Development of a Safe and Effective Bacillus thuringiensis-Based Nanobiopesticide for Controlling Tea Pests.

Mg(OH)2 was used as the nanocarrier of the Bacillus thuringiensis (Bt) Cry1Ac protein, and the synthesized Cry1Ac-Mg(OH)2 composites were regular and uniform nanosheets. Nano-Mg(OH)2 could effectively improve the insecticidal effect of the Cry1Ac protein toward Ectropis obliqua. It could enhance the damage degree of the Cry1Ac protein to intestinal epithelial cells and microvilli, induce and enrich the production of reactive oxygen species (ROS) in the midgut, and enhance the degradation of the Cry1Ac protein into active fragments. Furthermore, an anti-rinsing assay showed that the Cry1Ac-Mg(OH)2 composites were bound to the notch structure of the tea leaf surface. The retention of the Cry1Ac protein increased by 11.45%, and sprayed nano-Mg(OH)2 was rapidly absorbed by different tissues of tea plants. Moreover, nano-Mg(OH)2 and composites did not significantly affect non-target organisms. These results show that nano-Mg(OH)2 can serve as a safe and effective biopesticide carrier, which provides a new approach for stable and efficient Bt preparation.

Integrated analysis of microRNA and messenger RNA expression profiles reveals functional microRNA in infectious bovine rhinotracheitis virus-induced mitochondrial damage in Madin-Darby bovine kidney cells.

BACKGROUND: Studies have confirmed that Infectious bovine rhinotracheitis virus (IBRV) infection induces mitochondrial damage. MicroRNAs (miRNAs) are a class of noncoding RNA molecules, which are involved in various biological processes and pathological changes associated with mitochondrial damage. It is currently unclear whether miRNAs participate in IBRV-induced mitochondrial damage in Madin-Darby bovine kidney (MDBK) cells. RESULTS: In the present study, we used high-throughput sequencing technology, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to screen for mitochondria-related miRNAs and messenger RNAs (mRNAs). In total, 279 differentially expressed miRNAs and 832 differentially expressed mRNAs were identified in 6 hours (IBRV1) versus 24 hours (IBRV2) after IBRV infection in MDBK cells. GO and KEGG enrichment analysis revealed that 42 differentially expressed mRNAs and 348 target genes of differentially expressed miRNAs were correlated with mitochondrial damage, and the miRNA-mitochondria-related target genes regulatory network was constructed to elucidate their potential regulatory relationships. Among the 10 differentially expressed miRNAs, 8 showed expression patterns consistent with the high-throughput sequencing results. Functional validation results showed that overexpression of miR-10a and miR-182 aggravated mitochondrial damage, while inhibition of miR-10a and miR-182 alleviated mitochondrial damage. CONCLUSIONS: This study not only revealed the expression changes of miRNAs and mRNAs in IBRV-infected MDBK cells, but also revealed possible biological regulatory relationship between them. MiR-10a and miR-182 may have the potential to be developed as biomarkers for the diagnosis and treatment of IBRV. Together, Together, these data and analyses provide additional insights into the roles of miRNA and mRNA in IBRV-induced mitochondria damage.

Detection and analysis of hyaluronic acid raw materials from different sources by NIR and aquaphotomics.

Hyaluronic acid (HA), a polysaccharide, is widely used for its essential physiological functions. Although the structures of low molecular weight HA produced by both acid and enzyme degradation methods are extremely similar, there are still differences due to the different degradation principles. There is currently no clear way to distinguish between HA prepared by acidolysis and enzymatic hydrolysis. Based on near-infrared (NIR) spectroscopy and aquaphotomics technology, a method for distinguishing HA raw materials and their mixtures from different sources was proposed, and HA with different mixed ratios was accurately quantified. First, NIR spectra of the HA samples were collected. The spectra were then preprocessed to improve the spectral resolution. Spectral information was extracted based on wavelet transform and principal component analysis, resulting in a final selection of 12 characteristic wavelengths containing classification information. The discriminative and quantitative models were then constructed using the 12 wavelengths. The discriminative model achieved a 100% identification rate for HA from different sources. The correlation coefficient of calibration (Rc), validation (Rp), external test (Rt), root mean square error of cross validation (RMSECV), calibration (RMSEC), validation (RMSEP), and external test (RMSET) of the mixed proportion quantitative model were 0.9876, 0.9876, 0.9898, 0.0546, 0.0433, 0.0440, and 0.0347, respectively. In this study, the problem of structural similarity and non-identifiability of HA produced by acidolysis and enzymatic hydrolysis was addressed, and quality monitoring of HA feedstock in HA circulating links was achieved. This is the first time to achieve accurate quantification of solid mixtures using the aquaphotomics method.

Applications of Probiotic Constituents in Cosmetics.

Over the past few decades, research on the benefits of beneficial microorganisms on skin health has expanded and attracted a lot of attention. Today, a wide range of probiotic products are becoming available. With their extensive component profiles and varied physiological effects, probiotics, as well as extracts of them, have a significant impact on cosmetics. However, the present boom in consumer interest in alternatives has broadened the probiotic industry's research and development frontiers. Considering the foregoing, it should come as no surprise that probiotics are highly valued for their proven anti-aging, skin whitening, anti-inflammatory, and photoprotective effects. This review aims to compile information on probiotics' properties, their extracts, and preparations used in cosmetics. It also further summarizes research and applications on probiotic fermentation to promote the use of probiotic fermentation products in cosmetics. Notably, this review also adds information on particular properties and mechanisms of action of probiotics, which fills a gap in the research and application of probiotics in skin treatment and care. Their antioxidant and anti-aging qualities have received particular consideration. This review provides a new basis for the broad application of probiotics in cosmetics.

Novel ß1,4 N-acetylglucosaminyltransferase in de novo enzymatic synthesis of hyaluronic acid oligosaccharides.

The efficiency of de novo synthesis of hyaluronic acid (HA) using Pasteurella multocida hyaluronate synthase (PmHAS) is limited by its low catalytic activity during the initial reaction steps when monosaccharides are the acceptor substrates. In this study, we identified and characterized a ß-1,4-N-acetylglucosaminyl-transferase (EcGnT) derived from the O-antigen gene synthesis cluster of Escherichia coli O8:K48:H9. Recombinant ß1,4 EcGnT effectively catalyzed the production of HA disaccharides when the glucuronic acid monosaccharide derivative 4-nitrophenyl-ß-D-glucuronide (GlcA-pNP) was used as the acceptor. Compared with PmHAS, ß1,4 EcGnT exhibited superior N-acetylglucosamine transfer activity (~ 12-fold) with GlcA-pNP as the acceptor, making it a better option for the initial step of de novo HA oligosaccharide synthesis. We then developed a biocatalytic approach for size-controlled HA oligosaccharide synthesis using the disaccharide produced by ß1,4 EcGnT as a starting material, followed by stepwise PmHAS-catalyzed synthesis of longer oligosaccharides. Using this approach, we produced a series of HA chains of up to 10 sugar monomers. Overall, our study identifies a novel bacterial ß1,4 N-acetylglucosaminyltransferase and establishes a more efficient process for HA oligosaccharide synthesis that enables size-controlled production of HA oligosaccharides. KEY POINTS: • A novel ß-1,4-N-acetylglucosaminyl-transferase (EcGnT) from E. coli O8:K48:H9. • EcGnT is superior to PmHAS for enabling de novo HA oligosaccharide synthesis. • Size-controlled HA oligosaccharide synthesis relay using EcGnT and PmHAS.

Skin antiaging effects of a multiple mechanisms hyaluronan complex.

OBJECTIVE: Intrinsic skin aging is an inevitable process with reduced extracellular matrix deposition and impaired mechanical integrity in the dermal-epidermal junction (DEJ). Hyaluronan is one of the most promising natural ingredients. In this research, multiple mechanisms of a novel hyaluronan complex against intrinsic skin aging were revealed. METHOD: Immunohistochemical analysis and enzyme-linked immunosorbent assay were employed to evaluate the effect of low-molecular weight sodium hyaluronan, its acetylated derivative and HA complex on expression of matrix metalloproteinase-1 (MMP-1) and type I collagen in normal human fibroblasts. Then, immunohistochemical analysis and hematoxylin and eosin staining was carried out to evaluate identical effects of HA complex in reconstructed skin equivalents, as well as its benefits on histological structure and DEJ. RESULT: In normal human dermal fibroblasts, the hyaluronan complex, which contains low-molecular weight sodium hyaluronate and its acetylated derivative, has synergistic effects by increasing type I collagen expression. At the same time, MMP-1 production was inhibited. This was confirmed in subsequent experiments with skin equivalent, and intriguingly, the hyaluronan complex was also found to increase the expression of two DEJ proteins. CONCLUSION: The multimechanism hyaluronan complex in this proof-of-concept study exhibited skin antiaging effects in vitro through inhibiting the expression of MMP-1 and enhancing type I collagen accumulation and the expression of DEJ proteins, which reveals new avenues for investigating more biological activities of various types of hyaluronan.

BDE-47 Causes Depression-like Effects in Zebrafish Larvae via a Non-Image-Forming Visual Mechanism.

Depression is a high-incidence mood disorder that is frequently accompanied by sleep disturbances, which can be triggered by the non-image-forming (NIF) visual system. Therefore, we hypothesize that polybrominated diphenyl ethers are known to induce visual impairment that could promote depression by disrupting the NIF visual pathway. In this study, zebrafish larvae were exposed to BDE-47 at environmentally relevant concentrations (2.5 and 25 µg/L). BDE-47 caused melanopsin genes that dominate the NIF visual system that fell at night (p < 0.05) but rose in the morning (p < 0.05). Such bidirectional difference transmitted to clock genes and neuropeptides in the suprachiasmatic nucleus and impacted the adjacent serotonin system. However, indicative factors of depression, including serta, htr1aa, and aanat2, were unidirectionally increased 1.3- to 1.6-fold (p < 0.05). They were consistent with the increase in nighttime thigmotaxis (p < 0.05) and circadian hypoactivity (p < 0.05). The results of melanopsin antagonism also indicated that these consequences were possibly due to the combination of direct photoentrainment by melanopsin and circadian disruption originating from melanopsin. Collectively, our findings revealed that BDE-47 exposure disrupted the NIF visual pathway and resulted in depression-like effects, which may further exert profound health effects like mood disorders.

Hyaluronic acid and HA-modified cationic liposomes for promoting skin penetration and retention.

Hyaluronic acid (HA) has been widely used in cosmetics and topical preparations owing to its favorable moisturizing property and potential in enhancing drugs' skin permeability. Here, the influencing factors and underlying mechanism of HA on skin penetration were carefully investigated, and HA-modified Undecylenoyl-Phenylalanine (UP) liposomes (HA-UP-LPs) were designed as a proof of principle for efficacious transdermal drug delivery strategy to enhance the skin penetration and retention. An in vitro penetration test (IVPT) of HA with different molecular weights showed that low molecular weight HA (LMW-HA, 5 kDa and 8 kDa) could pass through the stratum corneum (SC) barrier and enter into the epidermis and dermis layers, whereas its high molecular counterparts (HMW-HA) were trapped on the SC surface. Mechanistic studies revealed that LMW-HA could interact with keratin and lipid in the SC meanwhile exerted a substantial skin hydration effect, which may partially contribute to the SC penetration benefit. In addition, the surface decoration of HA drove an energy-dependent caveolae/lipid raft-mediated endocytosis of the liposomes through direct binding to the CD44 receptors widely expressed on skin cell membranes. Notably, IVPT showed a 1.36-fold and 4.86-fold increase in skin retention of UP and a 1.62-fold and 5.41-fold increase in skin penetration of UP with HA-UP-LPs over UP-LPs and free UP at 24 h, respectively. As a result, the anionic HA-UP-LPs (-30.0 mV) showed enhanced drug skin penetration and retention compared with conventional cationic bared UP-LPs (+21.3 mV) on both in vitro mini-pig skin as well as in vivo mouse skin. Overall, the usage of LMW-HA might offer opportunities in developing novel topical preparations and skin care products with improved transdermal penetration and retention.

The crosstalk effects of polybrominated diphenyl ethers on the retinoic acid and thyroid hormone signaling pathway.

The toxicological and pathological influences of polybrominated diphenyl ethers (PBDEs) on the animal central nervous system have attracted worldwide attention. However, their mechanism of action has not been completely elucidated. Given that retinoic acid (RA) and thyroid hormone (TH) signaling pathway are closely related to neurodevelopment, the crosstalk between the two signaling pathways at the levels of metabolite conversion, gene expression and ligand-receptor interaction after exposure to two representative PBDE congeners (BDE-47 and BDE-209) using zebrafish larvae, dual reporter gene assay, and docking simulation was studied. Our results clarified that BDE-47 could disrupt the transport and metabolism of retinoids, induce changes in expression of key genes, bind with the seven nuclear receptors, and activate RA signaling pathway. BDE-47 exhibited more effects on the indicators of the two signaling pathways than BDE-209. Furthermore, BDE-47 may disrupt TH signaling pathway by disrupting RA signaling pathway, indicating that RA signal is priorly influenced than TH signal. This work offered a new perspective to elucidate TH signal disruption mechanism induced by PBDEs from RA signaling pathway, which is of great significance to elucidate the health effects of PBDEs.

Imaging of Escherichia coli K5 and glycosaminoglycan precursors via targeted metabolic labeling of capsular polysaccharides in bacteria.

The introduction of unnatural chemical moieties into glycosaminoglycans (GAGs) has enormous potential to facilitate studies of the mechanism and application of these critical, widespread molecules. Unnatural N-acetylhexosamine analogs were metabolically incorporated into the capsule polysaccharides of Escherichia coli and Bacillus subtilis via bacterial metabolism. Targeted metabolic labeled hyaluronan and the precursors of heparin and chondroitin sulfate were obtained. The azido-labeled polysaccharides (purified or in capsules) were reacted with dyes, via bioorthogonal chemistry, to enable detection and imaging. Site-specific introduction of fluorophores directly onto cell surfaces affords another choice for observing and quantifying bacteria in vivo and in vitro. Furthermore, azido-polysaccharides retain similar biological properties to their natural analogs, and reliable and predictable introduction of functionalities, such as fluorophores, onto azido-N-hexosamines in the disaccharide repeat units provides chemical tools for imaging and metabolic analysis of GAGs in vivo and in vitro.

Mesoporous Silica Nanoparticles Induce Intracellular Peroxidation Damage of Phytophthora infestans: A New Type of Green Fungicide for Late Blight Control.

Nanopesticides are considered to be a promising alternative strategy for enhancing bioactivity and delaying the development of pathogen resistance to pesticides. Here, a new type of nanosilica fungicide was proposed and demonstrated to control late blight by inducing intracellular peroxidation damage to Phytophthora infestans, the pathogen associated with potato late blight. Results indicated that the structural features of different silica nanoparticles were largely responsible for their antimicrobial activities. Mesoporous silica nanoparticles (MSNs) exhibited the highest antimicrobial activity with a 98.02% inhibition rate of P. infestans, causing oxidative stress responses and cell structure damage in P. infestans. For the first time, MSNs were found to selectively induce spontaneous excess production of intracellular reactive oxygen species in pathogenic cells, including hydroxyl radicals (•OH), superoxide radicals (•O2-), and singlet oxygen (1O2), leading to peroxidation damage in P. infestans. The effectiveness of MSNs was further tested in the pot experiments as well as leaf and tuber infection, and successful control of potato late blight was achieved with high plant compatibility and safety. This work provides new insights into the antimicrobial mechanism of nanosilica and highlights the use of nanoparticles for controlling late blight with green and highly efficient nanofungicides.

In-depth characterization of 1,4-butanediol diglycidyl ether substituted hyaluronic acid hydrogels.

BDDE substituted HA hydrogels remain the most commonly used HA product in the biomedical field. The physical and biochemical properties of the hydrogels are dependent on the degree of modification and substitution patterns/positions, thus, characterizing their fine structure is of great importance for quality assurance. In this study, we developed novel LC-MS methods for accurate determination of MoD as well as in-depth characterization of the linkage network. Fragments resulted from enzymatic depolymerization were resolved by a porous graphitic carbon column followed by online tandem-MS for determining the modification site/residue. With high-resolution separation, two types of previously unknown structures were detected in the cross-linked fragments of 2-B-2 and 4-B-2. Based on the feature of resistance to NaBH4 reduction, these structures contain a GlcNAc residue modified at OH1. This special sugar unit likely derived from reducing end of the native polysaccharide could be a signature to discriminate subtle batch to batch variations.

Structural Analysis and Classification of Low-Molecular-Weight Hyaluronic Acid by Near-Infrared Spectroscopy: A Comparison between Traditional Machine Learning and Deep Learning.

Confusing low-molecular-weight hyaluronic acid (LMWHA) from acid degradation and enzymatic hydrolysis (named LMWHA-A and LMWHA-E, respectively) will lead to health hazards and commercial risks. The purpose of this work is to analyze the structural differences between LMWHA-A and LMWHA-E, and then achieve a fast and accurate classification based on near-infrared (NIR) spectroscopy and machine learning. First, we combined nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR) spectroscopy, two-dimensional correlated NIR spectroscopy (2DCOS), and aquaphotomics to analyze the structural differences between LMWHA-A and LMWHA-E. Second, we compared the dimensionality reduction methods including principal component analysis (PCA), kernel PCA (KPCA), and t-distributed stochastic neighbor embedding (t-SNE). Finally, the differences in classification effect of traditional machine learning methods including partial least squares-discriminant analysis (PLS-DA), support vector classification (SVC), and random forest (RF) as well as deep learning methods including one-dimensional convolutional neural network (1D-CNN) and long short-term memory (LSTM) were compared. The results showed that genetic algorithm (GA)-SVC and RF were the best performers in traditional machine learning, but their highest accuracy in the test dataset was 90%, while the accuracy of 1D-CNN and LSTM models in the training dataset and test dataset classification was 100%. The results of this study show that compared with traditional machine learning, the deep learning models were better for the classification of LMWHA-A and LMWHA-E. Our research provides a new methodological reference for the rapid and accurate classification of biological macromolecules.

Sex-dependent obesogenic effect of tetracycline on Drosophila melanogaster deteriorated by dysrhythmia.

Antibiotics have been identified as obesogens contributing to the prevalence of obesity. Moreover, their environmental toxicity shows sex dependence, which might also explain the sex-dependent obesity observed. Yet, the direct evidence for such a connection and the underlying mechanisms remain to be explored. In this study, the effects of tetracycline, which is a representative antibiotic found in both environmental and food samples, on Drosophila melanogaster were studied with consideration of both sex and circadian rhythms (represented by the eclosion rhythm). Results showed that in morning-eclosed adults, tetracycline significantly stimulated the body weight of females (AM females) at 0.1, 1.0, 10.0 and 100.0 µg/L, while tetracycline only stimulated the body weight of males (AM males) at 1.0 µg/L. In the afternoon-eclosed adults, tetracycline significantly stimulated the body weight of females (PM females) at 0.1, 1.0 and 100.0 µg/L, while it showed more significant stimulation in males (PM males) at all concentrations. Notably, the stimulation levels were the greatest in PM males among all the adults. The results showed the clear sex dependence of the obesogenic effects, which was diminished by dysrhythmia. Further biochemical assays and clustering analysis suggested that the sex- and rhythm-dependent obesogenic effects resulted from the bias toward lipogenesis against lipolysis. Moreover, they were closely related to the preference for the energy storage forms of lactate and glucose and also to the presence of excessive insulin, with the involvement of glucolipid metabolism. Such relationships indicated potential bridges between the obesogenic effects of pollutants and other diseases, e.g., cancer and diabetes.

Effects of carbamazepine on gut microbiota, ARGs and intestinal health in zebrafish.

Carbamazepine (CBZ) in the aquatic environment is recognized as a potential threat to aquatic organisms and public health. However, the response of organism intestinal health, resistome, microbiota, and their relationship after CBZ exposure has been rarely reported. This study aimed to explore the impacts of CBZ on gut microbiota, antibiotic resistance genes (ARGs) and the expression of intestinal health related genes as well as their interaction using the zebrafish model. 16 S ribosomal RNA sequencing indicated CBZ altered the composition of gut microbiota. Using high-throughput quantitative polymerase chain reaction (HT-qPCR), we found the number and abundance of ARGs were impacted by CBZ levels and exposure duration. We also observed the upregulated expression of the pro-inflammatory gene IL6 and downregulated expression of toll-like receptor gene TLR2 and intestinal barrier gene TJP2a at different exposure times. Correlation analyses revealed that Geobacillus, Rhodococcus, Ralstonia, Delftia, Luteolibacter and Escherichia-Shigella might be the main bacterial genera carrying ARGs. Meanwhile, Cetobacterium and Aeromonas could be the dominant bacteria affecting intestinal health related genes. Our results could contribute to understanding the health risks of CBZ to the intestinal microecology of aquatic animals.

Improving the Mechanical Properties of Damaged Hair Using Low-Molecular Weight Hyaluronate.

Chemical treatments of hair such as dyeing, perming and bleaching could cause mechanical damage to the hair, which weakens the hair fibers and makes the hair break more easily. In this work, hyaluronate (HA) with different molecular weight (MW) was investigated for its effects on restoring the mechanical properties of damaged hair. It was found that low-MW HA (average MW~42 k) could significantly improve the mechanical properties, specifically the elastic modulus, of overbleached hair. The fluorescent-labeling experiments verified that the low-MW HA was able to penetrate into the cortex of the hair fiber, while high-MW HA was hindered. Fourier transform infrared spectrometry (FT-IR) results implied the formation of additional intermolecular hydrogen bonds in the HA-treated hair. Thermos gravimetric analysis (TGA) indicated that the HA-treated hair exhibited decreased content of loosely bonded water, and differential scanning calorimetry (DSC) characterizations suggested stronger water bonding inside the HA-treated hair, which could alleviate the weakening effect of loosely bonded water on the hydrogen bond networks within keratin. Therefore, the improved elastic modulus and mechanical strength of the HA-treated hair could be attributed to the enhanced formation of hydrogen bond networks within keratin. This study illustrates the capability of low-MW HA in hair damage repair, implying an enormous potential for other moisturizers to be used in hair care products.

Enhanced Stability and Function of Probiotic Streptococcus thermophilus with Self-Encapsulation by Increasing the Biosynthesis of Hyaluronan.

The harsh conditions of the gastrointestinal tract limit the potential health benefits of oral probiotics. It is promising that oral bioavailability is improved by strengthening the self-protection of probiotics. Here, we report the encapsulation of a probiotic strain by endogenous production of hyaluronan to enhance the effects of oral administration of the strain. The traditional probiotic Streptococcus thermophilus was engineered to produce hyaluronan shells by using traceless genetic modifications and clustered regularly interspaced short palindromic repeat interference. After oral delivery to mice in the form of fermented milk, hyaluronan-coated S. thermophilus (204.45 mg/L hyaluronan in the milk) exhibited greater survival and longer colonization time in the gut than the wild-type strain. In particular, the engineered probiotic strain could also produce hyaluronan after intestinal colonization. Importantly, S. thermophilus self-encapsulated with hyaluronan increased the number of goblet cells, mucus production, and abundance of the microorganisms related to the biosynthesis of short-chain fatty acids, resulting in the enhancement of the intestinal barrier. The coating formed by endogenous hyaluronan provides an ideal reference for the effective oral administration of probiotics.

Hyaluronic acid-cyclodextrin encapsulating paeonol for treatment of atopic dermatitis.

The cyclodextrin (CD) was grafted onto hyaluronic acid (HA) to form a topical delivery carrier (HACD) in which Paeonol was loaded in its CD cavity and self-assemble into the polymeric micelles (HACD-PAE) for the treatment of atopic dermatitis. Fluorescence microscope observed that HACD could fast penetrate into the skin and remain stable within 12 h. In vitro penetration test (IVPT) results showed the PAE retentions of HACD-PAE group in the stratum corneum and dermis were 3.35 and 1.78 times improvement than that of PAE group. ATR-FTIR and H&E staining assays indicated HACD could increase the gap of keratinocytes by interacting with corneum lipids and loosening the keratin. Furthermore, HACD-PAE showed the best therapeutic effect on atopic dermatitis mice. Thus HACD could be a promising skin-specific delivery carrier, not only promoting the drug penetrating but increasing its remaining in the skin and play the skin disease therapy and skin-care role.

Glycosaminoglycan-based injectable hydrogels with multi-functions in the alleviation of osteoarthritis.

Osteoarthritis (OA), as an "undead cancer", causes a serious burden for both individuals and society. In this study, a glycosaminoglycan-based injectable hydrogel was prepared with hyaluronic acid (HA), chondroitin sulfate E disaccharide (ΔUA-diSE) and thermosensitive Pluronic F127 (PF127) to provide a new strategy for OA alleviation. Both in vitro and in vivo biological evaluations were introduced to investigate the slow-release capacity, related mechanisms, and effectiveness of PF-HA-diSE on OA. The results demonstrated that PF-HA-diSE could alleviate OA effectively by regulating the complement system, especially the formation of C5b-9, and its downstream signals. Interestingly, we also found that PF127 was not only a drug carrier, but may have the potential on inhibiting C5b-9 formation. Altogether, these findings provided a more effective local drug delivery system for glycosaminoglycans in better treatment of OA and related diseases.

BDE-99 Disrupts the Photoreceptor Patterning of Zebrafish Larvae via Transcription Factor six7.

Proper visual function is essential for collecting environmental information and supporting the decision-making in the central nervous system and is therefore tightly associated with wildlife survival and human health. Polybrominated diphenyl ethers (PBDEs) were reported to impair zebrafish vision development, and thyroid hormone (TH) signaling was suspected as the main contributor. In this study, a pentabrominated PBDE, BDE-99, was chosen to further explore the action mechanism of PBDEs on the disruption of zebrafish color vision. The results showed that BDE-99 could impair multiple photoreceptors in the retina and disturb the behavior guided by the color vision of zebrafish larvae at 120 h post-fertilization. Although the resulting alteration in photoreceptor patterning highly resembled the effects of 3,3',5-triiodo-l-thyroine, introducing the antagonist for TH receptors was unable to fully recover the alteration, which suggested the involvement of other potential regulatory factors. By modulating the expression of six7, a key inducer of middle-wavelength opsins, we demonstrated that six7, not THs, dominated the photoreceptor patterning in the disruption of BDE-99. Our work promoted the understanding of the regulatory role of six7 in the process of photoreceptor patterning and proposed a novel mechanism for the visual toxicity of PBDEs.