain unclear. This study aimed to investigate the alterations in lipid profiles and their clinical significance in SFTS patients. Methods: A total of 157 SFTS patients and 157 healthy controls were enrolled in this study. Serum lipid levels were collected and analyzed among different groups and prognosis categories. Receiver operating characteristic (ROC) curve analysis was performed to assess the ability of lipid levels in distinguishing between severe and mild cases, as well as surviving and non-surviving patients. Pearson correlation analysis was used to examine the associations between lipid levels and clinical laboratory parameters. Results: SFTS patients exhibited significantly lower levels of HDL-c, LDL-c, cholesterol, APoAI, and ApoB compared to healthy controls, while triglyceride levels were significantly higher. Serum HDL-c and ApoAI demonstrated good performance as indicators for distinguishing between survivors and non-survivors (AUC of 0.87 and 0.85, respectively). Multivariate regression analysis indicated that HDL-c independently acts as a protective factor in patients with SFTS. HDL-c levels showed decline in non-survivors but recovered in survivors. Moreover, HDL-c exhibited significant correlations with various clinical laboratory parameters (IL-6, CRP, AST, TT, APTT, PLT, ALB, and CD4). Conclusion: This study identified abnormalities in serum lipid metabolism among SFTS patients. HDL-c and ApoAI levels hold potential as biomarkers for distinguishing survivors from non-survivors. Additionally, HDL-c and ApoAI may serve as therapeutic targets for the management of SFTS patients.

Correlation of serum adenosine deaminase activity with disease activity in patients with primary Sjögren's syndrome.

BACKGROUND: Primary Sjögren's syndrome (pSS) is a chronic inflammatory autoimmune disease primarily affecting the exocrine glands, which has a variety of clinical manifestations and unclear pathogenic mechanisms. Adenosine deaminase (ADA) is an enzyme involved in the breakdown of purines, and changes in its activity have been associated with a number of autoimmune diseases. This study aims to investigate the relationship between serum ADA activity and disease activity in patients with pSS. METHODS: In this study, 196 patients with pSS and 196 healthy controls were enrolled. Serum ADA activity and clinical laboratory parameters were collected and analyzed in both groups. Pearson correlation analysis was used to examine the correlation between ADA activity and clinical laboratory parameters, as well as the correlation between ADA activity and the disease activity score. RESULTS: Compared with healthy controls, the activity of ADA in the serum of pSS patients was significantly increased (P < 0.0001), and the ADA activity was significantly decreased after immunosuppressive treatment (P < 0.0001). Correlation analysis revealed that the activity of ADA was significantly positively correlated with erythrocyte sedimentation rate (ESR) (r = 0.3, P < 0.0001) and serum immunoglobulin G (IgG) levels (r = 0.5, P < 0.0001), and significantly negatively correlated with high-density lipoprotein (HDL) (r = -0.4, P < 0.0001). Furthermore, there was a significant positive correlation between ADA activity and the disease activity score as measured by the Sjögren's Syndrome Disease Activity Index (SSDAI) (r = 0.4, P < 0.0001). CONCLUSION: This study found that patients with pSS have higher activity of ADA in serum, which is associated with disease activity as measured by SSDAI. These results suggest that ADA activity may be a potential biomarker for evaluating disease activity and treatment efficacy in pSS patients. Additionally, ADA may be a potential target for the treatment of pSS patients.

Role of adenosine A2a receptor in cancers and autoimmune diseases.

Adenosine receptors are P1 class of purinergic receptors that belong to G protein-coupled receptors. There are 4 subtypes of adenosine receptors, namely A1, A2A, A2B, and A3. A2AR has a high affinity for the ligand adenosine. Under pathological conditions or external stimuli, ATP is sequentially hydrolyzed to adenosine by CD39 and CD73. The combination of adenosine and A2AR can increase the concentration of cAMP and activate a series of downstream signaling pathways, and further playing the role of immunosuppression and promotion of tumor invasion. A2AR is expressed to some extent on various immune cells, where it is abnormally expressed on immune cells in cancers and autoimmune diseases. A2AR expression also correlates with disease progression. Inhibitors and agonists of A2AR may be potential new strategies for treatment of cancers and autoimmune diseases. We herein briefly reviewed the expression and distribution of A2AR, adenosine/A2AR signaling pathway, expression, and potential as a therapeutic target.

The investigation of the NH3-SCR performance of a copper-based AEI-CHA intergrown zeolite catalyst.

This work prepared an ISAPO-34/SAPO-18 intergrown zeolite using phosphate organoamine as the structure guiding agent. Physical-chemical characterizations by XRD, SEM, TG, and BET showed that the SAPO-34/SAPO-18 presents a cross-stacked cubic block-like microscopic morphology, with characteristic diffusive diffraction peaks at 2θ = 16-18° and 30-33° and a specific surface area of 557 m2 g-1. The series of copper-based catalysts prepared from SAPO-34/SAPO-18 showed a shift of the active temperature window to a lower temperature with increasing copper content. Moreover, the Brønsted acid site decreased significantly due to copper ion exchange and zeolite structure framework damage. Among them, the 1.2 wt% sample showed the widest active temperature window, with a T90 range of 175-435°C. After low-temperature hydrothermal aging treatment, the zeolite structure was eroded and the catalyst activity deteriorated significantly.

Topology Optimization for Hybrid Lattice Compliant Mechanisms with Multiple Microstructures.

Hybrid lattice compliant mechanisms (HLCMs) composed of multiple microstructures have attracted widespread interest due to their superior compliant performance compared to the traditional solid compliant mechanisms. A novel optimization scheme for HLCMs is presented using the independent continuous mapping (ICM) method. Firstly, the effective properties of multiple orthogonal and anisotropic lattice microstructures are obtained by taking advantage of homogenization theory, which are used to bridge the relationship between the macrostructure layout and microstructure recognition. Then, a new parallel topology optimization model for optimizing HLCMs is built via a generalized multi-material, recognizing interpolation scheme with filter functions. In addition, the characterization relationship between independent continuous variables and performance of different elements is established. Sensitivity analysis and linear programming are utilized to solve the optimal model. Lastly, numerical examples with a displacement inverter mechanism and compliant gripper mechanism demonstrate the effectiveness of the proposed method for designing HLCMs with various lattice microstructures. Anisotropic lattice microstructures (ALMs) significantly facilitate the efficient use of constitutive properties of materials. Hence, HLCMs consisting of various ALMs achieve superior compliant performance than counterparts comprising different orthogonal lattice microstructures (OLMs). The presented method offers a reference to optimize HLCMs, as well as promotes the theoretical development and application of the ICM method.

Polysaccharides from Lachnum sp. Inhibited colitis-associated colon tumorigenesis in mice by modulating fecal microbiota and metabolites.

It is still uncertain whether the consumption of Lachnum sp. polysaccharides (LEP) alleviates colorectal cancer (CRC) through the gut microbiota. In this study, our efforts are focused on the influence of LEP on CRC, intestinal barrier and inflammation, and fecal microbiota and the metabolites, in azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CRC mice. Results showed that LEP inhibited CRC mouse colon shortening and weight loss, decreased tumor incidence, restored intestinal barrier integrity, and reduced excessive inflammation. LEP consumption significantly altered microbiota overall structure and community, with reduced pernicious bacteria (such as Parabacteroides, Escherichia_Shigella, Desulfovibrio and Helicobacter), and increased beneficial bacterium (such as Alistipes, Alloprevotella and Ruminiclostridium). Fecal-metabolome profile indicated that a total of 43 metabolites were clearly changed, with 10 down-regulated and 33 up-regulated metabolites. In addition, short-chain fatty acids (SCFAs), including acetic acid, propionic acid and n-butyric acid, were significantly increased after LEP administration. Moreover, a strong correlation between the fluctuant gut microbiota and metabolites was found. These findings provided not only deeper insights into the responsibility of LEP for CRC alleviation, and but also the potential of LEP as a promising candidate for CRC prevention and treatment.

Investigation of the spatial heterogeneity of soil microbial biomass carbon and nitrogen under long-term fertilizations in fluvo-aquic soil.

Soils are heterogeneous and microbial spatial distribution can clearly indicate the spatial characteristics of the soil carbon and nitrogen cycle. However, it is not clear how long-term fertilization affects the spatial distribution of microbial biomass in fluvo-aquic soil. We collected fluvo-aquic soil samples (topsoil 0-7.5 cm and sub-topsoil 7.5-20 cm) using a spatially-explicit design within three 40.5 m2 plots in each of four fertilization treatments. Fertilization treatments were: cropping without fertilizer inputs (CK); chemical nitrogen, phosphorus, and potassium fertilizer (NPK); chemical fertilizer with straw return (NPKS); and chemical fertilizer with animal manure (NPKM). Variables included soil microbial biomass carbon (MBC) and nitrogen (MBN), and MBC/MBN. For both soil layers, we hypothesized that: microbial biomass was lowest in CK but with the largest spatial heterogeneity; and microbial biomass was highest in NPKM and NPKS but with the lowest spatial heterogeneity. Results showed that: (1) Fertilization significantly increased MBC and MBN more in topsoil than sub-topsoil but had no MBC/MBN changes. (2) The coefficient of variation (CV) and Cochran's C showed that variation was largest in CK in topsoil and NPK in sub-topsoil and that variation of topsoil was generally lower than in sub-topsoil. The sample size of the three variables was largest in CK in topsoil but had little variation among the other treatments. (3) The trend-surface model showed that within-plot heterogeneity varied substantially with fertilization (NPKM = NPK > NPKS > CK), but Moran's I and the interpolation map showed that spatial variability with fertilization followed the order NPK > NPKS > CK = NPKM at a fine scale in topsoil. In sub-topsoil, the trend-surface model showed that within-plot heterogeneity followed the order NPKM = CK > NPK > NPKS and that the fine-scale pattern was NPKM>NPK = NPKS>CK. MBC had the highest spatial heterogeneity among the three variables in both soil layers. Our results indicate that the application of organic fertilizer (straw or manure) reduced the variation of MBC and MBN but increased the spatial variability of MBC and MBN. The spatial variation of the three variables was MBC > MBN > MBC/MBN regardless of whether variation was considered at the plot-scale or the fine-scale in both layers.

Protective effects of a Lachnum polysaccharide against liver and kidney injury induced by lead exposure in mice.

This study was designed to investigate the liver and kidney protective efficacy of a Lachnum polysaccharide (LEP) against Pb-induced toxicity in mice. The results showed that LEP decreased the Pb-induced bodyweight loss and organ index. Moreover, biochemical analysis showed that treatment of LEP could improve antioxidant status (CAT, GSH-Px and MDA) and the injury of tissues (liver and kidney). In addition, the histopathological observations indicated that LEP could attenuate liver and kidney cell injury induced by Pb. For further studies, key proteins involved in hepatic and kidney apoptosis, including cleaved caspase-3, Bax, Bcl-2, TGF-ß1 and α-SMA, were quantified. The present findings demonstrated that LEP is strongly effective in protecting against the liver and kidney injury induced by Pb. We hope this research can offer a theoretical base for development of polysaccharide based on nutraceutical food in future.

Predictive of 21-gene recurrence score assay in non-estrogen receptor-positive and lymph node-negative breast cancer.

PURPOSE: The 21-gene recurrence score (RS) assay predicts relapse of estrogen receptor-positive and lymph node-negative breast cancer more accurately than traditional markers; however, whether this assay can be regarded as a molecular marker of other types of breast cancer is unclear. We aimed to identify the effect of 21-gene recurrence score assay in non-estrogen receptor-positive and lymph node-negative breast cancer. METHODS: We analyzed 21-gene expression by quantitative real-time PCR (qRT-PCR) in 100 cases of breast cancer tissues and followed up for 5 years to investigate the prognostic significance in non-estrogen receptor-positive and lymph node-negative breast cancer. Also, the correlation between RS and the clinicopathological features were analyzed. Adjuvant online (AOL) database was used for the analyses in the present study. RESULTS: The cases were classified as RS low (n=52), moderate (n=22) and high (n=26) risk. The RS based on the21-gene assay was not correlated with age, tumor size, histological grade, and lymph node and estrogen receptor/progesterone receptor (ER/PR) status; however, there was significant correlation with Her-2 status. The 5-year recurrence rates were 1.92%, 4.55% and 15.38% in the low, moderate and high-risk groups, respectively. In addition, there was significant difference between the low-high groups (p<0.05). Furthermore, the consistency of the prognosis predicted by the AOL system was 56% and 59% in the RS moderate-high risk and low risk groups, respectively. CONCLUSIONS: The 21-gene RS assay was a prognostic indicator for patients with non-ER-positive and lymph node-negative breast cancer. In addition, our results coincided with those obtained using the AOL system.

Anticoagulant activity of a sulfated Lachnum polysaccharide in mice with a state of hypercoagulability.

A sulfated polysaccharide, designated as SLEP-1, was obtained after sulfation of the exopolysaccharide (LEP-1) which was isolated from Lachnum. The degree of substitution (DS) of sulfate group of SLEP-1 was 1.97. SEM images of SLEP-1 revealed laminated structure in mesh. UV, FT-IR and 13C NMR spectra indicated that the LEP-1 was sulfated successfully. The result of the anticoagulant activity in vitro showed that both of LEP-1 and SLEP-1 could effectively prolong activated partial thromboplastin time (APTT) and thrombin time (TT) of the normal mice plasma, in which SLEP-1 was more effectively than those of LEP-1, and dose-effect relationships were found. According to the bleeding time (BT), clotting time (CT), APTT, PT, prothrombin time (TT), fibrinogen (FIB), AT-III activity and FXa concentration of the hypercoagulable mice, it indicated that SLEP-1 (30mg·kg-1 and 90mg·kg-1) had strong inhibitory effect on intrinsic coagulation pathway, which could also enhance fibrinolytic activity. It may constitute an anticoagulant drug of interest in anticoagulant therapy.

Polymorphisms in thymidylate synthase and reduced folate carrier (SLC19A1) genes predict survival outcome in advanced non-small cell lung cancer patients treated with pemetrexed-based chemotherapy.

The aim of this study was to evaluate the association between thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR) and reduced folate carrier (SLC19A1) gene polymorphisms and the treatment efficacy of pemetrexed-based chemotherapy in advanced non-small cell lung cancer (NSCLC). Advanced NSCLC patients received pemetrexed and cisplatin every three weeks. Polymorphisms in the TS, MTHFR and SLC19A1 genes were detected in peripheral blood samples using DNA sequencing and Taqman PCR. An analysis of gene polymorphisms was performed with respect to the progression-free survival (PFS), response rate (RR) and overall survival (OS) of patients treated with pemetrexed. The median PFS times for patients with the TS 2R/2R, 2R/3C or 3C/3C genotypes were significantly longer than those of patients with the 2R/3G, 3C/3G or 3G/3G genotypes (P=0.036). Patients with the SLC19A1 CC genotype had a significantly longer median OS compared with individuals with the homozygous and heterozygous genotypes (12.2 vs. 8.9 and 7.3 months, respectively; P=0.022). The PFS and OS did not differ for the three genotypes of MTHFR assessed. The RR was higher in patients with the TS 2R/2R, 2R/3C or 3C/3C genotypes than in the other groups (P=0.044). The polymorphisms of the 5'-UTR of the TS gene and exon 6 (2522) C/T of the SLC19A1 gene predict the survival of advanced NSCLC patients treated with pemetrexed. However, a large scale clinical trial is required to validate these findings.