Asiaticasics A-O, structurally intriguing coumarins from Toddalia asiatica with potential inflammatory inhibitory activity.

Ethyl acetate fraction of Toddalia asiatica was fractionated to yield fifteen previously undescribed prenylated coumarins, asiaticasics A-O (1-15) along with nine (16-24) known derivatives. The structures of these undescribed coumarins were established by spectroscopic analysis and reference data. Biological activity evaluation showed that compound 3 with the IC50 value of 2.830 µM and compound 12 with the IC50 value of 0.682 µM owned anti-inflammatory activity by detecting the rate of lactate dehydrogenase release in pyroptosis J774A.1 cells. The results showed that the expression of Caspase-1 and IL-1ß was decreased in a dose-dependent manner in the compound 12 treatment group, suggesting that compound 12 may reduce pyroptosis by inhibiting NLRP3 inflammasome. To further determine that compound 12 treatment can inhibit macrophage pyroptosis, morphological observation was performed and the results were consistent with the bioactivity evaluation.

Euphopias G - J, macrocyclic diterpenes with anti-zika virus activity from Euphorbia helioscopia L.

Four new diterpenoids (1-4) and sixteen known diterpenoids (5-20) were purified from the whole plant of Euphorbia helioscopia L. Compounds 1 and 2 were rhamofolane diterpenoids with a 5/7/6 tricyclic systems, compound 3 was a lathyranes diterpenoid, and compound 4 was a jathophanes diterpenoid. The isolated compounds were tested for their cytotoxicity and anti-Zika virus properties, and compounds 9 and 15 showed low cytotoxicity and strong anti-Zika virus properties with EC50 2.63 and 5.94 µM, respectively. Further, the inhibitory effects of compounds on protein levels were determined using Western blotting and immunofluorescence assays.

Three new lanostane triterpenoids and two new amides from Alternaria sp. with NLRP3 inflammasome inhibitory activity.

Three new lanostane triterpenoids (1-3) along with two new amides fatty compounds (4-5) were isolated from the ethyl acetate extract of a culture of the endophytic fungus Alternaria sp. gx-2. Their structures were identified by 1D and 2D NMR spectral data and HRESIMS. Compounds 1-12 were evaluated for their anti-inflammatory and tyrosinase inhibition activities. The isolated compounds did not show inhibitory activities at a concentration of 100 µM against tyrosinase, while under the concentration of 10 µM, the release of lactate dehydrogenase (LDH) inhibition rate of compound 1 was 54.45%, indicating that compound 1 had moderate anti-inflammatory activity on the activation of NLRP3 inflammasome.

Chemical constituents from the twigs and leaves of Picrasma quassioides.

Two new compounds, including a norsesquiterpenoid, annuionone H (1), and a quassinoid, picraqualide G (2), along with eleven known compounds (3-13), were isolated from the twigs and leaves of Picrasma quassioides. Comprehensive spectroscopic analyses and NMR calculation with DP4+ analysis were used to identify their structures. Moreover, of all these compounds, compound 4 showed a week inhibition rate in the anti-inflammatory screening results against mouse macrophage J774A.1 cell.

Chemical Constituents of the Branches and Leaves of Picrasma chinensis P.Y. Chen and Tyrosinase Inhibiting Activity.

One new alkaloid, picrasine A, two new quassinoids, picralactones A-B, together with eleven known compounds were isolated from Picrasma chinensis P.Y. Chen. The structures of these compounds were determined using 1D and 2D NMR, HR-ESI-MS, and IR spectroscopic data, and by comparison with published data. Some compounds were tested for tyrosinase inhibiting activity, however, none of them exhibited strong inhibitory effects.

Callicarpanes A-L, Twelve New Clerodane Diterpenoids with NLRP3 Inflammasome Inhibitory Activity from Callicarpa integerrima.

Twelve new clerodane diterpenoids named callicarpanes A-L (1-12), together with eight known compounds (13-20), were isolated from Callicarpa integerrima. Their structures were determined by comprehensive spectroscopic data. The calculated chemical shifts were used to identify relative configurations using DP4+ analysis. The absolute configurations (AC) were assigned based on quantum chemical calculations and X-ray single-crystal diffraction methods. Compounds 1, 3, 5, 9, 10, 12, 15, 16, and 19 showed significant inhibitory activity for NLRP3 inflammasome activation, with the IC50 against lactate dehydrogenase (LDH) release ranging from 0.08 to 4.78 µM. Further study revealed that compound 10 repressed IL-1ß secretion and caspase-1 maturation in J774A.1 cell as well as blocked macrophage pyroptosis.

Callintegers A and B, Unusual Tricyclo[4.4.0.09,10]tetradecane Clerodane Diterpenoids from Callicarpa integerrima with Inhibitory Effects on NLRP3 Inflammasome Activation.

Callintegers A (1) and B (2), unprecedented clerodane norditerpenoids based on a novel carbon skeleton, were isolated from Callicarpa integerrima. Compounds 1 and 2 possess a novel 6/6/6-fused tricyclic ring system. Their structures and absolute configurations were determined by quantum chemical calculations, spectroscopic analysis, and single-crystal X-ray diffraction methods. Biological evaluation showed that compound 2 inhibited IL-1ß secretion in a dose-dependent manner with an IC50 value of 5.5 ± 3.2 µM. Caspase-1 maturation and IL-1ß secretion were also reduced, indicating that compound 2 impaired NLRP3 inflammasome activation.

Effects of autotoxicity and allelopathy on seed germination and seedling growth in Medicago truncatula.

Autotoxicity is a form of intraspecific allelopathy, in which a plant species inhibits the establishment or growth of the same species through the release of toxic chemical compounds into the environment. The phenomenon of autotoxicity in crops is best traced in alfalfa (Medicago sativa). A close relative of alfalfa, M. truncatula, has been developed into an excellent model species for leguminous plants. However, it is not known whether M. truncatula has autotoxicity. In this study, M. truncatula root exudates showed a negative impact on the growth of M. truncatula seedlings, indicating autotoxicity. Detailed analyses with plant extracts from M. truncatula and alfalfa revealed varying degrees of suppression effects in the two species. The extracts negatively affected seed germination potential, germination rate, radicle length, hypocotyl length, synthetic allelopathic effect index, plant height, root growth, fresh weight, dry weight, net photosynthetic rate, transpiration rate, and stomatal conductance in both M. truncatula and alfalfa. The results demonstrated that autotoxicity and allelopathic effects exist in M. truncatula. This opens up a new way to use M. truncatula as a model species to carry out in-depth studies of autotoxicity and allelopathy to elucidate biochemical pathways of allelochemicals and molecular networks controlling biosynthesis of the chemicals.

Transcriptome Analysis of Leaf Senescence Regulation Under Alkaline Stress in Medicago truncatula.

In plants, the leaf is an essential photosynthetic organ, and is the primary harvest in forage crops such as alfalfa (Medicago sativa). Premature leaf senescence caused by environmental stress can result in significant yield loss and quality reduction. Therefore, the stay-green trait is important for improving the economic value of forage crops. Alkaline stress can severely damage leaf cells and, consequently, cause leaf senescence. To understand the molecular regulatory mechanisms and identify vital senescence-associated genes under alkaline stress, we used high-throughput sequencing to study transcriptional changes in Medicago truncatula, a model plant for forage crops. We identified 2,165 differentially expressed genes, 985 of which were identical to those in the dark-induced leaf senescence group. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that the 985 genes were mainly enriched in nutrient cycling processes such as cellular amino acid metabolic processes and organic substance catabolic processes, indicating nutrient redistribution. The other 1,180 differentially expressed genes were significantly enriched in the oxidoreductase complex, aerobic respiration, and ion transport. Our analysis showed the two gene sets guiding the coupled physiological and biochemical alterations play different roles under alkaline stress with a coordinated and integrated way. Many transcription factor families were identified from these differentially expressed genes, including MYB, WRKY, bHLH, and NAC which have particular preference involved in stress resistance and regulation of senescence. Our results contribute to the exploration of the molecular regulatory mechanisms of leaf senescence in M. truncatula under alkaline stress and provide new candidate genes for future breeding to improve the biomass and quality of forage crops.

The role of ICOS in allergic disease: Positive or Negative?

With the rapid increase in the incidence of allergic diseases, the mechanisms underlying the development of these diseases have received a great deal of attention, and this is particularly true in regard to the role of ICOS in allergic diseases. Current studies have revealed that ICOS affects the functional activity of multiple immune cells that modulate the adaptive immune system. Additionally, ICOS also plays a crucial role in mediating cellular immunity and coordinating the response of the entire immune system, and thus, it plays a role in allergic reactions. However, the ICOS/ICOS-ligand (ICOS-L) axis functions in a dual role during the development of multiple allergic diseases. In this review, we explore the role of ICOS/ICOSL in the context of different immune cells that function in allergic diseases, and we summarize recent advances in their contribution to these diseases.

Complementary sample preparation strategies (PVD/BEXP) combining with multifunctional SPM for the characterizations of battery interfacial properties.

The cathode/anode-electrolyte interfaces in lithium/sodium ion batteries act as the "gate" for the ion exchange between the solid electrode and liquid electrolyte. Understanding the interfacial properties of these solid-liquid interfaces is essential for better design high-performance lithium/sodium ion batteries. Here, we provide a novel method for studying solid-liquid interfacial properties of battery materials through combining physical vapor deposition (PVD) and beam-exit cross-sectional polishing (BEXP) followed by controlled environment multifunctional Scanning Probe Microscope (SPM). In this method, commercial battery materials can be either directly grown on the current collector substrates, or polished by obliqued Ar-ion beams to get a nanoscale flat surface which allows the multifunctional SPM to study sample directly in the liquid electrolyte or in protective oxygen/H2O free environment. This approach allows to investigate wide range of interfacial properties, including surface morphology, internal cracks, mechanical properties, electronic/ionic conductivity and surface potential, with nanoscale resolution in-operando during the battery cycles as well as post-mortem.•PVD and novel BEXP methods were introduced to prepare battery powder materials as perfect specimens for nanoscale SPM characterization.•Various physical/chemical properties of battery materials can be probed on the as-prepared specimens under liquid electrolyte using in situ/operando SPM techniques.•Ex situ/post-mortem analyses based on the controlled environment multifunction SPM characterizations can be achieved in the BEXP polished degradation battery electrodes.

Bacteroides thetaiotaomicron Ameliorates Experimental Allergic Airway Inflammation via Activation of ICOS+Tregs and Inhibition of Th2 Response.

Inhibition of allergic airway diseases (AAD) by immunomodulation of the adaptive immune system through restoration of the enteric dysbiosis is an emerging therapeutic strategy. Patients with allergic rhinitis (n = 6) and healthy controls (n = 6) were enrolled, and gut microbiome composition analysis was performed by 16S rDNA sequencing. We also established an ovalbumin (OVA)-induced allergic airway inflammation murine model. Dysbiosis of the gut flora was observed in both AAD patients and the mice, with the decrease of the biodiversity and the quantity of the Bacteroidetes phylum. Oral application of Bacteroides (B.) thetaiotaomicron ameliorated the symptoms of OVA-induced airway hyperresponsiveness (AHR) and attenuated the airway inflammation in mice. In addition, nasal lavage fluid (NALF) and bronchoalveolar lavage fluid (BALF) from AAD mice orally administered with B. thetaiotaomicron showed reduced numbers of immune cells, and diminished secretion of T helper (Th)-2 cytokines (IL-4, IL-5, and IL-13) compared with the corresponding control mice, whereas the levels of Th1 cytokineIFN-γ was not changed in both the groups. When B. thetaiotaomicron was co-administered with metronidazole in AAD mice, the immunomodulatory effect was weakened and the allergic inflammatory response was aggravated. The ratios of CD4+Foxp3+ cells, CD4+ICOS+ T cells, CD4+ICOS+ Foxp3+ regulatory T cells, and IL-10-expressing CD4+Foxp3+ cells were increased in lymphocytes of spleen, mesenteric, and cervical lymph nodes of AAD mice administrated with B. thetaiotaomicron. Therefore, our data indicate that oral administration of B. thetaiotaomicron effectively inhibited the development of AAD in murine model; inhibition was mediated by the activation of Tregs and inhibition of Th2 response without promoting a Th1 response.

Comprehensive analysis of coding sequence architecture features and gene expression in Arachis duranensis.

Coding sequence (CDS) architecture affects gene expression levels in organisms. Codon optimization can increase the gene expression level. Therefore, understanding codon usage patterns has important implications for research on genetic engineering and exogenous gene expression. To date, the codon usage patterns of many model plants have been analyzed. However, the relationship between CDS architecture and gene expression in Arachis duranensis remains poorly understood. According to the results of genome sequencing, A. duranensis has many resistant genes that can be used to improve the cultivated peanut. In this study, bioinformatic approaches were used to estimate A. duranensis CDS architectures, including frequency of the optimal codon (Fop), polypeptide length and GC contents at the first (GC1), second (GC2) and third (GC3) codon positions. In addition, Arachis RNA-seq datasets were downloaded from PeanutBase. The relationships between gene expression and CDS architecture were assessed both under normal growth as well as nematode and drought stress conditions. A total of 26 codons with high frequency were identified, which preferentially ended with A or T in A. duranensis CDSs under the above-mentioned three conditions. A similar CDS architecture was found in differentially expressed genes (DEGs) under nematode and drought stresses. The GC1 content differed between DEGs and non-differentially expressed genes (NDEGs) under both drought and nematode stresses. The expression levels of DEGs were affected by different CDS architectures compared with NDEGs under drought stress. In addition, no correlation was found between differential gene expression and CDS architecture neither under nematode nor under drought stress. These results aid the understanding of gene expression in A. duranensis.

Cryptotanshinone Attenuates Ischemia/Reperfusion-induced Apoptosis in Myocardium by Upregulating MAPK3.

ABSTRACT: Chinese people have used the root of Salvia miltiorrhiza Bunge (called "Danshen" in Chinese) for centuries as an anticancer agent, anti-inflammatory agent, antioxidant, and cardiovascular disease drug. In addition, Danshen is considered to be a drug that can improve ischemia/reperfusion (I/R)-induced myocardium injury in traditional Chinese medicine. However, Danshen is a mixture that includes various bioactive substances. In this study, we aimed to identify the protective component and mechanism of Danshen on myocardium through network pharmacology and molecular simulation methods. First, cryptotanshinone (CTS) was identified as a potential active compound from Danshen that was associated with apoptosis by a network pharmacology approach. Subsequently, biological experiments validated that CTS inhibited ischemia/reperfusion-induced cardiomyocyte apoptosis in vivo and in vitro. Molecular docking techniques were used to screen key target information. Based on the simulative results, MAPKs were verified as well-connected molecules of CTS. Western blotting assays also demonstrated that CTS could enhance MAPK expression. Furthermore, we demonstrated that inhibition of the MAPK pathway reversed the CTS-mediated effect on cardiomyocyte apoptosis. Altogether, our work screened out CTS from Danshen and demonstrated that it protected cardiomyocytes from apoptosis.

[Clinical characteristics and surgical treatment analysis of paranasal ossifying fibroma].

Objective:To analyze the clinical features and discuss the treatment of ossifying fibroma in the nasal cavity and sinuses. Method:The patients were performed surgical treatment after admission. 6 cases were treated by endoscopic transnasal approach with image guidance system to resect the mass, 8 cases were operated by simple endoscopic approach, tumor resection was performed via endoscopic surgery with external approach in 2 cases, and endoscopic surgery combined with modified Caldwell-Luc procedure in 1 case. 1 patient was operated through labiolingual groove approach. Result:The intraoperative blood loss of ossified fibroma patients was large, with an average blood loss of 550ml. All the patients were followed up for 6 months to 8 years, 15 patients with complete resection had no recurrence after surgery, and 3 patients with partial resection survived with tumor. Conclusion:Ossifying fibroma in the nasal cavity and sinuses can be completely resected by nasal endoscopic surgery with less trauma and good effect. Transnasal endoscopic surgery assisted by image navigation system can protect important structures in lesions involving orbital cardboard and anterior skull base. Nasal endoscopic surgery combined with small eyebrow incision approach is feasible for ossifying fibroma invading frontal sinus. Ossifying fibroma, which requires adequate preoperative evaluation and blood preparation is prone to bleeding, and lesions with rich blood supply need preoperative interventional therapy.

Continued development of auditory ability in autism spectrum disorder children: A clinical study on click-evoked auditory brainstem response.

OBJECTIVES: The study aimed to analyze the developmental mode of auditory at the level of brainstem in preschool autistic children using click-evoked auditory brainstem response (click-ABR). METHODS: Twenty children with autism spectrum disorder (ASD) and 20 age matched typical development children (TD) were recruited. The detail data recorded from click-ABR were collected at two time periods (T1 and T2). RESULTS: There was no significant change in TD group at two time periods. In ASD group, wave V latency was significantly shortened at T2 compared to that recorded at T1. The interpeak latency of I-V was short at T2 versus at T1 in the autistic children. Compared to the TD group, ASD was associated with longer latencies for waves V and longer interpeak latencies of I-III, I-V at T1. In addition, ASD group also indicated longer latencies of wave III and wave V, longer interpeak latencies of I-III and I-V at T2 compared to the TD group. CONCLUSIONS: ASD group had immature and dysfunction developmental mode in auditory stimuli perception at the level of brainstem. The performance of auditory ability in children with ASD improved gradually with ages. However, there are still differences compared with TD children.

A High Energy Density Azobenzene/Graphene Oxide Hybrid with Weak Nonbonding Interactions for Solar Thermal Storage.

Incorporating photochromic chromophores into polymer composites provides the possibility of a reversible photoswitch of the intrinsic properties of these materials. In this paper we report a route to attach azobenzene (AZO) moiety covalently to graphene oxide (GO) to create chromophore/graphene oxide (AZO-GO) hybrid, in which GO is both part of the chromophore and the template. Due to the high grafting density of AZO moiety and the low mass of the novel structure, the hybrid is a potential solar thermal storage material with high energy density of about 240 Wh·kg-1. It is found that C-H···π interaction between the cis-AZO chromophores and the aromatic rings of the substrate induces collective electronic modifications of GO at critical percentage of cis-isomers and reduce the thermal barrier of π-π* transition of the chromophores directly, which results in two sections of first-order reactions during the photoisomerization of trans- to cis-hybrid and also thermally stabilizes the cis-hybrid. Our findings demonstrate that high-performance AZO-GO hybrid can be manipulated by optimizing intermolecular nonbonding interactions.

Organized Hematoma: An Analysis of 84 Cases with Emphasis on Difficult Prediction and Favorable Management.

OBJECTIVE: To characterize features of organized hematoma (OH) that may cause considerable diagnostic difficulties. STUDY DESIGN: Case series with chart review. SETTING: Tertiary medical center. SUBJECTS AND METHODS: Eighty-four patients with pathologically confirmed OH over a 10-year period were retrospectively reviewed for clinical features, imaging findings, pathologic characteristics, and treatment modalities. RESULTS: This study included 39 males and 45 females who presented with frequent epistaxis and nasal obstruction. There were 62 (74%) patients >40 years old (mean, 50; range, 9-81). OH mainly originated in the maxillary sinus (n = 82) or nasal cavity (n = 2) unilaterally, and most were expansile masses (n = 73) that extended into nasal cavity (n = 71) or choanae (n = 17). Several lesions were locally aggressive and simulated a malignant process that involved the ethmoid sinus (n = 22), orbit (n = 11), pterygopalatine fossa (n = 16), infratemporal fossa (n = 9), cheek (n = 3), and hard palate (n = 3). Internal architecture on computed tomography (CT) scans showed OH with expansile remodeling of the maxillary wall (82.1%) and smooth bony destruction (70.2%), whereas T2-weighted magnetic resonance (MR) images showed inhomogeneity with a notable hypointense peripheral rim in all lesions. CT and MR contrast-enhanced images revealed patchy heterogeneous enhancement that could be interpreted according to histopathologic findings of hemorrhage and neovascularization. OH was successfully removed with endoscopic surgery, although 5 cases recurred. CONCLUSIONS: OH can be successfully treated by endoscopic surgery. CT and MR examination provide characteristic findings for prediction and careful surgical planning.

Dietary Fiber Intake Regulates Intestinal Microflora and Inhibits Ovalbumin-Induced Allergic Airway Inflammation in a Mouse Model.

BACKGROUND: Recently, academic studies suggest that global growth of airway allergic disease has a close association with dietary changes including reduced consumption of fiber. Therefore, appropriate dietary fiber supplementation might be potential to prevent airway allergic disease (AAD). OBJECTIVE: We investigated whether dietary fiber intake suppressed the induction of AAD and tried to elucidate the possible underlying mechanisms. METHODS: The control mice and AAD model mice fed with 4% standard-fiber chow, while low-fiber group of mice fed with a 1.75% low-fiber chow. The two fiber-intervened groups including mice, apart from a standard-fiber diet, were also intragastric (i.g.) administrated daily with poorly fermentable cellulose or readily fermentable pectin (0.4% of daily body weight), respectively. All animals except normal mice were sensitized and challenged with ovalbumin (OVA) to induce airway allergic inflammation. Hallmarks of AAD were examined by histological analysis and ELISA. The variation in intestinal bacterial composition was assessed by qualitative analysis of 16S ribosomal DNA (rDNA) content in fecal samples using real-time PCR. RESULTS: Low-fiber diet aggravated inflammatory response in ovalbumin-induced allergic mice, whereas dietary fiber intake significantly suppressed the allergic responses, attenuated allergic symptoms of nasal rubbing and sneezing, decreased the pathology of eosinophil infiltration and goblet cell metaplasia in the nasal mucosa and lung, inhibited serum OVA-specific IgE levels, and lowered the levels of Th2 cytokines in NALF and BALF, but, increased Th1 (IFN-γ) cytokines. Additionally, dietary fiber intake also increased the proportion of Bacteroidetes and Actinobacteria, and decreased Firmicutes and Proteobacteria. Levels of probiotic bacteria, such as Lactobacillus and Bifidobacterium, were upgraded significantly. CONCLUSION: Long-term deficiency of dietary fiber intake increases the susceptibility to AAD, whereas proper fiber supplementation promotes effectively the balance of Th1/Th2 immunity and then attenuates allergic inflammatory responses significantly, as well as optimizes the structure of intestinal microbiota, which suggests potential for novel preventive and therapeutic intervention.

Is a high-fiber diet able to influence ovalbumin-induced allergic airway inflammation in a mouse model?

BACKGROUND: More recently, a large amount of experimental and clinical discovered that dietary- fiber intake would decrease the susceptibility to allergic airway disease (AAD) and respiratory inflammation. OBJECTIVE: To investigate whether a fiber-intake supplement is able to influence the induction of AAD and to elucidate the interactive relationship. METHODS: AAD model mice and control mice were raised on a fundamental diet with standard 4% fiber content, whereas other mice were fed a 10% fiber-content diet in the high fiber-content group, along with a 25% fiber-content diet instead in very-high fiber-content group. All experimental mice were sensitized and challenged with ovalbumin to induce allergic inflammation in both the upper and lower airways. Hallmarks of AAD were examined in terms of eosinophil infiltration and goblet cell metaplasia in subepithelial mucosa, T-helper type 1 (Th1) to Th2 skewing of the immune response. Furthermore, to elucidate the interrelations, we generated 16S ribosomal DNA from fecal samples and further validated the variation of colony composition in each group. RESULTS: The excessive high-fiber supplement induced a promoting effect rather than a suppressive effect, including a rise in nasal rubbing and sneezing, an increase in eosinophil inflammation and goblet cell metaplasia in subepithelial mucosa, and promoted Th2 skewing of the immune response as well as the production of serum levels of ovalbumin-specific immunoglobulin E. Moreover, overconsumption of dietary fiber greatly altered the construction of bacterial flora in the intestinal tract, including an increased proportion of Firmicutes, Actinobacteria, and Proteobacteria, and a decreased proportion of Bacteroidetes. CONCLUSION: Our work indicated that, instead of a protecting impact, excessive fiber intake preformed a negative influence on the induction of AAD. Therefore, we suspected that an excessive supplement of dietary fiber might not be an advisable method for the prevention and treatment of AADs.