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Brevetoxins (PbTxs) are very potent marine neurotoxins that can cause an illness clinically described as neurologic shellfish poisoning (NSP). These toxins are cyclic polyether in chemistry and have increased their geographical distribution in the past 2 decades. However, the ethical problems as well as technical difficulties associated with currently employed analysis methods for marine toxins have spurred the quest for suitable alternatives to be applied in a regulatory monitoring regime. In this work, we reported the first instance of concurrent aptamer selection of Brevetoxin-1 (PbTx-1) and Brevetoxin-2 (PbTx-2) and constructed a biolayer interferometry (BLI) biosensor utilizing PbTx-1 aptamer as a specific recognition element. Through an in vitro selection process, we have, for the first time, successfully selected DNA aptamers with high affinity and specificity to PbTx-1 and PbTx-2 from a vast pool of random sequences. Among the selected aptamers, aptamer A5 exhibited the strongest binding affinity to PbTx-1, with an equilibrium dissociation constant (KD) of 2.56 μM. Subsequently, we optimized aptamer A5 by truncation to obtain the core sequence (A5-S3). Further refinement was achieved through mutations based on the predictions of a QGRS mapper, resulting in aptamer A5-S3G, which showed a significant increase in the KD value by approximately 100-fold. Utilizing aptamer A5-S3G, we fabricated a label-free, real-time optical BLI aptasensor for the detection of PbTx-1. This aptasensor displayed a broad detection range from 100 nM to 4000 nM PbTx-1, with a linear range between 100 nM and 2000 nM, and a limit of detection (LOD) as low as 4.5 nM. Importantly, the aptasensor showed no cross-reactivity to PbTx-2 or other marine toxins, indicating a high level of specificity for PbTx-1. Moreover, the aptasensor exhibited excellent reproducibility and stability when applied for the detection of PbTx-1 in spiked shellfish samples. We strongly believe that this innovative aptasensor offers a promising alternative to traditional immunological methods for the specific and reliable detection of PbTx-1.

Clavatols exhibit a wide range of biological activities due to their diverse structures. A genome mining strategy identified an A5cla cluster from Penicillium sp. MYA5, derived from the Arctic plant Dryas octopetala, is responsible for clavatol biosynthesis. Seven clavatols, including one new clavatol derivate named penicophenone F (1) and six known clavatols (2–7), were isolated from Penicillium sp. MYA5 using a transcriptome mining strategy. These structures were elucidated by comprehensive spectroscopic analysis. Antibacterial, aldose reductase inhibition, and siderophore-producing ability assays were conducted on compounds 1–7. Compounds 1 and 2 demonstrated inhibitory effects on the ALR2 enzyme with inhibition rates of 75.3% and 71.6% at a concentration of 10 μM, respectively. Compound 6 exhibited antibacterial activity against Staphylococcus aureus and Escherichia coli with MIC values of 4.0 μg/mL and 4.0 μg/mL, respectively. Additionally, compounds 1, 5, and 6 also showed potential iron-binding ability.

Eight new 12,8-eudesmanolide sesquiterpenes, eutypellaolides A–H (1–8), and two new eudesmane-type sesquiterpenes, eutypellaolides I–J (9–10), along with four known 12,8-eudesmanolide compounds 11–14, were isolated from the culture extract of the polar fungus Eutypella sp. D-1 by one strain many compounds (OSMAC) approach. The structures of these compounds were determined through comprehensive spectroscopic data and experimental and calculated ECD analysis. Antibacterial, immunosuppressive, and PTP1B inhibition activities of these compounds were evaluated. Compounds 1 and 11 exhibited strong inhibitory activities against Bacillus subtilis and Staphylococcus aureus, with each showing an MIC value of 2 μg/mL. Compound 9 displayed weak immunosuppressive activity against ConA-induced T-cell proliferation with an inhibitory rate of 61.7% at a concentration of 19.8 μM. Compounds 5, 11, and 14 exhibited weak PTP1B inhibition activities with IC50 values of 44.8, 43.2, and 49.5 μM, respectively.

ObjectivesThis study was performed to investigate the changes and influencing factors of liver controlled attenuation parameter (CAP) in obese patients with polycystic ovary syndrome (PCOS), and to determine the prevalence and risk factors of nonalcoholic fatty liver disease (NAFLD) in PCOS patients with obesity.MethodsForty-one PCOS patients with obesity and twenty age- and body mass index (BMI)-matched control women without PCOS were enrolled in this study. General data, body composition, biochemical parameters, sex hormones, and liver CAP in the two groups were collected and compared. Liver CAP was measured using transient elastography.ResultsNAFLD was more common in the Obese PCOS group than in the control group (75.61% vs. 45.00%, P=0.018). Compared to the control group, the obese PCOS group showed apparent increases in alanine transaminase (ALT), aspartate transaminase (AST), CAP, triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), totle testosterone (TT), free androgen index (FAI), fasting insulin (FIns), and homeostasis model assessment-insulin resistance (HOMA-IR), along with lower high-density lipoprotein cholesterol (HDL-C) and sex hormone binding globulin (SHBG) levels. In addition, as shown by Spearman analysis, liver CAP in PCOS patients with obesity had a positive correlation with ALT, AST, TG, TT, FAI, FIns, and HOMA-IR, and a negative correlation with SHBG. Logistic regression analysis showed that TG, TT, FIns, and HOMA-IR were risk factors for NAFLD, while TT was an independent risk factor for NAFLD in PCOS patients with obesity.ConclusionPCOS patients with obesity had a significantly higher prevalence of NAFLD. Furthermore, in PCOS patients with obesity, liver CAP was associated with disorders of lipid metabolism, insulin resistance, and hyperandrogenemia, with elevated testosterone levels being an independent risk factor for NAFLD in PCOS patients with obesity.

In addition to the light curve and energy spectrum, polarization is also important for inferring the physical properties of the gamma-ray burst (GRB). Rotation of the polarization angle (PA) with time will cause depolarization of the time-integrated polarization degree. However, it has rarely been studied before. Here, we use a magnetic reconnection model with a large-scale ordered aligned magnetic field in the emitting region to study the influence of the parameters on the PA rotations in the GRB prompt phase. We find that the half-opening angle of the jet θ _j , the observational angle θ _V , and the bulk Lorentz factor Γ all have significant impacts on the PA rotations. The PA rotations are affected by the product value of θ _j Γ _0 (Γ _0 is the normalization factor of Γ with ${\rm{\Gamma }}{(r)={{\rm{\Gamma }}}_{0}(r/{r}_{0})}^{s}$ ), but are roughly independent of the concrete values of both θ _j and Γ _0 . For the typical parameters, the changes of the PA within T _90 (△PA) would be within (12°, 66°) for slight off-axis observations, where T _90 is the duration of the burst with the accumulated flux density ranging from 5% to 95%. The q range for △PA > 10° becomes smaller with the increase of the product value of θ _j Γ _0 . The most significant PA rotation with △PA ∼ 90° will happen when θ _j Γ _0 > 50 and 1.0 < q ≤ 1.2.

The time-integrated polarization degree (PD) in the prompt optical band of a gamma-ray burst (GRB) was predicted to be less than 20%, while the time-resolved one can reach as high as 75% in the photosphere model. Polarizations in the optical band during the GRB prompt phase have not previously been studied in the framework of the magnetic reconnection model. Here, a three-segment power law of the energy spectrum is used to reconstruct the Stokes parameters of the magnetic reconnection model. Multiwavelength light curves and polarization curves from the optical band to MeV gamma rays in the GRB prompt phase are studied. We found that, depending mainly on the jet dynamics, there is a long-lasting high-PD phase in all calculated energy bands for the typical parameter sets. The time-resolved PD could be as high as 50%, while the time-integrated one is roughly 17% in the optical band. The time-resolved PD in X-rays can reach 60% and the time-integrated one is around 30%–40%. The evolution of polarization angle (PA) is random in both optical and gamma-ray bands for the photosphere model, while it is roughly constant in the synchrotron models. Therefore, future time-resolved PA observations in the prompt optical or gamma-ray band could distinguish between the photosphere and synchrotron models.

Eight new scalarane sesterterpenes, phyllofenones F–M (1–8), together with two known analogues, carteriofenones B and A (9–10), were isolated from the marine sponge Phyllospongia foliascens collected from the South China Sea. The structures of these compounds were determined based on extensive spectroscopic and quantum chemical calculation analysis. The antibacterial and cytotoxic activity of these compounds was evaluated. Among them, only compounds 4 and 6 displayed weak inhibitory activity against Staphylococcus aureus and Escherichia coli, with MIC values of 16 μg/mL and 8 μg/mL, respectively. Compounds 1–10 exhibited cytotoxic activity against the HeLa, HCT-116, H460, and SW1990 cancer cell lines, with IC50 values ranging from 3.4 to 19.8 μM.

Non-alcoholic fatty liver disease (NAFLD) has become one of the important causes of cirrhosis and liver cancer, resulting in a huge medical burden worldwide. Currently, effective non-invasive diagnostic indicators and drugs for NAFLD are still lacking. With the development of metabolomics technology, the changes in metabolites during the development of NAFLD have been gradually revealed. Bile acid (BA) is the main endpoint of cholesterol metabolism in the body. In addition, it also acts as a signaling factor to regulate metabolism and inflammation in the body through the farnesyl X receptor and G protein-coupled BA receptor. Studies have shown that BA metabolism is associated with the development of NAFLD, but a large number of animal and clinical studies are still needed. BA homeostasis is maintained through multiple negative feedback loops and the enterohepatic circulation of BA. Recently, treatment of NAFLD by interfering with BA synthesis and metabolism has become a new research direction. Here, we review the changes in BA metabolism and its regulatory mechanisms during the development of NAFLD and describe the potential of studies exploring novel non-invasive diagnostic indicators and therapeutic targets for NAFLD based on BA metabolism.

A chemical investigation of the Arctic-derived fungus Eutypella sp. D-1 based on the OSMAC (one strain many compounds) approach resulted in the isolation of five cytosporin polyketides (compounds 1–3 and 11–12) from rice medium and eight cytosporins (compounds 2 and 4–11) from solid defined medium. The structures of the seven new compounds, eutypelleudesmane A (1), cytosporin Y (2), cytosporin Z (3), cytosporin Y1 (4), cytosporin Y2 (5), cytosporin Y3 (6), and cytosporin E1 (7), were elucidated by analyzing their detailed spectroscopic data. Structurally, cytosporin Y1 (4) may be a key intermediate in the biosynthesis of the isolated cytosporins, rather than an end product. Compound 1 contained a unique skeleton formed by the ester linkage of two moieties, cytosporin F (12) and the eudesmane-type sesquiterpene dihydroalanto glycol. Additionally, the occurrence of cyclic carbonate moieties in compounds 6 and 7 was found to be rare in nature. The antibacterial, immunosuppressive, and cytotoxic activities of all compounds derived from Eutypella sp. D-1 were evaluated. Unfortunately, only compounds 3, 6, 8, and 10–11 displayed immunosuppressive activity, with inhibitory rates of 62.9%, 59.5%, 67.8%, 55.8%, and 68.7%, respectively, at a concentration of 5 μg/mL.

We conducted a comparative analysis to unveil the divergence among venoms from a subset of Old World habu snakes (Protobothrops) in terms of venomic profiles and toxicological and enzymatic activities. A total of 14 protein families were identified in the venoms from these habu snakes, and 11 of them were shared among these venoms. The venoms of five adult habu snakes were overwhelmingly dominated by SVMP (32.56 ± 13.94%), PLA2 (22.93 ± 9.26%), and SVSP (16.27 ± 4.79%), with a total abundance of over 65%, while the subadult P. mangshanensis had an extremely low abundance of PLA2 (1.23%) but a high abundance of CTL (51.47%), followed by SVMP (22.06%) and SVSP (10.90%). Apparent interspecific variations in lethality and enzymatic activities were also explored in habu snake venoms, but no variations in myotoxicity were found. Except for SVSP, the resemblance of the relatives within Protobothrops in other venom traits was estimated to deviate from Brownian motion evolution based on phylogenetic signals. A comparative analysis further validated that the degree of covariation between phylogeny and venom variation is evolutionarily labile and varies among clades of closely related snakes. Our findings indicate a high level of interspecific variation in the venom proteomes of habu snakes, both in the presence or absence and the relative abundance of venom protein families, and that these venoms might have evolved under a combination of adaptive and neutral mechanisms.

Most of the constitutive model for liquefaction analysis cannot simulate the large post-liquefaction deformation of saturated sand, and there is little research on the nonlinear time-domain large deformation constitutive relationships suitable for seismic response analysis of saturated sand sites. In this paper, a feasible, simple and applicable large deformation constitutive model for time domain analysis is proposed through experimental analysis and theoretical research. The post-liquefaction stress-strain relationships of liquefied sand are obtained based on the undrained cyclic triaxial test data, then loading-reloading rules of large post-liquefaction deformation are proposed. Combined with the effective stress constitutive model based on logarithmic skeleton curve, a constitutive model that can quantitatively describe the large deformation of saturated sand liquefaction is proposed. According to the test results, the constitutive model can simulate small to large deformations from the pre-to post-liquefaction regime of sand. This constitutive model is also implemented to the program Soilresp1D for the dynamic response analysis of liquefiable soil sites. The results show that the time domain nonlinear large deformation unified constitutive model based on the logarithmic dynamic skeleton curve, effective stress-modified logarithmic dynamic skeleton constitutive model and liquefaction large deformation constitutive model can be directly applied to the dynamic response analysis of saturated sand.

The MAX phase of the ternary layered compound and the recently attracted attention of the MAB phase have become the research hotspots in the field of structural ceramics for more than 20 years because of their common characteristics of ceramics and metals. The high damage tolerance and high fracture toughness are different from the essential characteristics of traditional ceramics. The overall development of MAX phase and the latest research progress of MAB phase were briefly reviewed in this article, focusing on the analysis of the effect of multi-scale layered structure on macro-mechanical behavior and its internal mechanism. Based on the results of first-principles calculations,the bond stiffness model was established and the quantitative characterization of chemical bond strength was realized, and more importantly, it was clarified that "sufficiently" weak interlayer bonding is the root cause for the extraordinary mechanical properties of ternary layered ceramics. The magnetocaloric effect (MCE) of Fe2AlB2 near room temperature shows the good application prospects of MAB phase compounds in the functional field. After more than 20 years of continuous research, the structure and performance of MAX-phase compounds have gradually become clear. At present, application research for specific scenarios is vigorously carried out all over the world. However, the current knowledge of MAB phase compounds is still very limited. Therefore, synthesizing and characterizing the structure, mechanical properties, physical properties, and service behaviour of existing MAB phase compounds are the important tasks at this stage. First-principles numerical simulation based on density functional theory (DFT) can play an important role, just as in understanding the extraordinary properties of MAX phase compounds and discovering new compounds.

Benign recurrent intrahepatic cholestasis (BRIC) is an autosomal recessive disorder characterized by recurrent cholestasis. ATPase class I, type 8B, member 1 (ATP8B1) encodes familial intrahepatic cholestasis 1 (FIC1), which acts as a phosphatidylserine reversing enzyme in the tubule membrane of hepatocytes to mediate the inward translocation of phosphatidylserine (PS). At present, dozens of ATP8B1 pathogenic mutations have been identified that mainly cause BRIC1 and progressive familial intrahepatic cholestasis 1 (PFIC1). The diagnosis of BRIC1 is based on symptoms, laboratory tests, imaging, liver histology, and genetic testing. BRIC1 treatment seeks to prevent recurrence and reduce disease severity. At present, the main treatment methods include ursodeoxycholic acid (UDCA), rifampin, cholestyramine and haemofiltration, and endoscopic nasobiliary drainage (ENBD). Here, we report a 17-year-old patient with cholestasis who has a rare heterozygous ATP8B1 gene mutation (p.T888K). The patient was treated with UDCA, glucocorticoids and haemofiltration, after which bilirubin levels gradually returned to normal. This case was thought to be caused by an ATP8B1 heterozygous mutation, which may be related to haploinsufficiency (HI).

Objective To investigate the characteristics of clinical treatment and prognosis of 118 cases of retinoblastoma (RB). Methods A total of 118 RB children treated in our department from February 2008 to February 2018 were recruited in this study. All of them were evaluated by the International Classification for Intraocular Retinoblastoma (IIRC, A~E stage) and extraocular staging standard. Mainly according to their tumor stage, combined with their physical condition and the wishes of their parents, treatments such as intravenous chemotherapy, transpupillary thermotherapy (TTT), freezing and enucleation were applied. All cases were followed up for 1 to 10 years, and the clinical efficacy and prognosis of the patients were analyzed retrospectively. Results The 118 enrolled children (154 eyes) were 70 males and 48 females, at an average age of 25.94±20.88 months (1~122 months) at first visit, and 36 of them suffered from bilateral RB and 82 from single. Among them, 41 received chemotherapy, 57 chemotherapy combined with TTT, 10 chemotherapy combined with freezing, and 10 enucleation only. After treatment, 76 eyes (76/154) were salvaged, with a total salvage rate of 49.35%, and of them, 47 eyes were treated with chemotherapy combined with TTT, accounting for 61.84% (47/76). Seventy-eight eyes were enucleated, with a total extraction rate of 50.65% (78/154), and among 63 eyes at stage E, 53 were enucleated, accounting for 84.13%. During the mean follow-up time of 86.66±5.69 months, 22 (18.64%) children died, and 96 cases (81.36%) survived. The 5-year cumulative survival rate of single eye was 71.40%, and of bilateral was 80.00%. Conclusion Intravenous chemotherapy combined with TTT is one of the main ways for RB salvage. Enucleation is still the primary treatment for stage E eyes.

The rotations of the polarization angle (PA) with time (energy) can lead to the depolarization of the time-integrated (energy-integrated) polarization. However, we do not know how and when it will rotate. Here, we consider a magnetic reconnection model to investigate the polarizations, especially the PA rotations of gamma-ray burst (GRB) prompt emission. For a large-scale ordered aligned magnetic field configuration, we find that within T _50 PAs will rotate with time (energy) for slight off-axis observations. Our studies show that the rotations of the PAs are due to changes in the observed image of the emitting region before being averaged over the equal arrival time surface for the unresolved sources. We apply our model to the single-pulse bursts of GRB 170101A and GRB 170114A with time-resolved PA observations. We find it can interpret the violent PA variation of GRB 170101A, while the model could not predict the two 90° PA changes in GRB 170114A. A more detailed model should be considered.

Abstract Restoration has been promoted as an important strategy to reverse the decline of salt marsh ecosystems. Physical and biological processes limiting the colonization of bare tidal flats by pioneer salt marsh species are commonly recognized. Recently, the window of opportunity (WoO) concept has been proposed as a framework to provide an explanation for the initial establishment of biogeomorphic ecosystems on tidal flats under high physical stress. Understanding the thresholds for early seedling establishment and colonization is critical for the successful restoration and management of this threatened ecosystem. In this study, we investigated the WoOs for the establishment and colonization of a Scirpus mariqueter salt marsh at a large‐scale restoration site in the Yangtze Estuary. A set of field monitoring and measurements were conducted to identify the potential physical and biological thresholds that could provide a mechanistic insight on the establishment and colonization of this pioneer marsh. The results showed that the successful colonization and expansion of the S. mariqueter marsh on the tidal flat required passing both physical and biological thresholds to open WoOs for establishment and colonization. The concurrence of WoOs, that is, propagule availability in the early growing season at a suitable tidal flat elevation with a benign sedimentary regime together with the removal of competition from invasive species, is presumed to be essential for the success of S. mariqueter marsh establishment and colonization. In applying such ecological insights, the seed‐sowing field experiment proved that by surpassing these thresholds, an S. mariqueter salt marsh can be successfully restored in a cost‐effective manner. We suggest that these WoO‐related establishment and colonization thresholds as well the cost‐effectiveness of using these WoOs should be considered in future large‐scale restorations of salt marshes.

Abstract Background Echinococcosis is a serious, zoonotic, parasitic disease with worldwide distribution. According to a epidemiological survey in 2012 in China, there are 20,000 infected patients and more than 50 million people at the risk. As the dog is the main, definitive host, the Government of China encourages monthly praziquantel treatment of every dog. However, this is difficult to achieve in geographically challenging areas, such as the Tibetan plateau, where there are also many dogs without owners. To overcome these problems, we investigated the transmission blocking capacity of a slow-release formulation of praziquantel administered by subcutaneous injection. Methods The impact of a slow-release preparation of two pharmacokinetically stereoselective praziquantel enantiomers, i.e., R-(−)-praziquantel (R-PZQ) and S-(+)-praziquantel (S-PZQ) absorbed into a biodegradable polymer was studied in beagle dogs (N = 6). The preparation was given by subcutaneous injection using a single dose of 100 mg/kg. Chiral-selective, high-performance liquid chromatography (HPLC) and high-resolution mass spectrometry (HRMS) were applied to measure the praziquantel enantiomers in the plasma of the dogs. The lower limit for estimating plasma concentrations accurately for R-PZQ was 4 ng/ml and for S-PZQ 20 ng/ml. The pharmacokinetic parameters were calculated by a noncompartmental analysis model using Drug Analyze System (DAS) software 2.0. The SPSS 19.0 software was used for statistical analysis, and the statistical comparison between enantiomers was assessed using the two-tailed t-test. Results Two hours after administration, peak concentrations of R-PZQ and S-PZQ: 321 ± 26 and 719 ± 263 ng/ml, respectively, were achieved. After 180 days, the average plasma concentration of R-PZQ in the six dogs had decreased to 13 ng/ml. The average concentration value of S-PZQ was higher than that of R-PZQ in the first 90-day period but fell afterwards and could not be accurately estimated when dropping below 20 ng/ml (the lower methodological limit for this enantiomer). Taking all the dogs into account, the average maximum concentration (Cmax) of S-PZQ in plasma over the first 3 months was higher than that of R-PZQ by 114.0% (P

Chemical investigation on a marine sponge, Dactylospongia elegans, yielded five new γ-oxygenated butenolide sesterterpene derivatives, dactylospenes A–E (1–5), as well as two known biosynthetically related compounds, luffariellolide (6) and furospinosulin B (7). The structures of these compounds were elucidated on the basis of their spectroscopic data, experimental and calculated electronic circular dichroism (ECD) analysis, as well as comparison of the NMR data with those of known analogs. These metabolites are the first γ-oxygenated butenolide sesterterpenes to be reported from this genus. These compounds were evaluated in antimicrobial, anti-inflammatory, and cytotoxic assays. Only compounds 1, 3, and 6 exhibited moderate cytotoxicity against DU145, SW1990, Huh7, and PANC-1 cancer cell lines with IC50 values in the range of 2.11–13.35 μM. Furthermore, compound 2, without cytotoxicity, exhibited significant inhibitory effects (inhibitory rate 77.5%) on nitric oxide production induced by lipopolysaccharide at 10 μM.

Two new furan derivatives, hypofurans A and B (1 and 2), and three new cyclopentenone derivatives, hypocrenones A–C (3–5), along with seven known compounds (6–12), were isolated from a marine fungus Hypocrea koningii PF04 associated with the sponge Phakellia fusca. Among them, compounds 10 and 11 were obtained for the first time as natural products. The planar structures of compounds 1–5 were elucidated by analysis of their spectroscopic data. Meanwhile, the absolute configuration of 1 was determined as 2R,3R by the comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. All the isolates were evaluated for their antibacterial and antioxidant activity. Compounds 1, 10, and 12 all showed modest antibacterial activity against Staphylococcus aureus ATCC25923 (MIC, 32 μg/mL). In addition, compounds 1, 10 and 11 exhibited moderate DPPH radical scavenging capacity with IC50 values of 27.4, 16.8, and 61.7 µg/mL, respectively.

Abstract Background Cystic echinococcosis is a serious zoonotic infection worldwide caused by metacestodes of Echinococcus gruanulosus. Mebendazole and albendazole are the only two drugs used in the treatment of this disease with cure rates only about 30% due to the poor oral absorption. Thus an alternative treatment for this disease is needed. Methods A mebendazole oily suspension (MBZ-OS) was prepared and orally administrated to mice infected with echinococcus cysts for 8 months at 12.5 mg/kg and 25 mg/kg for 14 consecutive days. Mebendazole suspended in 1% tragacanth (MBZ-1% tragacanth) served as treated control. In addition, liver and serum samples were collected from these treated mice (25 mg/kg) for histopathology examination and liver function test. For pharmacokinetic analysis, plasma, parasite (cyst wall and cyst fluid) and tissue samples were collected at 0.25, 0.5, 1, 2, 4, 8, 16 and 24 h after orally administrating MBZ-OS and MBZ-1% tragacanth to E. granulosus-infected mice at 25 mg/kg. These samples were then processed and quantitatively analyzed by HPLC. Results The administration of MBZ-OS resulted in a treatment efficacy with the cyst weight reductions higher than 80%, significantly better than the corresponding MBZ-1% tragacanth groups. The better treatment efficacy of MBZ-OS was related to the higher drug concentration in plasma, parasites and tissues. It was also shown that the injury of the liver was not significantly altered by taking MBZ-OS compared to the untreated control. Conclusion These findings demonstrate that MBZ-OS is a promising new formulation of MBZ for treatment of hydatid diseases without showing significantly liver toxicity.

Five new alkaloids of aaptamine family, compounds (1–5) and three known derivatives (6–8), have been isolated from the South China Sea sponge Aaptos aaptos. The structures of all compounds were unambiguously elucidated by spectroscopic analyses, as well as by comparison with the literature data. Compounds 1–2 are characterized with triazapyrene lactam skeleton, whereas compounds 4–5 share an imidazole-fused aaptamine moiety. These compounds were evaluated in antifungal and anti-HIV-1 assays. Compounds 3, 7, and 8 showed antifungal activity against six fungi, with MIC values in the range of 4 to 64 μg/mL. Compounds 7–8 exhibited anti-HIV-1 activity, with inhibitory rates of 88.0% and 72.3%, respectively, at a concentration of 10 μM.

An unusual meroterpenoid, dysidinoid A (1), was isolated from the South China Sea sponge Dysidea sp. Its structure was elucidated by extensive spectroscopic methods including HRESIMS and 2D NMR, and its absolute configuration was determined by single-crystal X-ray diffraction analysis. Dysidinoid A (1) is the first meroterpenoid from Nature bearing a 9,4-friedodrime skeleton and a 2,5-dionepyrrole unit. Dysidinoid A (1) showed potent antibacterial activity against two strains of pathogenic bacteria methicillin-resistant Staphylococcus aureus (MRSA) with MIC90 values of 8.0 μg/mL against both.

Transgenic insect-resistant cotton is being increasingly planted in Xinjiang cotton-planting regions, where geographical climate conditions and species composition of pests and natural enemies are greatly unique in China. Limited studies have been conducted on the ecological impacts of transgenic insect-resistant cotton, especially for transgenic double genes (Bt+CpTI) cotton, in this region. In this study, the potential effects of transgenic Bt+CpTI cotton on the seasonal abundance of non-target pests and predators were assessed from 2009 to 2011 in Korla, Xinjiang. The results showed that species composition and seasonal abundance of 5 groups of pests and 5 groups of predators were not significantly different between transgenic Bt+CpTI cotton and non-transgenic cotton every year. It suggests that transgenic Bt+CpTI cotton per se does not affect the population dynamics of non-target pests and predators on this crop in Xinjiang.

Three new polyketides, woodylides A–C (1–3), were isolated from the ethanol extract of the South China Sea sponge Plakortis simplex. The structures were elucidated by spectroscopic data (IR, 1D and 2D NMR, and HRESIMS). The absolute configurations at C-3 of 1 and 3 were determined by the modified Mosher’s method. Antifungal, cytotoxic, and PTP1B inhibitory activities of these polyketides were evaluated. Compounds 1 and 3 showed antifungal activity against fungi Cryptococcus neoformans with IC50 values of 3.67 and 10.85 µg/mL, respectively. In the cytotoxicity test, compound 1 exhibited a moderate effect against the HeLa cell line with an IC50 value of 11.2 µg/mL, and compound 3 showed cytotoxic activity against the HCT-116 human colon tumor cell line and PTP1B inhibitory activity with IC50 values of 9.4 and 4.7 µg/mL, respectively.

A series of benzonaphthyridine derivatives bearing the C=N linkage moiety were designed and synthesized. The structures of all the newly synthesized compounds were identified by elemental analysis, 1H-NMR, 13C-NMR and MS. Their anti-intestinal nematode activities against Nippostrongylus brazilliensis were evaluated in vivo by an oral route in male rats. Among these compounds, at concentrations of 10 mg/kg of rat, the compound 7-chloro-2-methoxy-10-(4-(4′-(1H-indol-5′-yl)methylene)aminophenyl)-amino-benzo[b][1,5] naphthyridine (4n) produced the highest activity, with 80.2% deparasitization. These compounds may find usefulness in the discovery and development of new anti-intestinal drugs.

A series of 1-acyl-3-(2'-aminophenyl) thiourea derivatives were designed and synthesized. The structures of all the newly synthesized compounds were identified by IR, elemental analysis, 1H-NMR and 13C-NMR. Their anti-intestinal nematode activities against Nippostrongylus brazilliensis were evaluated in rats by an oral route. Among these compounds, at concentrations of 10 mg/kg of rat, compound (1-(2'-furanyl)acyl-3- (2'-aminophenyl) thiourea) (5h) produced the highest activity with 89.4% deparasitization. The present work suggests that 1-acyl-3-(2'-aminophenyl) thiourea derivatives may become useful lead compounds for anti-intestinal nematode treatment.

Three new pimarane diterpenes, eutypellenoids A–C (1–3), together with a known compound, eutypenoid C (4), were isolated from the culture extract of Eutypella sp. D-1 derived from the Arctic region. Compounds 1–3 possessed an uncommon tetrahydrofuran-fused pimarane diterpene skeleton. The structures of all compounds were determined by detailed spectroscopic analysis, electronic circular dichroism (ECD) analysis, as well as a comparison with the literature data. Antibacterial, antifungal, and cytotoxic activities of these compounds were evaluated. Compound 2 displayed antibacterial activity against Staphylococcus aureus and Escherichia coli with MIC values of 8 and 8 μg/mL, respectively. Additionally, compound 2 showed antifungal activity against Candida parapsilosis, Candida albicans, Candida glabrata, and Candida tropicalis with MIC values of 8, 8, 16, and 32 μg/mL, respectively. Furthermore, compound 2 exhibited moderate cytotoxic activity against HCT-116 cell line with IC50 value of 3.7 μM.

BackgroundBoth tribendimidine and mebendazole are broad-spectrum drugs for anti-intestinal nematodes. We aim to assess the efficacy and safety of tribendimidine and mebendazole in patients with co-infection of Clonorchis sinensis and other helminths.MethodWe performed a randomized open-label trial in Qiyang, People's Republic of China. Eligible participants were randomly assigned to one of four groups: (i) a single dose of 400 mg tribendimidine, (ii) 200 mg tribendimidine twice daily, (iii) 75 mg/kg praziquantel divided in four doses within 2 days, and (iv) a single dose of 400 mg mebendazole. Cure rates and egg reduction rates were assessed, and adverse events were monitored after treatments. Uncured patients accepted the second treatment with the same drugs after the first treatment.Results156 patients were eligible for the study. Results from the first treatment showed that the cure rates of single-dose tribendimidine and praziquantel against C. sinensis were 50% and 56.8%, respectively; the single-dose tribendimidine achieved the cure rate of 77.8% in the treatment for hookworm, which was significantly higher than that of praziquantel; Low cure rates were obtained in the treatment of single-dose tribendimidine against Ascaris lumbricoides and Trichuris trichiura (28.6% and 23.1%). Results of the second treatment illustrated the cure rates of tribendimidine and praziquantel against C. sinensis were 78.1% and 75%, respectively. Most adverse events were mild and transient. Adverse events caused by tribendimidine were significantly less than praziquantel.ConclusionSingle-dose tribendimidine showed similar efficacy against C. sinensis as praziquantel with less adverse events, and achieved significantly higher cure rate in the treatment for hookworm than those of praziquantel and mebendazole. Low cure rates, which were still higher than other drugs, were obtained in the treatment of single-dose tribendimidine against Ascaris lumbricoides and Trichuris trichiura.Trial registrationControlled-Trials.com ISRCTN55086560.

Coal resource is the main primary energy in our country, while Shanxi Province is the most important province in resource. Therefore Shanxi is an energy base for our country and has a great significance in energy strategy. However because of the heavy development of the coal resource, the ecological environment is worsening and the farmland is reducing continuously in Shanxi Province. How to resolve the contradiction between coal resource exploitation and environmental protection has become the imperative. Thus the concept of “green mining industry” is arousing more and more attention. In this assay, we will talk about the basic mode of land reclamation in mine area, the engineering study of mine land reclamation, the comprehensive model study of mine land reclamation, and the design and model of ecological agricultural reclamation in mining subsidence.

The initiating explosive devices are prohibited in rock breaking near the goaf of the highly gassy mine. It is effective and applicable to cracking the hard roof with static cracking agent. By testing the static cracking of cubic limestone (size: 200×200×200 mm) with true triaxial rock mechanics testing machine under the effect of bidirectional stress and by monitoring the evolution process of the cracks generated during the acoustic emission experiment of static cracking, we conclude the following: the experiment results of the acoustic emission show that the cracks start from the lower part of the hole wall until they spread all over the sample. The crack growth rate follows a trend of “from rapidness to slowness.” The expansion time is different for the two bunches of cracks. The growth rates can be divided into the rapid increasing period and the rapid declining period, of which the growth rate in declining period is less than that in the increasing period. Also, the growth rate along the vertical direction is greater than that of the horizontal direction. Then the extended model for the static cracking is built according to the theories of elastic mechanics and fracture mechanics. Thus the relation formula between the applied forces of cracks and crack expansion radius is obtained. By comparison with the test results, the model proves to be applicable. In accordance with the actual geological situation of Yangquan No. 3 Mine, the basic parameters of manpower manipulated caving breaking with static crushing are settled, which reaps bumper industrial effects.

C15H18N2O2, tetragonal, I41/a (no. 88), a = 14.662(1) Å, c = 26.049(2) Å, V = 5599.9 Å3, Z = 16, Rgt(F) = 0.0461, wRref(F2) = 0.1478, T = 298 K.

Abstract Background Hookworm is still one of the three main soil-transmitted helminths prevalent in China, and 39 million cases infected with hookworm were estimated in China in 2006. Results The main approach to the control of hookworm infections in China consists of large-scale deworming, rebuilding sanitation systems in rural areas and health education. The availability of low-cost, safe and single-dose albendazole make large-scale deworming programs possible in China. Currently, sanitary latrines with three-cells are recommended by government for the control of soil-transmitted helminths, since 35% of helminth infections and 83% of worm eggs could be reduced after using this kind of sanitary latrine. In addition, economic prosperity contributes greatly to the reduction of hookworm prevalence, but the inequity of economic and social development among different regions of China provides a scenario that the worst threat of hookworm infection is located in the poorest areas of southern and central China. Therefore, it is necessary to put more investments into prophylaxis and treatment of hookworm in these poor regions. Conclusion Although the prevalence of hookworm infection has fallen significantly in the last 15 years in China, the current strategy for controlling hookworm infections still needs to be strengthened along with the three-pronged approach, e.g. distributing anthelmintic drugs in schools and undertaking large-scale of hookworm deworming, improving water supplies and sanitation, and proper health education.