SS-31 efficacy in a mouse model of Friedreich ataxia by upregulation of frataxin expression.

Friedreich ataxia (FRDA) is a serious hereditary neurodegenerative disease, mostly accompanied with hypertrophic cardiomyopathy, caused by the reduced expression of frataxin (FXN). However, there is still no effective treatment. Our previous studies have shown that SS-31, a mitochondrion-targeted peptide, is capable to upregulate the expression of FXN and improve the mitochondrial function in cells derived from FRDA patients. To further explore the potential of SS-31, we used the GAA expansion-based models, including Y47 and YG8R (Fxn KIKO) mice, primary neurons and macrophages from the mice and cells derived from FRDA patients. After once-daily intraperitoneal injection of 1 mg/kg SS-31 for 1 month, we observed the significant improvement of motor function. The vacuolation in dorsal root ganglia, lesions in dentate nuclei and the lost thickness of myelin sheath of spinal cord were all repaired after SS-31 treatment. In addition, the hypertrophic cardiomyocytes and disarrayed abnormal Purkinje cells were dramatically reduced. Interestingly, we found that SS-31 treatment upregulated FXN expression not only at the translational levels as observed in cell culture but also at mRNA levels in vivo. Consequently, mitochondrial morphology and function were greatly improved in all tested tissues. Importantly, our data provided additional evidence that the maintenance of the therapeutic benefits needed continuous drug administration. Taken together, our findings have demonstrated the effectiveness of SS-31 treatment through the upregulation of FXN in vivo and offer guidance of the potential usage in the clinical application for FRDA.

Congener Variation of Genetic Dependent-Developmental Toxicology in Two Emerging Classes of Dioxin-like Compounds.

Emerging classes of dioxin-like compounds (DLCs) like hydroxylated/methoxylated polybrominated diphenyl ethers (HO-/MeO-PBDEs) and polychlorinated diphenyl sulfides (PCDPSs) could lead to diverse adverse outcomes in humans and wildlife, yet knowledge gaps exist in their molecular mechanisms associated with different structures following early life environmental exposure. This study integrated a genetic knockout technique and concentration-dependent reduced zebrafish transcriptome approach (CRZT) to unravel the toxicological pathways underpinning developmental toxicity of four HO-/MeO-PBDEs and five PCDPSs at environmentally relevant doses. Generally, the dependence of aryl hydrocarbon receptor (AhR) on the embryotoxicity and transcriptomic potencies induced by the HO-PBDEs and PCDPSs varied across different congeners. The knockout of the ahr2 gene led to 1.02- to 76.48-fold decreases of DLC-induced embryotoxicities and reduced the transcriptome-based potencies ranging from 1.38 to 2124.74 folds in the CRZT test. The fold changes denoting AhR-mediated potentials significantly increased with the increasing chlorination degrees of MeO-PBDEs and PCDPSs (p < 0.05). Moreover, ahr2 knockout primarily affected the DLC-induced early molecular responses relevant to DNA damage, enzyme activation, and organ development. Our integrated approach revealed the differential role of AhR in mediating the developmental toxicity of emerging DLCs possessing varied structures at environmentally relevant doses.

Bioaccumulation, Trophic Transfer, and Biotransformation of Polychlorinated Diphenyl Ethers in a Simulated Aquatic Food Chain.

Polychlorinated diphenyl ethers (PCDEs) are detected in aquatic environments and demonstrate adverse effects in aquatic organisms. However, data regarding the environmental behavior of PCDEs in aquatic ecosystems are lacking. In the present study, a simulated aquatic food chain (Scenedesmus obliquus-Daphnia magna-Danio rerio) was constructed in a lab setting, and the bioaccumulation, trophic transfer, and biotransformation of 12 PCDE congeners were quantitatively investigated for the first time. The log-transformed bioaccumulation factors (BCFs) of PCDEs in S. obliquus, D. magna, and D. rerio were in the range of 2.94-3.77, 3.29-4.03, and 2.42-2.89 L/kg w.w., respectively, indicating the species-specific bioaccumulation of PCDE congeners. The BCF values increased significantly with the increasing number of substituted Cl atoms, with the exception of CDE 209. The number of Cl atoms at the para and meta positions were found to be the major positive contributing factors for BCFs in the case of the same number of substituted Cl. The lipid-normalized biomagnification factors (BMFs) of S. obliquus to D. magna, D. magna to D. rerio, and the whole food chain for the 12 PCDE congeners ranged at 1.08-2.27, 0.81-1.64, and 0.88-3.64, respectively, suggesting that some congeners had BMFs comparable to PBDEs and PCBs. Dechlorination was the only metabolic pathway observed for S. obliquus and D. magna. For D. rerio, dechlorination, methoxylation, and hydroxylation metabolic pathways were observed. 1H nuclear magnetic resonance (NMR) experiments and theoretical calculations confirmed that methoxylation and hydroxylation occurred at the ortho position of the benzene rings. In addition, reliable quantitative structure-property relationship (QSPR) models were constructed to qualitatively describe the relationships between molecular structure descriptors and BCFs for PCDEs. These findings provide insights into the movement and transformation of PCDEs in aquatic ecosystems.

Genotoxicity Assessment of Haloacetaldehyde Disinfection Byproducts via a Simplified Yeast-Based Toxicogenomics Assay.

Haloacetaldehydes (HALs) represent the third-largest category of disinfection byproducts (DBPs) in drinking water in terms of weight. As a subset of unregulated DBPs, only a few HALs have undergone assessment, yielding limited information regarding their genotoxicity mechanisms. Herein, we developed a simplified yeast-based toxicogenomics assay to evaluate the genotoxicity of five specific HALs. This assay recorded the protein expression profiles of eight Saccharomyces cerevisiae strains fused with green fluorescent protein, including all known DNA damage and repair pathways. High-resolution real-time pathway activation data and protein expression profiles in conjunction with clustering analysis revealed that the five HALs induced various DNA damage and repair pathways. Among these, chloroacetaldehyde and trichloroacetaldehyde were found to be positively associated with genotoxicity, while dichloroacetaldehyde, bromoacetaldehyde, and tribromoacetaldehyde displayed negative associations. The protein effect level index, which are molecular end points derived from a toxicogenomics assay, exhibited a statistically significant positive correlation with the results of traditional genotoxicity assays, such as the comet assay (rp = 0.830 and p < 0.001) and SOS/umu assay (rp = 0.786 and p = 0.004). This yeast-based toxicogenomics assay, which employs a minimal set of gene biomarkers, can be used for mechanistic genotoxicity screening and assessment of HALs and other chemical compounds. These results contribute to bridging the knowledge gap regarding the molecular mechanisms underlying the genotoxicity of HALs and enable the categorization of HALs based on their distinct DNA damage and repair mechanisms.

Exosomes Derived from Hypoxia-Cultured Human Adipose Stem Cells Alleviate Articular Chondrocyte Inflammaging and Post-Traumatic Osteoarthritis Progression.

Osteoarthritis (OA) is the most common age-related degenerative joint disease. Inflammaging, linking inflammation and aging, is found in senescent cells with the secretions of matrix-degrading proteins and proinflammatory cytokines. The senescence-associated secretory phenotype (SASP) plays a very important role in OA progression. However, there remains no effective way to suppress OA progression, especially by suppressing inflammaging and/or the chondrocyte SASP. Recent studies have shown that exosomes derived from hypoxia-cultured BMSCs can regenerate cartilage in OA animal models. Some reports have further indicated that exosomes secreted from MSCs contribute to the efficacy of MSC therapy in OA. However, whether hypoxia-cultured ADSC-secreted exosomes (hypoxia-ADSC-Exos) can alleviate the chondrocyte SASP or OA progression remains unclear. Accordingly, we hypothesized that hypoxia-ADSC-Exos have a beneficial effect on the normal functions of human articular chondrocytes (HACs), can attenuate the SASP of OA-like HACs in vitro, and further suppress OA progression in rats. Hypoxia-ADSC-Exos were derived from ADSCs cultured in 1% O2 and 10% de-Exo-FBS for 48 h. The molecular and cell biological effects of hypoxia-ADSC-Exos were tested on IL1-ß-induced HACs as OA-like HACs in vitro, and the efficacy of OA treatment was tested in ACLT-induced OA rats. The results showed that hypoxia-ADSC-Exos had the best effect on GAG formation in normal HACs rather than those cultured in normoxia or hypoxia plus 2% de-Exo-FBS. We further found that hypoxia-ADSC-Exos alleviated the harmful effect in OA-like HACs by decreasing markers of normal cartilage (GAG and type II collagen) and increasing markers of fibrous or degenerative cartilage (type I or X collagen), matrix degradation enzymes (MMP13 and ADAMT5), and inflammatory cytokines (TNFα and IL-6). More importantly, intra-articular treatment with hypoxia-ADSC-Exos suppressed OA progression, as evidenced by the weight-bearing function test and cartilage GAG quantification in ACLT rats. Moreover, through NGS and bioinformatic analysis, seven potential miRNAs were found in hypoxia-ADSC-Exos, which may contribute to regulating cellular oxidative stress and attenuating cell senescence. In summary, we demonstrated that hypoxia-ADSC-Exos, carrying potent miRNAs, not only improve normal HAC function but also alleviate HAC inflammaging and OA progression. The results suggest that hypoxia-ADSC-Exo treatment may offer another strategy for future OA therapy.

Effects of organic substrates on sulfate-reducing microcosms treating acid mine drainage: Performance dynamics and microbial community comparison.

Bioremediation techniques utilizing sulfate-reducing bacteria (SRB) for acid mine drainage (AMD) treatment have attracted growing attention in recent years, yet substrate bioavailability for SRB is a key factor influencing treatment effectiveness and long-term stability. This study investigated the effects of external organic substrates, including four complex organic wastes (i.e., sugarcane bagasse, straw compost, shrimp shell (SS), and crab shell (CS)) and a small-molecule organic acid (i.e., propionate), on AMD removal performance and associated microbial communities during the 30-day operation of sulfate-reducing microcosms. The results showed that the pH values increased in all five microcosms, while CS exhibited the highest neutralization ability and a maximum alkalinity generation of 1507 mg/L (as CaCO3). Sulfate reduction was more effective in SS and CS microcosms, with sulfate removal efficiencies of 95.6% and 86.0%, respectively. All sulfate-reducing microcosms could remove heavy metals to different degrees, with the highest removal rate of >99.0% observed for aluminum. The removal efficiency of manganese, the most recalcitrant metal, was the highest (96%) in the CS microcosm. Correspondingly, SRB was more abundant in the CS and SS microcosms as revealed by sequencing analysis, while Desulfotomaculum was the dominant SRB in the CS microcosm, accounting for 10.8% of total effective bacterial sequences. Higher abundances of functional genes involved in fermentation and sulfur cycle were identified in CS and SS microcosms. This study suggests that complex organic wastes such as CS and SS could create and maintain preferable micro-environments for active growth and metabolism of functional microorganisms, thus offering a cost-efficient, stable, and environmental-friendly solution for AMD treatment and management.

Heavy Rainfall Events Following the Dry Season Elevate Metal Contamination in Mining-Impacted Rivers: A Case Study of Wenyu River, Qinling, China.

Heavy metal pollution of a mining-impacted river-the Wenyu River-and a short section of the river it joins, the Luo River, were investigated after heavy rainfall following a dry season in March 2015 and during a normal flow season in May 2015. Water samples were collected during these two periods, and sediment samples were obtained in May as the rain washed out the sediments in March. The results showed the following: (1) The Wenyu River was severely polluted by acid mine drainage from an open-pit molybdenum (Mo) mine, and the major pollutants in the water according to Chinese national standard values were acid (pH), sulfate, Cu, Zn, Mn, Ni, and Cd. The major pollutants in the sediment were Cu, Zn, and Cd, as indicated by the geoaccumulation index and potential ecological risk index. (2) The major pollutants in the water were naturally attenuated along the river and met the national standard values after joining the Luo River, except Mn in both water samples and Cd in the samples after rain in March. The major pollutants in the sediments showed an increasing tendency along the Wenyu River and Luo River. (3) The heavy rainfall following the prolonged dry season increased acid and heavy metal contamination in the river, which might be attributed to the dissolution of efflorescent salts and the weathering and erosion of mining residues. Thus, the first heavy rain following a dry season should receive particular attention from mining enterprises and regulators. Several mitigation options and recommendations are also discussed.

Design, Manufacturing, and Control of a Pneumatic-Driven Passive Robotic Gait Training System for Muscle-Weakness in a Lower Limb.

We designed and manufactured a pneumatic-driven robotic passive gait training system (PRPGTS), providing the functions of body-weight support, postural support, and gait orthosis for patients who suffer from weakened lower limbs. The PRPGTS was designed as a soft-joint gait training rehabilitation system. The soft joints provide passive safety for patients. The PRPGTS features three subsystems: a pneumatic body weight support system, a pneumatic postural support system, and a pneumatic gait orthosis system. The dynamic behavior of these three subsystems are all involved in the PRPGTS, causing an extremely complicated dynamic behavior; therefore, this paper applies five individual interval type-2 fuzzy sliding controllers (IT2FSC) to compensate for the system uncertainties and disturbances in the PRGTS. The IT2FSCs can provide accurate and correct positional trajectories under passive safety protection. The feasibility of weight reduction and gait training with the PRPGTS using the IT2FSCs is demonstrated with a healthy person, and the experimental results show that the PRPGTS is stable and provides a high-trajectory tracking performance.

Dependence of Graphene Oxide (GO) Toxicity on Oxidation Level, Elemental Composition, and Size.

The mass production of graphene oxide (GO) unavoidably elevates the chance of human exposure, as well as the possibility of release into the environment with high stability, raising public concern as to its potential toxicological risks and the implications for humans and ecosystems. Therefore, a thorough assessment of GO toxicity, including its potential reliance on key physicochemical factors, which is lacking in the literature, is of high significance and importance. In this study, GO toxicity, and its dependence on oxidation level, elemental composition, and size, were comprehensively assessed. A newly established quantitative toxicogenomic-based toxicity testing approach, combined with conventional phenotypic bioassays, were employed. The toxicogenomic assay utilized a GFP-fused yeast reporter library covering key cellular toxicity pathways. The results reveal that, indeed, the elemental composition and size do exert impacts on GO toxicity, while the oxidation level exhibits no significant effects. The UV-treated GO, with significantly higher carbon-carbon groups and carboxyl groups, showed a higher toxicity level, especially in the protein and chemical stress categories. With the decrease in size, the toxicity level of the sonicated GOs tended to increase. It is proposed that the covering and subsequent internalization of GO sheets might be the main mode of action in yeast cells.

An Intermediate Concentration of Calcium with Antioxidant Supplement in Culture Medium Enhances Proliferation and Decreases the Aging of Bone Marrow Mesenchymal Stem Cells.

Human bone marrow stem cells (HBMSCs) are isolated from the bone marrow. Stem cells can self-renew and differentiate into various types of cells. They are able to regenerate kinds of tissue that are potentially used for tissue engineering. To maintain and expand these cells under culture conditions is difficult-they are easily triggered for differentiation or death. In this study, we describe a new culture formula to culture isolated HBMSCs. This new formula was modified from NCDB 153, a medium with low calcium, supplied with 5% FBS, extra growth factor added to it, and supplemented with N-acetyl-L-cysteine and L-ascorbic acid-2-phosphate to maintain the cells in a steady stage. The cells retain these characteristics as primarily isolated HBMSCs. Moreover, our new formula keeps HBMSCs with high proliferation rate and multiple linage differentiation ability, such as osteoblastogenesis, chondrogenesis, and adipogenesis. It also retains HBMSCs with stable chromosome, DNA, telomere length, and telomerase activity, even after long-term culture. Senescence can be minimized under this new formulation and carcinogenesis of stem cells can also be prevented. These modifications greatly enhance the survival rate, growth rate, and basal characteristics of isolated HBMSCs, which will be very helpful in stem cell research.

Impact of Hurricane Maria on Drinking Water Quality in Puerto Rico.

This study performed a comprehensive assessment of the impact of Hurricane Maria (HM) on drinking water quality in Puerto Rico (PR) by integrating targeted chemical analysis of both inorganic (18 trace elements) and organic trace pollutants (200 micropollutants) with high-throughput quantitative toxicogenomics and in vitro biomarkers-based toxicity assays. Average concentrations of 14 detected trace elements and 20 organic micropollutants showed elevation after HM. Arsenic, sucralose, perfluorooctanoic acid (PFOA), atrazine-2-hydroxy, benzotriazole, acesulfame, and prometon were at significantly (p < 0.05) higher levels in the post-HM than in the pre-HM samples. Thirteen micropollutants, including four pesticides, were only detected in posthurricane samples. Spatial comparison showed higher pollutant and toxicity levels in the samples from northern PR (where eight Superfund sites are located) than in those from southern PR. Distinctive pathway-specific molecular toxicity fingerprints for water extracts before and after HM and at different locations revealed changes in toxicity nature that likely resulted from the impact of HM on drinking water composition. Correlation analysis and Maximum Cumulative Ratio assessment suggested that metals (i.e., arsenic) and PFOA were the top ranked pollutants that have the potential to cause increased risk after HM, providing a possible direction for future water resource management and epidemiological studies.

Crab shell amendments enhance the abundance and diversity of key microbial groups in sulfate-reducing columns treating acid mine drainage.

Substrate amendments composed of crab shell (CS) waste materials have been shown to significantly improve the longevity and performance of acid mine drainage (AMD) treatment systems containing spent mushroom compost (SMC), yet the development of key microbial populations within these systems has not been investigated. To better understand the effects of CS on microbial dynamics in these systems, clone libraries and real-time quantitative PCR (qPCR) were performed on materials from a laboratory-scale AMD treatment system containing SMC and 0 to 100% CS substrate after receiving a continuous flow of AMD for 148 days (428 pore volumes). The proportion of CS in the substrate positively correlated with the diversity of sulfate-reducing bacteria (SRB) and archaeal clones, but negatively correlated with fungal diversity. CS also impacted microbial community structure, as revealed in Unifrac significance and principal coordinate analysis tests. The column containing 100% CS substrate supported 7 different genera of SRB-the most ever observed in an AMD treatment system. Moreover, the copy numbers of functional genes representing fermenters, sulfate reducers, and chitin degraders increased with increasing proportions of CS. These observations agree well with the chemical performance data, further validating that by supporting more abundant key microbial groups, chitinous substrates may provide benefits for improving both the longevity and performance of AMD treatment systems, and may provide similar benefits for the treatment of other environmental contaminants that are amenable to anaerobic bioremediation.Key points• Crab shell improves the longevity and performance of acid mine drainage treatment.• The diversity of sulfate-reducing bacteria is enhanced with crab shell amendments.• Crab shell supports more abundant key microbial groups than spent mushroom compost.

Discoidin Domain Receptors 1 Inhibition Alleviates Osteoarthritis via Enhancing Autophagy.

We recently reported that the chondrocyte-specific knockout of discoidin domain receptors 1 (Ddr1) delayed endochondral ossification (EO) in the growth plate by reducing the chondrocyte hypertrophic terminal differentiation, and apoptosis. The biologic and phenotypic changes in chondrocytes in the articular cartilage with osteoarthritis (OA) are similar to the phenomena observed in the process of EO. Additionally, autophagy can promote chondrocyte survival and prevent articular cartilage from degradation in OA. On this basis, we explored the effect of Ddr1 inhibition on OA prevention and further investigated the roles of autophagy in treating OA with a Ddr1 inhibitor (7 rh). The anterior cruciate ligament transection (ACLT)-OA model was used to investigate the role of 7 rh in vivo. Forty 8-week-old mice were randomly assigned to four groups, including the sham group, ACLT group, and two treated groups (ACLT with 7 rh 6.9 nM or 13.8 nM). According to the study design, normal saline or 7 rh were intra-articular (IA) injected into studied knees 3 times per week for 2 weeks and then once per week for 4 weeks. The results showed that 7 rh treatment significantly improved the functional performances (the weight-bearing ability and the running endurance), decreased cartilage degradation, and also reduced the terminal differentiation markers (collagen type X, Indian hedgehog, and matrix metalloproteinase 13). Moreover, 7 rh decreased chondrocyte apoptosis by regulating chondrocyte autophagy through reducing the expression of the mammalian target of rapamycin and enhancing the light chain 3 and beclin-1 expression. These results demonstrated that the IA injection of 7 rh could reduce the chondrocyte apoptosis and promote chondrocyte autophagy, leading to the attenuation of cartilage degradation. Our observations suggested that the IA injection of 7 rh could represent a potential disease-modifying therapy to prevention OA progression.

(-)-Epigallocatechin-3-Gallate Decreases Osteoclastogenesis via Modulation of RANKL and Osteoprotegrin.

Osteoporosis is the second most common epidemiologic disease in the aging population worldwide. Previous studies have found that frequent tea drinkers have higher bone mineral density and less hip fracture. We previously found that (-)-epigallocatechin gallate (EGCG) (20⁻100 µmol/L) significantly suppressed receptor activator of nuclear factor-kB ligand (RANKL)-induced osteoclastogenesis and pit formation via inhibiting NF-κB transcriptional activity and nuclear transport of NF-κB in RAW 264.7 cells and murine primary bone marrow macrophage cells. The most important regulation in osteoclastogenesis is the receptor activator of nuclear factor-kB/RANKL/osteoprotegrin (RANK/RANKL/OPG) pathway. In this study, we used the coculture of RAW 264.7 cells and the feeder cells, ST2, to evaluate how EGCG regulated the RANK/RANKL/OPG pathway in RAW 264.7 cells and ST2 cells. We found EGCG decreased the RANKL/OPG ratio in both mRNA expression and secretory protein levels and eventually decreased osteoclastogenesis by TRAP (+) stain osteoclasts and TRAP activity at low concentrations-1 and 10 µmol/L-via the RANK/RANKL/OPG pathway. The effective concentration can be easily achieved in daily tea consumption. Taken together, our results implicate that EGCG could be an important nutrient in modulating bone resorption.

(-)-Epigallocatechin-3-Gallate (EGCG) Enhances Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells.

Osteoporosis is the second most-prevalent epidemiologic disease in the aging population worldwide. Cross-sectional and retrospective evidence indicates that tea consumption can mitigate bone loss and reduce risk of osteoporotic fractures. Tea polyphenols enhance osteoblastogenesis and suppress osteoclastogenesis in vitro. Previously, we showed that (-)-epigallocatechin-3-gallate (EGCG), one of the green tea polyphenols, increased osteogenic differentiation of murine bone marrow mesenchymal stem cells (BMSCs) by increasing the mRNA expression of osteogenesis-related genes, alkaline phosphatase activity and, eventually, mineralization. We also found that EGCG could mitigate bone loss and improve bone microarchitecture in ovariectomy-induced osteopenic rats, as well as enhancing bone defect healing partially via bone morphogenetic protein 2 (BMP2). The present study investigated the effects of EGCG in human BMSCs. We found that EGCG, at concentrations of both 1 and 10 µmol/L, can increase mRNA expression of BMP2, Runx2, alkaline phosphatase (ALP), osteonectin and osteocalcin 48 h after treatment. EGCG increased ALP activity both 7 and 14 days after treatment. Furthermore, EGCG can also enhance mineralization two weeks after treatment. EGCG without antioxidants also can enhance mineralization. In conclusion, EGCG can increase mRNA expression of BMP2 and subsequent osteogenic-related genes including Runx2, ALP, osteonectin and osteocalcin. EGCG further increased ALP activity and mineralization. Loss of antioxidant activity can still enhance mineralization of human BMSCs (hBMSCs).

A Comprehensive Study on the Internet of Underwater Things: Applications, Challenges, and Channel Models.

The Internet of Underwater Things (IoUT) is a novel class of Internet of Things (IoT), and is defined as the network of smart interconnected underwater objects. IoUT is expected to enable various practical applications, such as environmental monitoring, underwater exploration, and disaster prevention. With these applications, IoUT is regarded as one of the potential technologies toward developing smart cities. To support the concept of IoUT, Underwater Wireless Sensor Networks (UWSNs) have emerged as a promising network system. UWSNs are different from the traditional Territorial Wireless Sensor Networks (TWSNs), and have several unique properties, such as long propagation delay, narrow bandwidth, and low reliability. These unique properties would be great challenges for IoUT. In this paper, we provide a comprehensive study of IoUT, and the main contributions of this paper are threefold: (1) we introduce and classify the practical underwater applications that can highlight the importance of IoUT; (2) we point out the differences between UWSNs and traditional TWSNs, and these differences are the main challenges for IoUT; and (3) we investigate and evaluate the channel models, which are the technical core for designing reliable communication protocols on IoUT.

Tetrahydropyran- and tetrahydrofuran-containing diarylheptanoids from Hedychium coronarium rhizomes.

Seven new diarylheptanoids (1-7) were isolated from the n-BuOH-soluble fraction of the rhizome of Hedychium coronarium. Hedycoropyrans A-C (1-3) contain a tetrahydropyran moiety, while hedycorofurans A-D (4-7) contain a tetrahydrofuran moiety, belonging to a rare structural class of diarylheptanoids. Their structures including stereochemistry were elucidated on the basis of 1D and 2D NMR and ECD spectroscopic analyses and HRESIMS data of the parent compounds and the isopropylidene derivatives of 4 and 7.

Polyvinyl Butyral Polymeric Host Material-Based Fluorescent Thin Films to Achieve Highly Efficient Red and Green Colour Conversion for Advanced Next-Generation Displays.

Rare-earth element-free fluorescent materials are eco-friendlier than other traditional fluorescent precursors, such as quantum dots and phosphors. In this study, we explore a simple and facile solution-based technique to prepare fluorescent films, which are highly stable under ordinary room conditions and show hydrophobic behaviour. The proposed hybrid material was designed with hybrid composites that use polyvinyl butyral (PVB) as a host doped with organic dyes. The red and green fluorescent films exhibited quantum yields of 89% and 80%, respectively, and both are very uniform in thickness and water resistant. Additionally, PVB was further compared with another polymeric host, such as polyvinylpyrrolidone (PVP), to evaluate their binding ability and encapsulation behaviour. Next, the effect of PVB on the optical and chemical properties of the fluorescent materials was studied using UV spectroscopy and Fourier transform infrared spectroscopy. The analysis revealed that no new bond was formed between the host material and fluorescent precursor during the process, with intermolecular forces being present between different molecules. Moreover, the thickness of the fluorescent film and quantum yield relation were evaluated. Finally, the hydrophobic nature, strong binding ability, and optical enhancement by PVB provide a powerful tool for fabricating a highly efficient fluorescent film with enhanced stability in an external environment based on its promising encapsulation properties. These efficient fluorescent films have a bright potential in colour conversion for next-generation display applications.

Prediction of zebrafish embryonic developmental toxicity by integrating omics with adverse outcome pathway.

New approach methodologies (NAMs), especially omics-based high-throughput bioassays have been developed rapidly, providing rich mechanistic information such as molecular initiation events (MIEs) and (sub)cellular key events (KEs) in adverse outcome pathways (AOPs). However, how to apply the knowledge of MIEs/KEs to predict adverse outcomes (AOs) induced by chemicals represents a new challenge for computational toxicology. Here, an integrated method named ScoreAOP was developed and evaluated to predict chemicals' developmental toxicity for zebrafish embryos by integrating four related AOPs and dose-dependent reduced zebrafish transcriptome (RZT). The rules of ScoreAOP included 1) sensitivity of responsive KEs demonstrated by point of departure of KEs (PODKE), 2) evidence reliability and 3) distance between KEs and AOs. Moreover, eleven chemicals with different modes of action (MoAs) were tested to evaluate ScoreAOP. Results showed that eight of the eleven chemicals caused developmental toxicity at tested concentration in apical tests. All the tested chemicals' developmental defects were predicted using ScoreAOP, whereas eight out of the eleven chemicals predicted by ScoreMIE which was developed to score MIEs disturbed by chemicals based on in vitro bioassays data. Finally, in terms of mechanism explanation, ScoreAOP clustered chemicals with different MoAs while ScoreMIE failed, and ScoreAOP revealed the activation of aryl hydrocarbon receptor (AhR) plays a significant role in dysfunction of cardiovascular system, resulting in zebrafish developmental defects and mortality. In conclusion, ScoreAOP represents a promising approach to apply mechanism information obtained from omics to predict AOs induced by chemicals.