Melatonin enhances cotton immunity to Verticillium wilt via manipulating lignin and gossypol biosynthesis.

Plants endure challenging environments in which they are constantly threatened by diverse pathogens. The soil-borne fungus Verticillium dahliae is a devastating pathogen affecting many plant species including cotton, in which it significantly reduces crop yield and fiber quality. Melatonin involvement in plant immunity to pathogens has been reported, but the mechanisms of melatonin-induced plant resistance are unclear. In this study, the role of melatonin in enhancing cotton resistance to V. dahliae was investigated. At the transcriptome level, exogenous melatonin increased the expression of genes in phenylpropanoid, mevalonate (MVA), and gossypol pathways after V. dahliae inoculation. As a result, lignin and gossypol, the products of these metabolic pathways, significantly increased. Silencing the serotonin N-acetyltransferase 1 (GhSNAT1) and caffeic acid O-methyltransferase (GhCOMT) melatonin biosynthesis genes compromised cotton resistance, with reduced lignin and gossypol levels after V. dahliae inoculation. Exogenous melatonin pre-treatment prior to V. dahliae inoculation restored the level of cotton resistance reduced by the above gene silencing effects. Melatonin levels were higher in resistant cotton cultivars than in susceptible cultivars after V. dahliae inoculation. The findings indicate that melatonin affects lignin and gossypol synthesis genes in phenylpropanoid, MVA, and gossypol pathways, thereby enhancing cotton resistance to V. dahliae.

Effects of silver diamine fluoride on dentine carious lesions induced by Streptococcus mutans and Actinomyces naeslundii biofilms.

BACKGROUND. Silver diamine fluoride (SDF) has been shown to be a successful treatment for arresting caries. However, the mechanism of SDF is to be elucidated. AIM. To characterize the effects of SDF on dentine carious induced by Streptococcus mutans and Actinomyces naeslundii. DESIGN. Thirty-two artificially demineralized human dentine blocks were inoculated: 16 with S. mutans and 16 with A. naeslundii. Either SDF or water was applied to eight blocks in each group. Biofilm morphology, microbial kinetics and viability were evaluated by scanning electron microscopy, colony forming units, and confocal microscopy. The crosssection of the dentine carious lesions were assessed by microhardness testing, scanning electron microscopy with energy-dispersive x-ray spectroscopy and Fourier transform infrared spectroscopy. RESULTS. Biofilm counts were reduced in SDF group than control (P < 0.01). Surfaces of carious lesions were harder after SDF application than after water application (P < 0.05), in S. mutans group, Ca and P weight percentage after SDF application than after water application (P < 0.05). Lesions showed a significantly reduced level of matrix to phosphate after SDF treatment (P < 0.05). CONCLUSION. Present study showed that SDF posses an anti-microbial activity against cariogenic biofilm of S. mutans or A. naeslundii formed on dentine surfaces. SDF slowed down demineralization of dentine. This dual activity could be the reason behind clinical success of SDF.

Responsive Multivesicular Polymeric Nanovaccines that Codeliver STING Agonists and Neoantigens for Combination Tumor Immunotherapy.

Immune checkpoint blockade (ICB) has significantly advanced cancer immunotherapy, yet its patient response rates are generally low. Vaccines, including immunostimulant-adjuvanted peptide antigens, can improve ICB. The emerging neoantigens generated by cancer somatic mutations elicit cancer-specific immunity for personalized immunotherapy; the novel cyclic dinucleotide (CDN) adjuvants activate stimulator of interferon genes (STING) for antitumor type I interferon (IFN-I) responses. However, CDN/neoantigen vaccine development has been limited by the poor antigen/adjuvant codelivery. Here, pH-responsive CDN/neoantigen codelivering nanovaccines (NVs) for ICB combination tumor immunotherapy are reported. pH-responsive polymers are synthesized to be self-assembled into multivesicular nanoparticles (NPs) at physiological pH and disassembled at acidic conditions. NPs with high CDN/antigen coloading are selected as NVs for CDN/antigen codelivery to antigen presenting cells (APCs) in immunomodulatory lymph nodes (LNs). In the acidic endosome of APCs, pH-responsive NVs facilitate the vaccine release and escape into cytosol, where CDNs activate STING for IFN-I responses and antigens are presented by major histocompatibility complex (MHC) for T-cell priming. In mice, NVs elicit potent antigen-specific CD8+ T-cell responses with immune memory, and reduce multifaceted tumor immunosuppression. In syngeneic murine tumors, NVs show robust ICB combination therapeutic efficacy. Overall, these CDN/neoantigen-codelivering NVs hold the potential for ICB combination tumor immunotherapy.

Ellagic acid solid dispersion: Characterization and bioactivity in the hydroxyl radical oxidation system.

Ellagic acid solid dispersion (EASD) was prepared using polyvinylpyrrolidone (PVP) as a carrier to improve its solubility. The solubility of EASD enhanced to 0.593 mg/mL, more than 20 times of the solubility on pure EA. The structure of EASD was analyzed by UV-visible spectroscopy, Fourier transforms infrared spectrometer (FT-IR) and X-ray diffraction (XRD), and results indicated the successful preparation of EASD, with a decrease in crystallinity. Differential scanning calorimetry (DSC) spectrums showed a lower endothermic peak of EASD than EA. By antioxidant analysis, the EASD with the concentration of 3 mg/mL was used in the protein oxidation analysis in hydroxyl radical oxidation simulation system, which was established by the myofibrillar of hairtail. EASD exhibited an excellent inhibit effect on protein oxidation. By increasing the solubility, EASD broadens the application range of EA, providing a theoretical basis for its application in the preservation of aquatic products.

Effect of Silver Fluoride in Preventing the Formation of Artificial Dentinal Caries Lesions in vitro.

OBJECTIVE: To investigate the effect of silver fluoride in preventing the development of artificial caries lesions in root dentine using an artificial mouth system (AMS). METHODS: A total of 34 extracted intact human premolars were embedded individually in blocks with one root dentine surface exposed. Among these, 32 were randomly divided into four groups (eight each) and the remaining two tooth blocks were used in the baseline evaluation of the cariogenic biofilm after bacterial inoculation. The interventions (topical application of 2.36 M solutions) were applied after inoculation as follows: group-1, silver fluoride (AgF); group-2, potassium fluoride (KF); group-3, silver nitrate (AgNO3); and group-4, deionised water (control). Subsequently, the tooth blocks were transferred into the AMS to start an artificial caries challenge (5% sucrose was delivered three times per day). After 10 days, the formed biofilm was assessed via colony forming unit (CFU) counts, confocal laser scanning microscopy, and scanning electron microscopy. The artificial dentinal caries lesion was evaluated using micro-computed tomography. RESULTS: After the interventions and the 10-day challenge in the AMS, the median CFUs (AgF < AgNO3 < KF = control, P < 0.001) and the median live-to-dead bacteria ratios (AgF < AgNO3 < KF = control, P < 0.005) of the biofilm differentiated significantly among the groups. Scattered bacterial cells were found in the tooth blocks of the AgF and AgNO3 groups, while a confluent biofilm layer was observed in the tooth blocks of the KF and control groups. The median lesion depth in the AgF group was significantly lower than in the AgNO3 (P = 0.016), KF (P = 0.016) and control (P = 0.009) groups. CONCLUSION: The combined use of silver and fluoride ions in the AgF solution significantly protected dentine against the development of caries lesions.

Self-Assembled DNA Immunonanoflowers as Multivalent CpG Nanoagents.

Synthetic unmethylated cytosine-guanine (CpG) oligodeoxynucleotides are immunostimulatory motifs that have shown promise as vaccines or adjuvants for diseases such as cancers and infectious diseases. In the present work, novel immuno-nanoflowers (NFs), self-assembled from long DNA integrated with tandem CpG through rolling circle replication, were developed for efficient CpG delivery and protection from nuclease degradation. In a model of macrophage-like cells, the CpG NFs proved to be potent immunostimulators by triggering the proliferation of these immune cells, which, in turn, secreted immunostimulatory cytokines, including tumor necrosis factor α, interleukin-6, and interleukin-10. These results demonstrate the ability of CpG NFs to induce cancer cell apoptosis and necrosis.

Supramolecular inclusion-based molecular integral rigidity: a feasible strategy for controlling the structural connectivity of uranyl polyrotaxane networks.

The assembly of two-dimensional (2D) large channel uranyl-organic polyrotaxane networks as well as structural regulation of uranyl-bearing units using jointed cucurbit[6]uril-based pseudorotaxanes with integral rigidity based on supramolecular inclusion is presented for the first time. This construction strategy concerning controlling molecular integral rigidity based on supramolecular inclusion may afford an entirely new methodology for coordination chemistry.

[Occluding effects of three new calcium desensitizers on dentinal tubules in vitro].

OBJECTIVE: To evaluate the occluding effects of three new calcium desensitizers on dentinal tubules in vitro. METHODS: Twenty-five dentin specimens of 1.00 mm thick from freshly extracted third molars were divided into five groups randomly. After treatment with 6% citric acid, group A was treated with distilled water, and group B-E were treated with NovaMin, Pro-Argin, casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), and 75% NaF glycerin for 2 min respectively. Then the teeth were vertically cleaved into two sections. The surfaces and cross sections were observed by the scanning electron microscope (SEM) and energy dispersive X-ray (EDX), which were analyzed by the Image-Pro Plus software. RESULTS: The percentage of dentin tubules sealed were (81.6 ± 6.1)%, (71.5 ± 6.3)%, (43.2 ± 2.6)%, (39.9 ± 4.1)% for groups B, C, D and E respectively, and the occluding depth were (30.33 ± 2.26), (24.55 ± 2.58), (16.10 ± 4.65) and (8.90 ± 1.51) µm respectively. The differences between these groups were statistically significant (P < 0.01) except for group B and C (P > 0.05). However, there was no significant difference between all the groups for the Ca/P ratios (P = 0.342). CONCLUSIONS: NovaMin may have better immediate occluding effects than other desensitizers and could deposit a dentin-like mineral.