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Gastric cancer (GC) is one of the most prevalent malignancies with an unfavorable survival rate. Immunotherapy may contribute to a better prognosis. However, several phase III trials failed. Circular RNA (circRNA) is a novel type of non-coding RNA, plays a vital role in the progression of tumors. The expression and function of circRNA in the GC immune microenvironment remain obscure. In this study, we utilized a bioinformatic analysis to construct a circRNA/microRNA (miRNA)/messenger RNA (mRNA) network involved in the progression and prognosis of GC. CircRNA DYRK1A_017, circRNA FLNA_118, miR-6512-3p, miR-6270-5p, and VCAN were identified as the key molecules in the hub regulatory axis. Dysregulation of this axis contributed to the cancer-associated signaling pathways (epithelial-mesenchymal transition [EMT], Nuclear factor kappa β-Tumor necrosis factor-α (NFκβ-TNFα) signaling, and angiogenesis) and aberrant immune microenvironment (infiltration by tumor associated macrophage, regulatory T cell, and mast cell). More importantly, the immunosuppressive tumor microenvironment may reveal the mechanism of novel circRNAs in tumors and serve as the target of immunotherapy.

Antimalarial peroxides such as the phytochemical artemisinin or the synthetic ozonides arterolane and artefenomel undergo reductive cleavage of the pharmacophoric peroxide bond by ferrous heme, released by parasite hemoglobin digestion. The generated carbon-centered radicals alkylate heme in an intramolecular reaction and proteins in an intermolecular reaction. Here, we determine the proteinaceous alkylation signatures of artemisinin and synthetic ozonides in Plasmodium falciparum using alkyne click chemistry probes to identify target proteins by affinity purification and mass spectrometry-based proteomics. Using stringent controls and purification procedures, we identified 25 P. falciparum proteins that were alkylated by the antimalarial peroxides in a peroxide-dependent manner, but the alkylation patterns were more random than we had anticipated. Moreover, there was little overlap in the alkylation signatures identified in this work and those disclosed in previous studies. Our findings suggest that alkylation of parasite proteins by antimalarial peroxides is likely to be a nonspecific, stochastic process.

Rationale: Hedgehog (Hh) pathway plays an essential role in liver fibrosis by promoting the proliferation of hepatic stellate cells (HSCs) by enhancing their metabolism via yes-associated protein 1 (YAP1). Despite the presence of several inhibitors, Hh signaling cannot be controlled exclusively due to their poor efficacy and the lack of a suitable delivery system to the injury site. Therefore, it is rationale to develop new potent Hh inhibitors and suitable delivery carriers. Methods: Based on the structure and activity of Hh inhibitor GDC-0449, we replaced its sulfonamide group with two methylpyridine-2yl at amide nitrogen to synthesize MDB5. We compared the Hh pathway inhibition and anti-fibrotic effect of MDB5 with GDC-0449 in vitro. Next, we developed MDB5 loaded micelles using our methoxy poly(ethylene glycol)-blockpoly(2-methyl-2-carboxyl-propylene carbonate-graft-dodecanol (PEG-PCC-g-DC) copolymer and characterized for physicochemical properties. We evaluated the therapeutic efficacy of MDB5 loaded micelles in common bile duct ligation (CBDL) induced liver fibrosis, mouse model. We also determined the intrahepatic distribution of fluorescently labeled micelles after MDB5 treatment. Results: Our results show that MDB5 was more potent in inhibiting Hh pathway components and HSC proliferation in vitro. We successfully developed MDB5 loaded micelles with particle size of 40 ± 10 nm and drug loading up to 10% w/w. MDB5 loaded micelles at the dose of 10 mg/kg were well tolerated by mice, without visible sign of toxicity. The serum enzyme activities elevated by CBDL was significantly decreased by MDB5 loaded micelles compared to GDC-0449 loaded micelles. MDB5 loaded micelles further decreased collagen deposition, HSC activation, and Hh activity and its target genes in the liver. MDB5 loaded micelles also prevented liver sinusoidal endothelial capillarization (LSEC) and therefore restored perfusion between blood and liver cells. Conclusions: Our study provides evidence that MDB5 was more potent in inhibiting Hh pathway in HSC-T6 cells and showed better hepatoprotection in CBDL mice compared to GDC-0449.

The flow dynamics within and immediately above an artificial plastic vegetation canopy are measured in the field and wind tunnel. Artificial plants created from wooden dowels and cable (zip) ties were arranged in a variety of arrays on pegboards where plant cover (or lateral cover) could be accurately controlled. Plant covers examined ranged from ~12% to 60%. Wind velocity profiles and the bedforms (incipient dunes) that developed within and beyond the vegetation in a few hours were measured. The results indicate that flow deceleration and drag increases within the canopy as plant density increases. In general, there is a marked reduction and inflection in velocity at the canopy top, and a second major inflection in the velocity profiles occurs immediately below the base of the four arrays equal or >23% density. Tall vegetation allows flow to sweep under the canopy and local high speed maxima flows may develop leading to minimal sedimentation in those canopies, but deposition downwind beyond the canopies. Short vegetation, where the leaves fill the canopy close to the ground, display significantly greater drag and rapid rates of sand deposition. Flow velocities above the canopy increase as plant cover or density increases due to flow compression and acceleration. Bedform development is strongly correlated with plant cover, density or lateral cover and short plants such that shorter length, higher bedforms develop in higher density and/or shorter plants. The relationship between plant cover, density or lateral cover and within canopy velocity is non-linear, and a new tentative flow regime is proposed, canopy flow, which may occur between wake interference flow and skimming flow. This study further confirms that plant density plays a defining role in determining bedform and dune morphology. The results also apply to flow in semi-arid grasslands.

Castration-resistant prostate cancer that has become resistant to docetaxel (DTX) represents one of the greatest clinical challenges in the management of this malignancy. There is an urgent need to develop novel therapeutic agents to overcome chemoresistance and improve the overall survival of patients. We have designed a novel microtubule destabilizer (2-(4-hydroxy-1H-indol-3-yl)-1H-imidazol-4-yl)(3,4,5-trimethoxyphenyl)methanone (QW-296) and combined it with a newly synthesized hedgehog (Hh) signaling pathway inhibitor 2-chloro-N(1)-[4-chloro-3-(2-pyridinyl)phenyl]-N(4),N(4)- bis(2-pyridinylmethyl)-1,4-benzenedicarboxamide (MDB5) to treat taxane-resistant (TXR) prostate cancer. The combination of QW-296 and MDB5 exhibited stronger anticancer activity toward DU145-TXR and PC3-TXR cells and suppressed tumor colony formation when compared with single-drug treatment. Because these drugs are hydrophobic, we synthesized the mPEG-p(TMC-MBC) [methoxy-poly(ethylene glycol)-block-poly(trimethylene carbonate-co-2-methyl-2-benzoxycarbonyl-propylene carbonate)] copolymer, which could self-assemble into micelles with loading capacities of 8.13% ± 0.75% and 9.12% ± 0.69% for QW-296 and MDB5, respectively. Further, these micelles provided controlled the respective drug release of 58% and 42% release of QW-296 and MDB5 within 24 hours when dialyzed against PBS (pH 7.4). We established an orthotopic prostate tumor in nude mice using stably luciferase expressing PC3-TXR cells. There was maximum tumor growth inhibition in the group treated with the combination therapy of QW-296 and MDB5 in micelles compared with their monotherapies or combination therapy formulated in cosolvent. The overall findings suggest that combination therapy with QW-296 and MDB5 has great clinical potential to treat TXR prostate cancer, and copolymer mPEG-p(TMC-MBC) could serve as an effective delivery vehicle to boost therapeutic efficacy in vivo.

Carbon emissions research in rapidly urbanizing areas around the world has typically focused on numerical changes in regional carbon emissions, and less research has been conducted on the spatial and temporal characteristics of carbon emissions from different sources in the urban system. Here, based on Multi-Resolution Emission Inventory for China (MEIC) modeling data, carbon emissions from industrial, power generation, residential, and transportation sources were analyzed in the Pearl River Delta region from 2008 to 2012, and the corresponding spatiotemporal distributions and main influencing mechanisms were elucidated. The results were as follows. (1) From 2008 to 2012, the total amount of carbon emissions increased gradually, and carbon emissions per unit area increased from 6513.65 × 103 gC∙m−2∙a−1 to 7519.03 × 103 gC∙m−2∙a−1, where industrial carbon emissions were the highest, followed by power and transportation emissions; residential carbon emissions were the lowest. (2) The spatial characteristics of carbon emissions in the Pearl River Delta region showed a carbon emissions belt with a shape similar to that of the number seven and Shenzhen carbon emissions center. Industrial carbon emissions resembled a “one belt, one center” pattern. Power carbon emissions mainly showed a “seven shape” pertaining to a carbon emissions belt and secondary carbon emissions centers. Residential carbon emissions were mainly located in the Guangzhou–Foshan carbon emissions belt and Shenzhen secondary center. Lastly, transportation-related carbon emissions were mainly located in the Guangzhou–Foshan and Shenzhen–Dongguan carbon emissions belt. (3) From 2008 to 2012, carbon emissions from industrial, transportation, and residential sources all showed obvious spatial distribution characteristics related to the carbon belt of Guangzhou–Foshan, and the two carbon emissions centers displayed a centripetal agglomeration development trend, in which the emissions gradually expanded out from around this area. The reasons were attributed to the influences of the “Guangfo One City” policy, whereby joint development in Guangzhou and Foshan is being focused on in its entirety. (4) The future development direction of the Pearl River Delta region should be based on controlling the scale of urban development, construction of low-carbon industrial production areas, and low-carbon-oriented land use planning; the formulation of such reasonable measures would help to reduce future carbon emissions.

From the perspective of whole-area sponge city construction, it is important to scientifically determine the layout plan of LID facilities for controlling urban rainfall and flooding problems, given the topographical features and rainfall runoff characteristics of shallow urban mountainous areas. Current research on the optimization of low-impact development facilities is limited to the central urban area level, with insufficient research on shallow urban mountainous areas, and there is great uncertainty in the layout of LID facilities when multiple objectives are considered. Therefore, this paper applied a genetic algorithm (NSGA-II) to optimize the layout scheme of LID facilities. Multiple objectives of the peak runoff abatement rate, cost, and land area were selected as the optimization objectives, and the optimized results were ranked using the EWM-TOPSIS and VCWM-TOPSIS methods. The 2nd Hebei Provincial Garden Flower Expo (Qinhuangdao) Park was used as the research object for the optimization design. The results showed that, under the premise of water safety, the lowest cost priority was given to the LID facility with a 15.49% share, 99.43% peak runoff reduction rate, and a cost of CNY 1.215 × 107; the lowest area priority was given to the LID facility with a 15.25% share, 99.42% peak runoff reduction rate, and a cost of CNY 1.267 × 107. The EWM-TOPSIS method was also used to obtain the best optimized solution with 16.18% LID facilities, 99.64% peak runoff abatement rate, and a cost of CNY 1.26 × 107, and the worst optimized solution with 12.55% LID facilities, 97.91% peak runoff abatement rate, and a cost of CNY 1.061 × 107. The decision results under different decision-maker preferences were obtained by the VCWM-TOPSIS method. This study showed that the combination of a genetic algorithm and TOPSIS can optimize the layout of LID facilities in shallow mountainous areas more scientifically and efficiently compared to the actual construction plan for building a sponge city.

Collective memory plays a controlling role in adaptation to potential flood risks, by learning from past disasters. However, with little quantitative empirical data, previous socio‐hydrological models have conceptualized the decaying process of flood memory in an oversimple approach. Here, based on survey data of 683 respondents on Ningxia Floodplain, we confirmed that flood memory decays overtime via two channels: oral communication (communicative memory) and physical recording of information (cultural memory). Using the Universal Decay Model (UDM) proposed by previous researchers provides better fitting of results to the decay of flooding memory (adjusted R2 coefficient are 0.97, 0.90, 0.95 when data of all, rural or urban respondents used, respectively) compared with the original exponential model (adjusted R2 coefficient are 0.91, 0.74, 0.59, corresponding). Then, significantly reduced losses for the same flood sequence predicted by integrating the UDM into a socio‐hydrological model by 16% and the differences between different clusters (urban and rural respondents) can even reach 22.81%. These differences suggest that previous socio‐hydrological models have been too simplistic in their conceptualizations of decaying processes associated with collective memory, which may have limited deeper insights into flood risk management.

Abnormal tumor microenvironment (TME) not only facilitates tumor proliferation and metastasis, but also establishes physiological barriers for effective transport of therapeutics inside the tumor, posing great challenges for cancer treatment. Here we designed a core-satellite size transformable nanoframework (denoted as T-PFRT) that can synchronously adapt to and remold TME for augmenting photodynamic therapy to inhibit tumor growth and prevent tumor metastasis. Upon matrix metalloproteinase 2 (MMP2)-responsive dissociation of the nanoframework in TME, the core structure loaded with TGFβ signaling pathway inhibitor and oxygen-carrying hemoglobin aims to stroma remodeling and hypoxia relief, allowing the photosensitizer-encapsulated satellite particles to penetrate to deep-seated tumor for oxygen-fueled photodynamic therapy. We demonstrated that T-PFRT could overcome the stroma and hypoxia barriers for delivering therapeutics, and gain excellent therapeutic outcomes in the treatment of primary and metastatic tumors.

BackgroundCircular RNAs (circRNAs) are now under hot discussion as novel promising biomarkers for patients with hepatocellular carcinoma (HCC). The purpose of our study is to identify several competing endogenous RNA (ceRNA) networks related to the prognosis and progression of HCC and to further investigate the mechanism of their influence on tumor progression.MethodsFirst, we obtained gene expression data related to liver cancer from The Cancer Genome Atlas (TCGA) database (http://www.portal.gdc.cancer.gov/), including microRNA (miRNA) sequence, RNA sequence, and clinical information. A co-expression network was constructed through the Weighted Correlation Network Analysis (WGCNA) software package in R software. The differentially expressed messenger RNAs (DEmRNAs) in the key module were analyzed with the Database for Annotation Visualization and Integrated Discovery (DAVID) (https://david.ncifcrf.gov/summary.jsp) to perform functional enrichment analysis including Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). The data of miRNA expression and clinical information downloaded from TCGA were utilized for survival analysis to detach the prognostic value of the DEmiRNAs of the key module.ResultsThe 201 differentially expressed miRNAs (DEmiRNAs) and 3,783 DEmRNAs were preliminarily identified through differential expression analysis. The co-expression networks of DEmiRNAs and DEmRNAs were constructed with WGCNA. Further analysis confirmed four miRNAs in the most significant module (blue module) were associated with the overall survival (OS) of patients with liver cancer, including hsa-miR-92b-3p, hsa-miR-122-3p, hsa-miR-139-5p, and hsa-miR-7850-5p. DAVID was used for functional enrichment analysis of 286 co-expressed mRNAs. The GO analysis results showed that the top enriched GO terms were oxidation–reduction process, extracellular exosome, and iron ion binding. In KEGG pathway analysis, the top three enriched terms included metabolic pathways, fatty acid degradation, and valine, leucine, and isoleucine degradation. In addition, we intersected the miRNA–mRNA interaction prediction results with the differentially expressed and prognostic mRNAs. We found that hsa-miR-92b-3p can be related to CPEB3 and ACADL. By overlapping the data of predicted circRNAs by circBank and differentially expressed circRNAs of GSE94508, we screened has_circ_0077210 as the upstream regulatory molecule of hsa-miR-92b-3p. Hsa_circ_0077210/hsa-miR-92b-3p/cytoplasmic polyadenylation element binding protein-3 (CPEB3) and acyl-Coenzyme A dehydrogenase, long chain (ACADL) were validated in HCC tissue.ConclusionOur research provides a mechanistic elucidation of the unknown ceRNA regulatory network in HCC. Hsa_circ_0077210 might serve a momentous therapeutic role to restrain the occurrence and development of HCC.

Additional file 5: Figure S5. Correlation between 15 model immune genes and immune cell infiltration.

Additional file 4: Figure S4. Survival analysis of 15 model immune genes.

Additional file 3: Figure S3. Correlation analysis between TNM&Stage and 15 model genes in breast cancer cases. (A) Correlation analysis between tumor stage and 15 model genes expression in breast cancer cases. (B) Correlation analysis between node stage and 15 model genes expression in breast cancer cases. (C) Correlation analysis between metastasis stage and 15 model genes in breast cancer cases. (D) Correlation analysis between pathologic stage and 15 model genes expression in breast cancer cases.

At present, most of the international research cases on badlands are based on semiarid regions, while there are few studies on badlands in humid regions. Therefore, the research on badlands in humid regions has strong theoretical and practical significance. By taking the Nanxiong Basin, which is located in the humid regions of southern China as the research object, this paper analyzes the scale and spatial distribution variation characteristics of redbed badlands and builds a set of factors that influence redbed badlands to explore the driving forces influencing the variation of redbed badlands based on remote sensing images of the American KH-4A satellite from 1969 and a Landsat 8 image from 2017. The result shows that the scale of redbed badlands in the Nanxiong Basin had generally decreased from 1969 to 2017. The area of redbed badlands decreased from 1693.97 hm2 in 1969 to 127.4 hm2 in 2017, with a decrease of 92.48%. The spatial distribution of redbed badlands had gradually changed from the contiguous planar distribution form in 1969 to the dispersed island distribution form in 2017, forming four agglomerations. The influence degree of the driving forces for the scale variation of redbed badlands is in the order of lithology > road > aspect > residential locations > slope > water system > vegetation > garden plots. Among these driving forces, except vegetation and garden plots, which have a negative correlation with the variation of redbed badlands, other factors have a positive correlation. Lithology is positively correlated with the variation of redbed badlands and has the strongest influence on the redbed badlands of all the influencing factors. The road factor is second to the lithological factor; the more accessible an area is, the stronger the human influence will be and the more serious the damage to vegetation will be, which easily cause surface vegetation damage, induce land degradation, and form redbed badlands.

Additional file 2: Figure S2. Analysis of copy number variation and single nucleotide polymorphism of 15 model immune genes.

Additional file 1: Figure S1. GO (A) and KEGG(B) enrichment analysis of DEIGs.

Background: RNA binding proteins (RBPs) are now under discussion as novel promising bio-markers for patients with colon cancer. The purpose of our study is to identify several RBPs related to the progression and prognosis of colon cancer, and to further investigate the mechanism of their influence on tumor progression. Methods: The transcriptome data of colon cancer as well as clinical characteristics used in this study were downloaded from the The Cancer Genome Atlas (TCGA) database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene set enrichment analysis (GSEA) were performed to elucidate the gene functions and relative pathways. Cox and lasso regression analysis were used to analyze the effect of immune genes on the prognosis of breast cancer. Immune risk scoring model was constructed based on the statistical correlation between hub immune genes and survival. Meanwhile, multivariate cox regression analysis was utilized to investigate whether the immune genes risk score model was an independent factor for predicting the prognosis of breast cancer. Nomogram was constructed to comprehensively predict the survival rate of breast cancer. P< 0.05 was considered to be statistically significant. Results: The results of the difference analysis showed that 473 RBPs exhibited differential expression between normal and colon cancer tissues (pConclusion: Collectively, RBPs played an essential role in the progression and prognosis of colon cancer by regulating multiple biological pathways. Furthermore, RBPs risk score was an independent predictive factor of colon cancer, indicating a poor survival.

Objective Increasing evidence has indicated an association between immune micro-environment in breast cancer and clinical outcomes. The aim of this research is to comprehensively investigate the effect of tumor immune genes on the prognosis of breast cancer patients. Methods 2498 immune genes were downloaded from ImmPort database. Additionally, we identified and downloaded the transcriptome data of patients with breast cancer from the TCGA database through the R package, as well as relevant clinical information. Survival R package was applied in survival analyses for hub-genes. Cox regression analysis was used to analyze the effect of immune genes on the prognosis of breast cancer. Immune risk scoring model was constructed based on the statistical correlation between hub immune genes and survival. Meanwhile, multivariate cox regression analysis was utilized to investigate whether the immune genes risk score model was an independent factor for predicting the prognosis of breast cancer. Nomogram was constructed to comprehensively predict the survival rate of breast cancer. P

Objective: Transarterial chemoembolization (TACE) is the standard treatment for unresectable intermediate hepatocellular carcinoma. Drug-eluting beads (DEB)-TACE is a promising approach expected to improve the efficiency and safety of conventional (c) TACE. However, controversy remains whether DEB-TACE performs better than cTACE. This meta-analysis aimed to compare cTACE and DEB-TACE in terms of overall survival (OS), adverse events, and response rate. Literature search was performed in PubMed, Cochrane, Embase, and Web of Science. Complete response (CR), partial response (PR), disease control (DC), stable disease (SD), OS, and major complications were compared between these two modalities. The pooled relative risk and 95% confidence interval were calculated for assessment. Six randomized controlled trials were included for further analysis after a comprehensive search. No significant difference was found in overall response at 3, 6, 9, and 12 months, CR, PR, DC (SD), OS and complications between cTACE and DEB-TACE. Conclusion: DEB-TACE had similar therapeutic effects to those of cTACE. Furthermore, major complications in both therapies were similar. The superiority of DEB-TACE over cTACE remains unclear, and further research with high-quality evidence is needed.

EP67 is a second-generation, human C5a-derived decapeptide agonist of C5a Receptor 1 (C5aR1/CD88) that selectively activates mononuclear phagocytes over neutrophils to potentiate protective innate and adaptive immune responses while potentially minimizing neutrophil-mediated toxicity. Pro(7) and N-methyl-Leu(8) (Me-Leu(8)) amino acid residues within EP67 likely induce backbone structural changes that increase potency and selective activation of mononuclear phagocytes over neutrophils vs. first-generation EP54. Low coupling efficiency between Pro(7) and Me-Leu(8) and challenging purification by HPLC, however, greatly increase scale-up costs of EP67 for clinical use. Thus, the goal of this study was to determine whether replacing Pro(7) and/or Me-Leu(8) with large-scale amenable amino acid residues predicted to induce similar structural changes (cyclohexylalanine(7) and/or leucine(8)) sufficiently preserves EP67 activity in primary human mononuclear phagocytes and neutrophils. We found that, depending on the secreted cytokine and mononuclear phagocyte, EP67 analogs had (i.) similar or lower (29 to 39%) potency and similar, increased (9.5 to 45%), or decreased (5 to 23%) efficacy for IL-6 and TNF-α secretion from mononuclear phagocytes and (ii.) similar potency and similar or decreased (21% to 24%) efficacy for myeloperoxidase secretion from human neutrophils without affecting selective activation of human mononuclear phagocytes. Thus, replacing Pro(7) and/or Me-Leu(8) with large-scale amenable amino acid residues predicted to induce similar structural changes is a suitable strategy to overcome scale-up challenges with EP67.

Semisynthetic artemisinins and other bioactive peroxides are best known for their powerful antimalarial activities, and they also show substantial activity against schistosomes-another hemoglobin-degrading pathogen. Building on this discovery, we now describe the initial structure-activity relationship (SAR) of antischistosomal ozonide carboxylic acids OZ418 (2) and OZ165 (3). Irrespective of lipophilicity, these ozonide weak acids have relatively low aqueous solubilities and high protein binding values. Ozonides with para-substituted carboxymethoxy and N-benzylglycine substituents had high antischistosomal efficacies. It was possible to increase solubility, decrease protein binding, and maintain the high antischistosomal activity in mice infected with juvenile and adult Schistosoma mansoni by incorporating a weak base functional group in these compounds. In some cases, adding polar functional groups and heteroatoms to the spiroadamantane substructure increased the solubility and metabolic stability, but in all cases decreased the antischistosomal activity.

BackgroundThe cardiotoxicity of isoniazid on zebrafish embryos and its underlying mechanism is unclear.MethodsHere, we exposed zebrafish embryos at 4 h post-fertilization to different levels of isoniazid and recorded the morphology and number of malformed and dead embryos under the microscope.ResultsThe high concentration of isoniazid group showed more malformed and dead embryos than the low concentration of isoniazid group and control group. The morphology of the heart and its alteration were visualized using transgenic zebrafish (cmlc2: GFP) and confirmed by in situ hybridization. The negative effects of isoniazid on the developing heart were characterized by lower heart rate and more heart looping disorders. Mechanistically, PCR showed decreased expression of heart-specific transcription factors when exposed to isoniazid. Oxidative stress was induced by isoniazid in cardiomyocytes, mediated by decreased activities of catalase and superoxide dismutase, which were rescued by scavengers of reactive oxygen species.ConclusionIn conclusion, this study demonstrated that isoniazid led to heart looping disturbance by the downregulation of cardiac-specific transcription factors and induction of cardiomyocyte apoptosis.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease and hypocomplementemia signifies disease activity. Several studies have shown that calcium may help maintain optimum function of immune system and metabolism in SLE. The aim of our study was to analyze the relationship between total serum calcium level and SLE activity. A total of 66 patients with SLE and 214 healthy controls were included in this study. Our results showed lower serum levels of calcium ( P < .001), complement C3 ( P < .001), complement C4 ( P < .001), and albumin ( P < .001) in patients with SLE. A negative correlation was found between serum calcium level and systemic lupus erythematosus disease activity index (SLEDAI) rating ( r = −0.394, P = .001). Additionally, serum level of calcium was positively correlated with serum complement C3 level ( r = 0.366, P = .003) in patients with SLE, while no such correlation was found between serum calcium level and complement C4 ( r = −0.190, P = .126). Likewise, patients with SLE with normal serum calcium level showed higher complement C3 level ( P < .01) than that of patients with low serum calcium level. Overall, the results displayed that patients with SLE have lower serum calcium level compared to healthy controls, and the serum calcium level is positively correlated with SLEDAI rating and serum complement C3 level in patients with SLE. In conclusion, the total serum calcium level is negatively correlated with SLE disease activity.

Background: The cardiotoxicity of isoniazid on zebrafish embryos and its underlying mechanism is unclear. Methods: Here, we exposed zebrafish embryos at 4 hours post-fertilization to different levels of isoniazid and recorded the morphology and number of malformed and dead embryos under the microscope. Results: The high concentration of isoniazid group showed more malformed and dead embryos than the low concentration of isoniazid group and control group. The morphology of the heart and its alteration were visualized using transgenic zebrafish (cmlc2: GFP) and confirmed by in situ hybridization. The negative effects of isoniazid on the developing heart were characterized by lower heart rate and more heart looping disorders. Mechanistically, PCR showed decreased expression of heart-specific transcription factors when exposed to isoniazid. Oxidative stress was induced by isoniazid in cardiomyocytes, mediated by decreased activities of catalase and superoxide dismutase, which were rescued by scavengers of reactive oxygen species. Conclusion: In conclusion, this study demonstrated that isoniazid led to heart looping disturbance by the downregulation of cardiac-specific transcription factors and induction of cardiomyocyte apoptosis.

Additional file 1. The details of the resistance training.

Background It is very important for clinicians and dieticians to explore reasonable weight management strategies for obese people that address both short-term weight loss and subsequent weight maintenance. We hypothesized that resistance training combined with a high-protein diet would result in similar short-term weight loss but better long-term weight maintenance than either a conventional low-fat diet control or a high-protein diet alone. Methods/design This is an 8-week randomized parallel controlled trial followed by a 24-week observational follow-up study. A 48-week supplementary follow-up study will be carried out if necessary. The study will be conducted between June 2019 and October 2020. The 90 overweight or obese participants will be randomly assigned to the conventional low-fat diet group, the high-protein diet group and the high-protein diet and resistance training combination group. Primary outcomes are body weight change at week 8 and week 24 compared with the baseline level. Discussion High-quality research on the effect of a high-protein diet combined resistance training on weight loss and weight maintenance is limited in the Chinese population. Our study will provide a basis for obesity management in China and will promote the development of exercise- and diet-related studies. Trial registration Chinese Clinical Trial Registry, ChiCTR1900023841. Registered on 14 June 2019.

Hedgehog (Hh) signaling is involved in the initiation and progression of various cancers and is essential for embryonic and postnatal development. This pathway remains in the quiescent state in adult tissues but gets activated upon inflammation and injuries. Inhibition of Hh signaling pathway using natural and synthetic compounds has provided an attractive approach for treating cancer and inflammatory diseases. While the majority of Hh pathway inhibitors target the transmembrane protein Smoothened (SMO), some small molecules that target the signaling cascade downstream of SMO are of particular interest. Substantial efforts are being made to develop new molecules targeting various components of the Hh signaling pathway. Here, we have discussed the discovery of small molecules as Hh inhibitors from the diverse chemical background. Also, some of the recently identified natural products have been included as a separate section. Extensive structure-activity relationship (SAR) of each chemical class is the focus of this review. Also, clinically advanced molecules are discussed from the last 5 to 7 years. Nanomedicine-based delivery approaches for Hh pathway inhibitors are also discussed concisely.

Four cores (GY1, LTY, SZY, GT-2) taken from lowland to mountain sites in southeastern subtropical China were studied. Charcoal and pollen analyses were conducted to examine the regional Holocene fire history and discuss its possible relationship with both climatic changes and anthropogenic activities. Our results show extremely low charcoal influxes between 9.5 and 3.5 cal ka BP, revealing low fire frequency. Meanwhile, high proportions of arboreal pollen demonstrated expansion of subtropical evergreen broadleaf forest. This phase is consistent with heavy precipitation during the early-mid Holocene. After 3.5 cal ka BP., the abrupt increases in fire frequency revealed by core GY1 and LTY were closely related to gradual drying towards the late Holocene, possibly due to the Asian Summer Monsoon weakening and activation of the El Nino Southern Oscillation. Our pollen records also reveal this drying trend after the mid-Holocene, demonstrating a regional retreat of subtropical evergreen forests and local development of Glyptostrobus -dominated wetland community around the LTY and GY1 sites. However, the intensified fires after 3.5 cal ka BP probably resulted mainly from increasing human activities during the Shang-Zhou Bronze age. Pollen results show severe damage of forest by fires, indicated by notable decrease of arboreal pollen and increase of Dicranopteris and herbs. After 2.0 ka, obvious growth of Poaceae, Dicranopteris and Pinus recorded in the GY1 and LTY cores demonstrate agriculture development in low-altitude plains and hills, coinciding with the first human population boom and big progress in agricultural technology during the Warring States to Western Han Dynasty period. Signs of profound human impacts and extensive agriculture in South China appeared after 1.0 cal ka BP, which is revealed by frequent local fires and intensified anthropogenic impact around the mountains sites (SZY and GT-2). Generally, our results reveal a gradual expansion of anthropogenic activities into elevated areas.

Pingtan Island (Fujian, China) was severely impacted by a group of three typhoons in a sequence of Nepartak, Meranti, and Megi during the summer of 2016. Field investigations were conducted on the island before and after the typhoons using high-precision RTK GPS technology and surveying methods, and we analyzed the morphological responses of three types of coastal dunes (coastal foredunes, climbing dunes, and coastal sand sheets) to the typhoon group. The maximum height decrease among coastal foredunes was 2.89 m after the typhoon group landed; dune volume increased by 0.9%, and the windward side showed a slight height increase, whereas that of the slope crest and leeward slope were slightly lower than the values before the typhoon group landed. The maximum height decrease among climbing dunes was 1.43 m, and dune volume decreased slightly by 0.1%; the height change among climbing dunes differed in magnitude between sites. Among coastal sand sheets, the maximum height increase was 0.75 m, and dune volume increased by 1.5%; the height of frontal coastal sand sheets increased markedly as result of storm surge washover deposits, whereas the heights barely changed at the middle and trailing edges. The above results suggest that the typhoon group imposed significant morphological changes on coastal dunes. However, the features of morphological responses differed between the three types of coastal dunes studied, and also among dunes of the same type based on local characteristics. Furthermore, coastal dunes showed no cumulative effects in their responses to the typhoon group, despite the individual typhoon impacts on coastal dune morphology.

Research on the impact of urbanization on carbon emissions has great significance to the development of low-carbon cities. Although various studies have found a causal relationship between urbanization and carbon emissions, the mechanisms by which land urbanization (especially the spatial agglomeration changes of construction land), population urbanization, and economic urbanization affect carbon emissions are still unclear. This paper presents a comprehensive analysis of the impact of urbanization on carbon emissions in the Pearl River Delta region from 1990 to 2014. The data were analyzed on the basis of a spatial agglomeration function, grey correlation model, Kuznets curve model, etc., according to three aspects of urbanization, namely, land urbanization, population urbanization, and economic urbanization. The associated Kuznets curve relationships between these three aspects of urbanization and carbon emissions were assessed to explore the mechanisms of influence. The main results were as follows. (1) From 1990 to 2014, carbon emissions increased significantly in the Pearl River Delta region from 18.6 × 106 t to 151.31 × 106 t, of which carbon emissions increased much faster from 2000 to 2013. Guangzhou and Shenzhen were the cities with the largest carbon emissions in the Pearl River Delta region. (2) The influence of urbanization on carbon emissions in the Pearl River Delta region showed that economic urbanization had the most obvious impact on carbon emissions followed by land urbanization. Population urbanization had a minimal impact on carbon emissions. The land urbanization and economic urbanization displayed a Kuznets curve relationship with carbon emissions, and the respective models were as follows: y = 145.78x − 839.87x2 − 2.84, y = 0.51x − 0.005x2 + 1.56. (3) The composition structure of carbon emissions showed that priority should be given to emissions from energy consumption and industrial production. Frequent changes of land use were also an important reason for the increase in carbon emissions. The Pearl River Delta region should aim for the construction of low-carbon cities as a goal and attach importance to the harmonious development of the economy and environment in its policies.

N,N′-Diaryl ureas have recently emerged as a new antischistosomal chemotype. We now describe physicochemical profiling, in vitro ADME, plasma exposure, and ex vivo and in vivo activities against Schistosoma mansoni for twenty new N,N′-diaryl ureas designed primarily to increase aqueous solubility, but also to maximize structural diversity. Replacement of one of the 4-fluoro-3-trifluoromethylphenyl substructures of lead N,N′-diaryl urea 1 with azaheterocycles and benzoic acids, benzamides, or benzonitriles decreased lipophilicity, and in most cases, increased aqueous solubility. There was no clear relationship between lipophilicity and metabolic stability, although all compounds with 3-trifluoromethyl-4-pyridyl substructures were metabolically stable. N,N′-diaryl ureas containing 4-fluoro-3-trifluoromethylphenyl, 3-trifluoromethyl-4-pyridyl, 2,2-difluorobenzodioxole, or 4-benzonitrile substructures had high activity against ex vivo S. mansoni and relatively low cytotoxicity. N,N-diaryl ureas with 3-trifluoromethyl-4-pyridyl and 2,2-difluorobenzodioxole substructures had the highest exposures whereas those with 4-fluoro-3-trifluoromethylphenyl substructures had the best in vivo antischistosomal activities. There was no direct correlation between compound exposure and in vivo activity.

We describe a new 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU)-mediated coupling reaction to produce 2-imino benzo[e]-1,3-oxazin-4-ones from salicylic acids and anilines. Mechanistic studies support a reaction pathway in which HATU mediates carbon transfer to the initially formed salicylanilides to form in succession reactive tetramethylisouronium and N-acyl(dimethyl)isouronium intermediates, which then undergo imine-iminium exchange to generate the desired oxazinones.

Chemoresistance and inadequate therapeutics transport across the blood brain barrier (BBB) remain the major barriers to treating medulloblastoma (MB). Hedgehog (Hh) and IGF/PI3K pathways regulate tumor cell proliferation and resistance in MB. Current Hh inhibitors are effective initially to treat SHH-MB but acquire resistance. Herein, we showed that Hh inhibitor MDB5 and BRD4/PI3K dual inhibitor SF2523 synergistically inhibited the proliferation of DAOY and HD-MB03 cells when used in combination. Treatment of these MB cells with the combination of MDB5 and SF2523 significantly decreased colony formation and expression of MYCN, p-AKT, and cyclin D1 but significantly increased in Bax expression, compared to individual drugs. We used our previously reported copolymer mPEG-b-PCC-g-DC copolymer, which showed 8.7 ± 1.0 and 6.5 ± 0.1% loading for MDB5 and SF2523 when formulated into nanoparticles (NPs). There was sustained drug release from NPs, wherein 100% of MDB5 was released in 50 h, but only 60% of SF2523 was released in 80 h. Targeted NPs prepared by mixing 30:70 ratio of COG-133-PEG-b-PBC and mPEG-b-PCC-g-DC copolymer delivered a significantly higher drug concentration in the cerebellum at 6 and 24h after intravenous injection into orthotopic SHH-MB tumor-bearing NSG mice . Moreover, systemic administration of COG-133-NPs loaded with MDB5 and SF2523 resulted in decreased tumor burden compared to non-targeted drug-loaded NPs, without any hepatic toxicity. In conclusion, our nanomedicine of MDB5 and SF2523 offers a novel therapeutic strategy to treat chemoresistant MB.

A number of new polybrominated adamantanes were formed by rearrangements and bromination of 2,2,6,6-tetrabromoadamantane under Friedel-Crafts conditions. Protoadamantane-4,10-dione, 10-acetoxyprotoadamantan-4-one, 1,2,6-triacetoxyadamantane and 5,6-diacetoxyadamantan-2-one were formed by successive semipinacol and protoadamantane-adamantane rearrangements of 5,6-dibromoadamantan-2-one and 5,6-dibromoadamantan-2-ol. This work may open up new pathways for the synthesis of 1,2,6-trisubstituted adamantanes.

Building on insights gained from the discovery of the antimalarial ozonide arterolane (OZ277), we now describe the structure–activity relationship (SAR) of the antimalarial ozonide artefenomel (OZ439). Primary and secondary amino ozonides had higher metabolic stabilities than tertiary amino ozonides, consistent with their higher pKa and lower log D7.4 values. For primary amino ozonides, addition of polar functional groups decreased in vivo antimalarial efficacy. For secondary amino ozonides, additional functional groups had variable effects on metabolic stability and efficacy, but the most effective members of this series also had the highest log D7.4 values. For tertiary amino ozonides, addition of polar functional groups with H-bond donors increased metabolic stability but decreased in vivo antimalarial efficacy. Primary and tertiary amino ozonides with cycloalkyl and heterocycle substructures were superior to their acyclic counterparts. The high curative efficacy of these ozonides was most often associ...

Background It is very important for clinicians and dieticians to explore reasonable weight management strategies for obese people that address both short-term weight loss and subsequent weight maintenance. We hypothesized that resistance training combined with a high-protein diet would result in similar short-term weight loss but better long-term weight maintenance than either conventional low-fat diet control or high-protein diet alone.Methods/design This is an 8-week randomized parallel controlled trial followed by a 24-week observational follow-up study. A 48-week supplementary follow-up study will be carried out if necessary. The study will be conducted between June 2019 and October 2020. The 90 overweight or obese participants will be randomly assigned to the conventional low-fat diet group, the high-protein diet group and the high-protein diet and resistance training combination group. Primary outcomes are body weight changes at week 8 and week 24 compared with the baseline level.Discussion High-quality research on the effect of a high-protein diet combined resistance training on weight loss and weight maintenance is limited in Chinese population. Our study will provide a basis for obesity management in China, and promote the development of exercise and diet-related studies.Trials registration ChiCTR1900023841, 14 June 2019

Social-ecological system (SES) resilience involves the large information and complex relationships of nature, society and economy. To promote multi-disciplinary integration to jointly balance current well-being and long-term sustainability, it is necessary to sort resilience studies on different perspectives into a comprehensive framework to establish interdisciplinary consensus. Based on literature analysis and review, this paper presents an analytical framework for resilience in regional management, and gives a review of SES resilience studies in terms of mechanism, assessment, and management. We outline the current state of resilience research, identify the remaining challenges, and make key recommendations for future research. Our recommendations include promoting interdisciplinary consensus, emphasising dynamic adaptation processes, synthesizing multiple systems and scales, building comprehensive databases, and using mixed methods approach. The paper offers a framework for researchers, practitioners and policy makers to have a more comprehensive understanding of resilience as a whole, and thus helps navigate more fully the challenge of adapting complex resource and environmental problems.

Background It is very important for clinicians and dieticians to explore reasonable weight management strategies for obese people that address both short-term weight loss and subsequent weight maintenance. We hypothesized that resistance training combined with a high-protein diet would result in similar short-term weight loss but better long-term weight maintenance than either conventional low-fat diet control or high-protein diet alone.Methods/design This is an 8-week randomized parallel controlled trial followed by a 24-week observational follow-up study. A 48-week supplementary follow-up study will be carried out if necessary. The study will be conducted between June 2019 and October 2020. The 90 overweight or obese participants will be randomly assigned to the conventional low-fat diet group, the high-protein diet group and the high-protein diet and resistance training combination group. Primary outcomes are body weight changes at week 8 and week 24 compared with the baseline level.Discussion High-quality research on the effect of a high-protein diet combined resistance training on weight loss and weight maintenance is limited in Chinese population. Our study will provide a basis for obesity management in China, and promote the development of exercise and diet-related studies.Trials registration ChiCTR1900023841, 14 June 2019

The aryl hydantoin 1 (Ro 13-3978) was identified in the early 1980s as a promising antischistosomal lead compound. However, this series of aryl hydantoins produced antiandrogenic side effects in the host, a not unexpected outcome given their close structural similarity to the antiandrogenic drug nilutamide. Building on the known SAR of this compound series, we now describe a number of analogs of 1 designed to maximize structural diversity guided by incorporation of substructures and functional groups known to diminish ligand-androgen receptor interactions. These analogs had calculated polar surface area (PSA), measured LogD7.4, aqueous kinetic solubility, and estimated plasma protein binding values in ranges predictive of good ADME profiles. The principal SAR insight was that the hydantoin core of 1 is required for high antischistosomal activity. We identified several compounds with high antischistosomal efficacy that were less antiandrogenic than 1. These data provide direction for the ongoing optimization of antischistosomal hydantoins.

Complex changes in carbon sources and sinks caused by rapid urbanization have been observed with extensive changes in the quantity, structure, and spatial pattern of land use types. Based on the modified Carnegie-Ames-Stanford Approach model and on gray relational analysis, we analyzed the influence of land use changes on carbon sinks and emissions in Guangzhou from 2000 to 2012. The aim was to identify suitable options for built-up land expansion that would allow for minimal carbon losses. The key results were as follows: (1) Built-up land increased by 118.91% in Guangzhou city over the study period, with this expansion taking the form of concentric circles extending around the old Yuexiu district. (2) Carbon emissions over the period of analysis significantly exceeded carbon sink capabilities. The total carbon sink decreased by 30.02%, from 535.40 × 103 t to 374.6 × 103 t. Total carbon emissions increased by 1.89 times, from 13.73 × 106 t to 39.67 × 106 t; 80% of carbon emissions were derived from energy consumption. (3) There were large differences in the extent of carbon sink losses at different scales of built-up land expansion and land use change. In Guangzhou, the loss of carbon sink is small when cultivated land (though not prime farmland) and water bodies are converted to built-up land on a small scale. The loss of carbon sink is much smaller when grasslands are converted to built-up land on a large scale. However, forested land, which has excellent carbon sink functions, should not be converted. (4) Changes in carbon sinks were mainly affected by natural factors and land urbanization. Changes in carbon emissions were mainly affected by population urbanization, economic urbanization, and land urbanization. (5) To achieve “economical and intensive use of land”, “urban growth boundary” and “ecological red lines” should be determined for government policies on land use management. These factors have great significance for “increasing carbon sinks and reducing carbon emissions” in urban ecological systems.

Water supply is an important freshwater ecosystem service provided by ecosystems. Water shortages resulting from spatio-temporal heterogeneity of climate condition or human activities present serious problems in the Guizhou Province of southwest China. This study aimed to analyze the spatio-temporal changes of water supply service using the Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST) model, explore how climate and land-use changes impact water supply provision, and discuss the impact of parameters associated with climate and land-use in the InVEST model on water supply in the region. We used data and the model to forecast trends for the year 2030 and found that water supply has been declining in the region at the watershed scale since 1990. Climate and land-use change played important roles in affecting the water supply. Water supply was overwhelmingly driven by the reference evapotranspiration and annual average precipitation, while the plant evapotranspiration coefficients for each land-use type had a relatively small effect. The method for sensitivity analysis developed in this study allowed exploration of the relative importance of parameters in the InVEST water yield model. The Grain-for-Green project, afforestation, and urban expansion control should be accelerated in this region to protect the water supply.

Urea carboxylic acids, products of aryl hydantoin hydrolysis, were recently identified as a new antischistosomal chemotype. We now describe a baseline structure–activity relationship (SAR) for this compound series. With one exception, analogs of lead urea carboxylic acid 2 were quite polar with Log D7.4 values ranging from −1.9 to 1.8, had high aqueous solubilities in the range of 25–100 µg/mL, and were metabolically stable. None of the compounds had measurable in vitro antischistosomal activity or cytotoxicity, but four of these had moderate worm burden reduction (WBR) values of 42–70% when they were administered as single 100 mg/kg oral doses to S. mansoni-infected mice. These data indicate that with the exception of the gem-dimethyl substructure and the distal nitrogen atom of the urea functional group, the rest of the structure of 2 is required for in vivo antischistosomal activity.

2-Azaadamantan-6-one and its Boc and ethylene ketal derivatives were synthesized from 9-oxo endo-bicyclo[3.3.1]non-6-ene-3-carboxylic acid. Similarly, the Cbz, Boc, and ethylene ketal derivatives of 2-azaadamantan-4-one were synthesized from endo-bicyclo[3.3.1]non-6-ene-3-carboxylic acid. Key steps were Curtius rearrangements to form benzyl carbamates, followed by spontaneous intramolecular attack of the carbamate nitrogen on transient bromonium ion or epoxide intermediates to effect ring closure to azaadamantane intermediates. The reaction sequence leading to 2-azaadamantan-6-one is consistent with the formation of a transient tetracyclic keto aziridine intermediate.

Locations of city features, e.g., city centers, roads, railways, and rivers, may impact urban carbon sinks. Therefore, the effects of city features on spatial variations of urban carbon sinks were investigated using geographic proximity data. The main results were as follows. (1) Carbon sink function varied in a complex manner with distance from the city center and with city size. The carbon sink per unit area increased with distance from the prefecture-level city center (0–30 km), with the dominant influence occurring within a 9 km radius. The lowest carbon sink per unit area was observed at a distance of 12 km from the city center of the provincial capital city (Guangzhou) and special economic zone (Shenzhen), which may be suburban industrial zones. (2) Carbon sinks decreased with increases in road grades as a result of the different functions and traffic flow, and carbon sinks were lowest near city express ways. For highways, carbon sinks were lower near highway entrances and exits. Carbon sinks around ordinary railways were higher than those around subways and light rail, but carbon sink characteristics grew more complex with increasing distances from subways and light rail. (3) Rivers were closely related to the urban layout. Grade I (i.e., larger) rivers were associated with lower carbon sinks, and carbon sink characteristics became increasingly complex around larger rivers. Within a 0–1000 m distance of all rivers, the carbon sink per unit area increased rapidly, but carbon sink characteristics differed slightly for grade I rivers. This study implies that it is important to take urbanization spatial position effects into account while assessing regional carbon sinks during urbanization and development.

The singular structure of artemisinin, with its embedded 1,2,4-trioxane heterocycle, has inspired the discovery of numerous semisynthetic artemisinin and structurally diverse synthetic peroxide antimalarials, including ozonides OZ277 (arterolane) and OZ439 (artefenomel). Despite the critical importance of artemisinin combination therapies (ACTs), the precise mode of action of peroxidic antimalarials is not fully understood. However, it has long been proposed that the peroxide bond in artemisinin and other antimalarial peroxides undergoes reductive activation by ferrous heme released during hemoglobin digestion to produce carbon-centered radicals that alkylate heme and parasite proteins. To probe the mode of action of OZ277 and OZ439, this paper now describes initial studies with monoclonal antibodies that recognize the alkylation signature (sum of heme and protein alkylation) of these synthetic peroxides. Immunofluorescence experiments conducted with ozonide-treated parasite cultures showed that ozonide alkylation is restricted to the parasite, as no signal was found in the erythrocyte or its membrane. In Western blot experiments with ozonide-treated Plasmodium falciparum malaria parasites, distinct protein bands were observed. Significantly, no protein bands were detected in parallel Western blot experiments performed with lysates from ozonide-treated Babesia divergens, parasites that also proliferate inside erythrocytes but, in contrast to P. falciparum, do not catabolize hemoglobin. However, subsequent immunoprecipitation experiments with these antibodies failed to identify the P. falciparum proteins alkylated by OZ277 and OZ439. To the best of the authors’ knowledge, this shows for the first time that antimalarial ozonides, such as the artemisinins, alkylate proteins in P. falciparum.

Objectives Praziquantel is the only drug available for the treatment of schistosomiasis and the state of the exhausted drug discovery pipeline is alarming. We restarted investigations on the abandoned antischistosomal Ro 13-3978, an aryl hydantoin discovered in the early 1980s by Hoffmann La-Roche. Methods Newly transformed schistosomula and adult Schistosoma mansoni were studied in the presence of Ro 13-3978 in vitro. The metabolic stability of Ro 13-3978 was determined in vitro using human and mouse liver S9 fractions. Dose–response relationship, stage specificity, hepatic shift and scanning electron microscopy studies were carried out in S. mansoni-infected mice. In addition, efficacy experiments were conducted in rodents infected with Echinostoma caproni and Fasciola hepatica as well as in S. mansoni-infected immunocompromised nude (Foxn1nu) mice. Results Ro 13-3978 showed minor in vitro activity and no damage to the tegument was found. No cytotoxicity was detected for Ro 13-3978. Ro 13-3978 was metabolically stable. ED50 values of 138.9 and 14.6 mg/kg were calculated for the treatment of juvenile and adult S. mansoni infections, respectively, with a single oral dose of Ro 13-3978. SEM studies revealed severe damage to the worms 48 h post-treatment of infected mice. A single oral dose of Ro 13-3978 (100 mg/kg) administered to S. mansoni-infected (Foxn1nu) mice reduced the worm burden by 88%. Ro 13-3978 was not active against E. caproni and F. hepatica in vivo. Conclusions Ro 13-3978 has excellent antischistosomal properties in vivo. Structure–activity relationship studies with the aryl hydantoins have been launched in order to elucidate active pharmacophores, further investigate the mechanism of action and to identify a derivative with minimal antiandrogenic effects.