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Algal toxins are secondary metabolites produced by harmful algae; these metabolites are characterized with strong toxicity, diverse structure and bioaccumulation. Aquatic organisms that feed on harmful algae can accumulate algal toxins in their bodies, and the consumption of these organisms by humans can cause symptoms of paralysis, diarrhea, and even death. The onset of poisoning can occur within as little as 30 min; in many cases, no suitable antidote for algal toxins is available. Thus, algal toxins present significant threats to human health, the aquaculture industry, and aquatic ecosystems. Because the potential risks of algal toxins are a critical issue, these toxins have become a research hotspot. The water environment and various types of aquatic products should be monitored and analyzed to ensure their safety. However, because of possible matrix effects and the low content of algal toxins in actual samples, an efficient pretreatment method is necessary prior to instrumental analyses. Efficient sample pretreatment techniques can not only reduce or eliminate interferences from the sample matrix during analysis but also enrich the target analytes to meet the detection limit of the analytical instrument, thereby ensuring the sensitivity and accuracy of the detection method. In recent years, sample pretreatment techniques such as solid-phase extraction (SPE), solid-phase microextraction (SPME), magnetic SPE (MSPE), dispersive SPE (DSPE), and pipette tip-based SPE (PT-SPE) have gained wide attention in the field of algal-toxin separation and analysis. The performance of these pretreatment techniques largely depends on the characteristics of the extraction materials. Given the diverse physicochemical properties of algal toxins, including their different molecular sizes, hydrophobicity/hydrophilicity, and charges, the design and preparation of materials suitable for algal-toxin extraction is an essential undertaking. The optimal extraction material should be capable of reversible algal-toxin adsorption and preferably possess a porous structure with a large surface area to allow for high recovery rates and good interfacial contact with the toxins. Additionally, the extraction material should exhibit good chemical stability in the sample solution and elution solvent within the working pH range; otherwise, it may dissolve or lose its functional groups. Many research efforts have sought to develop novel adsorbent materials with these properties in the separation and analysis of algal toxins, focusing on carbon-based materials, metal organic frameworks (MOFs), covalent organic frameworks (COFs), molecularly imprinted polymers (MIPs), and their functionalized counterparts. Carbon-based materials, MOFs, and COFs have advantages such as large surface areas and abundant adsorption sites. These extraction materials are widely used in the separation and analysis of target substances in complex environmental, biological, and food samples owing to their excellent performance and unique microstructure. They are also the main adsorbents used for the extraction of algal toxins. These extraction materials play an essential role in the extraction of algal toxins, but they also present a number of limitations: (1) Carbon-based materials, MOFs, and COFs have relatively poor selective-adsorption ability towards target substances; (2) Most MOFs are unstable in aqueous solutions and challenging to apply during extraction from water-based sample solutions; (3) COFs mainly consist of lightweight elements, rendering them difficult to completely separate from sample solutions using centrifugal force, which limits their application range; (4) Although MIPs have good selectivity, issues such as template-molecule loss, slow mass-transfer rates, and low adsorption capacity must be addressed. Therefore, the design and preparation of novel functionalized extraction materials specifically tailored for algal toxins and studies on new composite extraction materials are highly desirable. This article collects representative literature from domestic and international research on algal-toxin analysis over the past decade, summarizes the relevant findings, categorizes the applications of novel functional materials in algal-toxin-extraction processes, and provides an outlook on their future development prospects.

Algal toxins are important metabolites of toxic harmful algal blooms (HABs), and their qualitative and qualitative detection can serve as early warning indicators for toxic HABs, complementing traditional HAB monitoring and improving the accuracy of early warning. Therefore, this work took the detection of domoic acid (DA) as an example and prepared zeolitic imidazolate framework-8 (ZIF-8) with high enrichment performance and high water stability and its core-shell composite material SiO 2 @ZIF-8 as an adsorbent filler. Density functional theory (DFT) calculations and interference experiments verified that Zn 2+ on SiO 2 @ZIF-8 played a crucial role in enriching DA on SiO 2 @ZIF-8. By using it as a solid-phase extraction (SPE) filler, it showed excellent performance compared with other SPE columns (C18/HLB/SAX/ZIF-8). Therefore, the SiO 2 @ZIF-8 column was coupled to high-performance liquid chromatography-mass spectrometry (SPE-HPLC-MS/MS) to establish a highly sensitive detection method for algal toxins in seawater, which had a wide linear range (12.0-5000.0 ng L -1 ), good reproducibility (RSD) and low limit of detection (4.0 ng L -1 ), and realized the monitoring of trace DA in the Pingtan sea area of Fujian Province from 2021 to 2022. By comparing other HAB early warning indicators such as salinity and pH and combining them with the information released by the Fujian Provincial Ocean and Fisheries Bureau, the content of DA in seawater measured by the established SPE-HPLC-MS/MS method can provide reference information for HAB monitoring and early warning.

Objective: To evaluate the efficacy and safety of telbivudine treatment in pregnant patients with chronic hepatitis B to block mother-to-child transmission of hepatitis B virus (HBV)., Methods: Medline and the Chinese Biomedical Literature Database were searched for studies of HBV, mother-to-child transmission, and telbivudine. Of the 68 potentially relevant publications, eight randomized controlled trials (RCTs) conformed to the inclusion and exclusion criteria. Following data extraction, a meta-analysis was carried out with RevMan5.1 software., Results: Seven of the eight RCTs were in Chinese, and the remaining study was in English but carried out at a Chinese site. The RCTs comprised a total of 678 subjects, including 352 cases and 326 controls. Infants born to telbivudine-treated mothers had a significantly lower rate of HBsAg positivity and HBV DNA positivity at birth than the control group of infants (odds ratio (OR) = 0.27, 95% confidence interval (CI): 0.17, 0.43, P less than 0.00001; OR = 0.14, 95% CI: 0.06, 0.32, P less than 0.00001). Infants born to telbivudine-treated mothers also had significantly lower rates of mother-to-child transmitted HBV at 6 months (OR = 0.06, 95% CI: 0.02, 0.22, P less than 0.00001; OR = 0.05, 95% CI: 0.01, 0.25, P = 0.0003) and 12 months (OR = 0.13, 95% CI: 0.03, 0.56, P = 0.007; OR = 0.08, 95% CI: 0.02, 0.37, P = 0.001) after birth. The pre-telbivudine treatment levels of HBV DNA were not significantly different between pregnant women in the telbivudine-treated group and the control group (OR = 0.12, 95% CI: 0.00, 0.24, P = 0.04), but the HBV DNA levels were significantly lower in the telbivudine-treated group of pregnant women prior to delivery (OR = -3.92, 95% CI: -4.90, -2.95, P less than 0.00001). There was no evidence of telbivudine treatment being associated with more adverse side effects or complications during pregnancy or in the infant (OR = 1.72, 95% CI: 0.68, 4.38, P = 0.25; OR=0.69, 95% CI: 0.04, 11.24, P = 0.80)., Conclusion: Telbivudine treatment effectively and safely prevents mother-to-child transmission of HBV from chronically infected mothers with a high degree of infectivity late in pregnancy.

Background: Intravascular Brachytherapy as a tool to reduce restenosis is thought to alter vascular wall biology and vessel wall protein function. Platelet accumulation is also indeed important in the genesis of restenosis. We examine the in vitro effects of beta-radiation on the certain vessel wall extra cellular matrix proteins. We hypothesized that vessel wall (proteins) had become less prone to thrombosis., Methods: We examined platelet adhesion to 20-Gy beta radiation treated extra cellular matrix proteins under flow conditions. Platelet flow adhesion was evaluated or quantified by image analysis, aggregation size analysis using the Watershed program and real-time fluorescence images of thrombus formation. The effect of beta radiation on vWF was further showing by measuring the binding of domain-specific antibodies to radiation treated vWF., Results: 20-Gy beta radiation significantly decreased platelet adhesion to extra cellular matrix protein; vWF and collagen Type III and had no effect on the adhesion upon fibrinogen and fibronectin. The beta-radiation affected mostly the AI, A2 and A3 domains of the vWF molecule on the surface, whereas the D'-D3 and B-C1 domains on the surface remain unaffected and suggesting a significant decrease in vWF binding capacity to the GPIb, heparin and collagen ligands., Conclusion: Beta radiation treatment can alter the reactivity of the certain vessel wall extra cellular matrix proteins, in particular vWF and collagen. The vessel wall may become less prone to platelet adhesion, which results in decrease thrombus formation. It might help to reduce the onset of acute coronary occlusion after the intervention., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

A new improved flow system was developed to study the influence of blood flow pulsatility on platelet adhesion on adhesive proteins and bio-medical materials. The pulsatility was introduced by changing the shear rate every 15 s in blood that was aspirated through a perfusion chamber by a syringe pump. The advantage of this new system is that it avoids system related platelet activation. At steady low shear rate (300/s) after 5 min a collagen type III surface was covered for 24.2+/-3.8% with platelets. At steady high shear rate (1300/s) platelet coverage to collagen was 48.8+/-6.8%. When pulsatility was introduced by changing the shear rate was every 15 s form 300/s to 1300/s and vice-versa, platelet coverage after 5 min was increased to 60.4+/-4.0% (p<0.001). After 5 min perfusion samples were taken from the perfusate and the extent of platelet activation was measured. The significant difference in surface expression of P-selectin on platelets is only seen when comparing pulse flow with control (no flow). We concluded that a significant increase in platelet activation during blood pulsatile flow compared with steady flow, which results in an increased platelet adhesion to collagen.

Objective: To detect the presence of endothelial injury in patients with severe acute respiratory syndrome (SARS) via enhanced levels of tissue-type plasminogen activator (t-PA) and soluble thrombomodulin (sTM)., Methods: Case patients were from Xuanwu Hospital (Capital University of Medical Sciences, Beijing, China), and all of them met clinical criteria for SARS. Healthy controls were some of the hospital employees. Endothelial injury bio-markers tPA and sTM were detected by commercial ELISA-methods., Results: Classic plasma markers of endothelial injury, tPA and sTM significantly elevated in SARS patients in comparison to controls [t-PA: 1.48 +/- 0.16 nmol/L versus 0.25 +/- 0.03 nmol/L (P<0.0001), and sTM: 0.26 +/- 0.06 nmol/L versus 0.14 +/- 0.02 nmol/L (P<0.05)]. The only patient who died had extremely high levels of these endothelial injury markers (t-PA: 2.77 nmol/L and sTM: 1.01 nmol/L). The likelihood ratio analysis indicated the excellent discriminating power for SARS at the optimal cut-point of 0.49 nmol/L for tPA and 0.20 nmol/L for sTM, respectively. Significant numerical correlations were found among these endothelial injury markers in SARS patients. The numerical coefficient of correlation Pearson r between t-PA and sTM was 0.5867 (P<0.05)., Conclusion: Increased plasma concentrations of tPA and sTM in patients with SARS suggest the possibility of endothelial injury. SARS patients might need anticoagulant therapy or fibrinolytic therapy in order to reverse intraalveolar coagulation, microthrombi formation, alveolar and interstitial fibrin deposition. It may not only provide a useful treatment and prognostic index but also allow a further understanding of the pathological condition of the disease.

Amyloid fibrils are components of proteinaceous plaques that are associated with conformational diseases such as Alzheimer's disease, transmissible spongiform encephalopathies, and familial amyloidosis. Amyloid polypeptides share a specific quarternary structure element known as cross-beta structure. Commonly, fibrillar aggregates are modified by advanced glycation end products (AGE). In addition, AGE formation itself induces protein aggregation. Both amyloid proteins and protein-AGE adducts bind multiligand receptors, such as receptor for AGE, CD36, and scavenger receptors A and B type I, and the serine protease tissue-type plasminogen activator (tPA). Based on these observations, we hypothesized that glycation induces refolding of globular proteins, accompanied by formation of cross-beta structure. Using transmission electron microscopy, we demonstrate here that glycated albumin condensates into fibrous or amorphous aggregates. These aggregates bind to amyloid-specific dyes Congo red and thioflavin T and to tPA. In contrast to globular albumin, glycated albumin contains amino acid residues in beta-sheet conformation, as measured with circular dichroism spectropolarimetry. Moreover, it displays cross-beta structure, as determined with x-ray fiber diffraction. We conclude that glycation induces refolding of initially globular albumin into amyloid fibrils comprising cross-beta structure. This would explain how glycated ligands and amyloid ligands can bind to the same multiligand "cross-beta structure" receptors and to tPA.

Liver cancer and liver cirrhosis are common causes of death in China, where chronic lifelong hepatitis B infection is a major cause of both diseases. To help determine whether smoking is a cofactor for the development of liver cancer, we ascertained retrospectively the smoking habits of 36,000 adults who had died from liver cancer (cases) and 17,000 who had died from cirrhosis (controls) in 24 Chinese cities and 74 rural counties. Calculations of the smoker vs. nonsmoker risk ratios (RR) for liver cancer mortality were standardised for age and locality. Among adult men (aged 35+) there was a 36% excess risk of death from liver cancer among smokers (smoker vs. nonsmoker standardised risk ratio [RR] =1.36, with 95% confidence interval [CI] 1.29-1.43, 2p<0.00001; attributable fraction 18%). In the general male population this indicates absolute risks of death from liver cancer before age 70 of about 4% in smokers and 3% in nonsmokers (in the absence of other causes). Most liver cancer, however, occurs among the 10-12% of men with haematological evidence of chronic hepatitis B infection, so among them the corresponding risks would be about 33% in smokers and 25% in nonsmokers. The RR was approximately independent of age, was similar in urban and rural areas, was not significantly related to the age when smoking started but was significantly (p<0.001) greater for cigarette smokers than for smokers of other forms of tobacco. Among men who smoked only cigarettes, the RR was significantly (p<0.001 for trend) related to daily consumption, with a greater hazard among those who smoked 20/day (RR 1.50, 95% CI 1.39-1.62) than among those who smoked fewer (mean 10/day: RR=1.32, 95% CI 1.23-1.41). Smoking was also associated with a significant excess of liver cancer death in women (RR 1.17, 95% CI 1.06-1.29, 2p=0.003; attributable fraction 3%), but fewer women (17%) than men (62%) were smokers, and their cigarette consumption per smoker was lower. Among women who smoked only cigarettes, there was a significantly greater hazard among those who smoked at least 20/day (mean 22/day: RR=1.45, 95% CI 1.18-1.79) than among those who smoked fewer (mean 8/day: RR=1.09, 95% CI 0.94-1.25). These associations indicate that tobacco is currently responsible for about 50,000 liver cancer deaths each year in China, chiefly among men with chronic HBV infection., (Copyright 2003 Wiley-Liss, Inc.)

Objective: DNAzyme/Deoxyribozyme is another novel molecular biological tool following the ribozyme. DNAzyme consists of a 15-nucleotide (nt) internal loop as its catalytic domain and two flanking substrate-recognition domains of 7 to 8 nt each which is complementary to substrate. The RNA substrate is cleaved at a particular phosphodiester located between an unpaired purine and a paired pyrimidine residue. DNAzyme has been applied in fields such as viral infectious disease, tumor, cardiovascular disease and genetic disease. But there is no report about using DNAzyme for anti-respiratory syncytial virus purpose. To observe the inhibitory effects of RNA-cleaving DNAzymes on respiratory syncytial virus (RSV) replication in cultured cells., Methods: Anti-RSV RNA-cleaving DNAzyme DZ604 was designed to target the RSV genome at the start of the NS2 gene in an effort to inhibit the RNA replication. Microscope and electron microscope were used to observe the effects of anti-RSV genomic RNA DNAzyme on cytopathogenic effect (CPE) and ultrastructural change of 9HTE cell induced by RSV infection. Viral plaque forming reduction assay and MTT assay were used to detect the anti-RSV activity and protective function for RSV infected 9HTE cells of DNAzyme., Results: Anti-RSV genomic RNA DNAzyme (DZ604) significantly improved CPE of RSV-infected 9HTE cells. The time to appearance of CPE and of total CPE was delayed by using DZ604 in a dose-dependent manner. At a 5 micro mol/L concentration of DZ604, CPE of 9HTE cells induced by RSV infection at 10 and 1 multiplicity of infection (MOI) was not improved. At smaller MOI (0.1, 0.01, 0.001, 0.0001) of RSV infection, CPE of 9HTE cells was significantly lightened by DZ604 at the same concentration. DZ604 also significantly improved ultrastructural change of 9HTE cells at early stage of RSV infection. Reduction in RSV yield was 85.56% and 8.33% at concentrations of 5 micro mol/L and 0.25 micro mol/L of DZ604. DZ604 inhibited RSV yield in a dose-dependent manner (P < 0.05). Non-specific DNAzyme did not have anti-RSV activity (P > 0.05)., Conclusion: Anti-RSV genomic RNA DNAzyme designed and synthesized in our laboratory was capable of inhibiting respiratory syncytial virus replication specifically in cultured cells. Our data indicated that DNAzymes could be useful for the prevention against respiratory syncytial virus infection.

Tissue-type plasminogen activator (tPA) regulates fibrin clot lysis by stimulating the conversion of plasminogen into the active protease plasmin. Fibrin is required for efficient tPA-mediated plasmin generation and thereby stimulates its own proteolysis. Several fibrin regions can bind to tPA, but the structural basis for this interaction is unknown. Amyloid beta (Abeta) is a peptide aggregate that is associated with neurotoxicity in brains afflicted with Alzheimer's disease. Like fibrin, it stimulates tPA-mediated plasmin formation. Intermolecular stacking of peptide backbones in beta sheet conformation underlies cross-beta structure in amyloid peptides. We show here that fibrin-derived peptides adopt cross-beta structure and form amyloid fibers. This correlates with tPA binding and stimulation of tPA-mediated plasminogen activation. Prototype amyloid peptides, including Abeta and islet amyloid polypeptide (IAPP) (associated with pancreatic beta cell toxicity in type II diabetes), have no sequence similarity to the fibrin peptides but also bind to tPA and can substitute for fibrin in plasminogen activation by tPA. Moreover, the induction of cross-beta structure in an otherwise globular protein (endostatin) endows it with tPA-activating potential. Our results classify tPA as a multiligand receptor and show that cross-beta structure is the common denominator in tPA binding ligands.

In this research, we found CoMFA alone could not obtain sufficiently a strong equation to allow confident prediction for aminobenzenes. When some other parameter, such as heat of molecular formation of the compounds, was introduced into the CoMFA model, the results were improved greatly. It gives us a hint that a better description for molecular structures will yield a better prediction model, and this hint challenged us to look for another method--the projection areas of molecules in 3D space for 3D-QSAR. It is surprising that much better results than that obtained by using CoMFA were achieved. Besides the CoMFA analysis, multiregression analysis and neural network methods for building the models were used in this paper.

ADP plays a central role in regulating platelet function. It induces platelet aggregation via the activation of 2 major ADP receptors, P2Y(1) and P2Y(12). We have investigated the role of P2Y(12) in platelet adhesion and thrombus formation under physiological flow by using blood from a patient with a defect in the gene encoding P2Y(12). Anticoagulated blood from the patient and from healthy volunteers was perfused over collagen-coated coverslips. The patient's thrombi were smaller and consisted of spread platelets overlying platelets that were not spread, whereas control thrombi were large and densely packed. Identical platelet surface coverage, aggregate size, and morphology were found when a P2Y(12) antagonist, N(6)-(2-methylthioethyl)-2-(3,3,3-trifluoropropylthio)-beta,gamma-dichloromethylene ATP (also known as AR-C69931 MX), was added to control blood. The addition of a P2Y(1) antagonist (adenosine-3',5'-diphospate) to control blood resulted in small, but normally structured, thrombi. Thus, the ADP-P2Y(12) interaction is essential for normal thrombus buildup on collagen. The patient's blood also showed reduced platelet adhesion on fibrinogen, which was not due to changes in morphology. Comparable results were found by using control blood with AR-C69931 MX and also with adenosine-3',5'-diphospate. This suggested that P2Y(12) and P2Y(1) were both involved in platelet adhesion on immobilized fibrinogen, thereby revealing it as ADP dependent. This was confirmed by complete inhibition on the addition of creatine phosphate/creatine phosphokinase.