Ligand-engineered bandgap stability in mixed-halide perovskite LEDs.

Lead halide perovskites are promising semiconductors for light-emitting applications because they exhibit bright, bandgap-tunable luminescence with high colour purity1,2. Photoluminescence quantum yields close to unity have been achieved for perovskite nanocrystals across a broad range of emission colours, and light-emitting diodes with external quantum efficiencies exceeding 20 per cent-approaching those of commercial organic light-emitting diodes-have been demonstrated in both the infrared and the green emission channels1,3,4. However, owing to the formation of lower-bandgap iodide-rich domains, efficient and colour-stable red electroluminescence from mixed-halide perovskites has not yet been realized5,6. Here we report the treatment of mixed-halide perovskite nanocrystals with multidentate ligands to suppress halide segregation under electroluminescent operation. We demonstrate colour-stable, red emission centred at 620 nanometres, with an electroluminescence external quantum efficiency of 20.3 per cent. We show that a key function of the ligand treatment is to 'clean' the nanocrystal surface through the removal of lead atoms. Density functional theory calculations reveal that the binding between the ligands and the nanocrystal surface suppresses the formation of iodine Frenkel defects, which in turn inhibits halide segregation. Our work exemplifies how the functionality of metal halide perovskites is extremely sensitive to the nature of the (nano)crystalline surface and presents a route through which to control the formation and migration of surface defects. This is critical to achieve bandgap stability for light emission and could also have a broader impact on other optoelectronic applications-such as photovoltaics-for which bandgap stability is required.

The Wnt Antagonist Dickkopf-1 Promotes Pathological Type 2 Cell-Mediated Inflammation.

Exposure to a plethora of environmental challenges commonly triggers pathological type 2 cell-mediated inflammation. Here we report the pathological role of the Wnt antagonist Dickkopf-1 (Dkk-1) upon allergen challenge or non-healing parasitic infection. The increased circulating amounts of Dkk-1 polarized T cells to T helper 2 (Th2) cells, stimulating a marked simultaneous induction of the transcription factors c-Maf and Gata-3, mediated by the kinases p38 MAPK and SGK-1, resulting in Th2 cell cytokine production. Circulating Dkk-1 was primarily from platelets, and the increase of Dkk-1 resulted in formation of leukocyte-platelet aggregates (LPA) that facilitated leukocyte infiltration to the affected tissue. Functional inhibition of Dkk-1 impaired Th2 cell cytokine production and leukocyte infiltration, protecting mice from house dust mite (HDM)-induced asthma or Leishmania major infection. These results highlight that Dkk-1 from thrombocytes is an important regulator of leukocyte infiltration and polarization of immune responses in pathological type 2 cell-mediated inflammation.

Massilia agrisoli sp. nov., isolated from rhizospheric soil of banana.

A Gram-stain-negative, aerobic, short rod-shaped and motile novel bacterial strain, designated MAHUQ-52T, was isolated from the rhizospheric soil of a banana plant. Colonies grew at 10-35 °C (optimum, 28 °C), pH 6.0-9.5 (optimum, pH 7.0-7.5), and in the presence of 0-1.0 % NaCl (optimum 0 %). The strain was positive for catalase and oxidase tests, as well as hydrolysis of gelatin, casein, starch and Tween 20. Based on the results of phylogenetic analysis using 16S rRNA gene and genome sequences, strain MAHUQ-52T clustered together within the genus Massilia. Strain MAHUQ-52T was closely related to Massilia soli R798T (98.6 %) and Massilia polaris RP-1-19T (98.3 %). The novel strain MAHUQ-52T has a draft genome size of 4 677 454 bp (25 contigs), annotated with 4193 protein-coding genes, 64 tRNA and 19 rRNA genes. The genomic DNA G+C content was 63.0 %. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain MAHUQ-52T and closely related type strains were ≤88.4 and 35.8 %, respectively. The only respiratory quinone was ubiquinone-8. The major fatty acids were identified as C16 : 0 and summed feature 3 (C15 : 0 iso 2-OH and/or C16 : 1 ω7c). Strain MAHUQ-52T contained phosphatidylethanolamine, diphosphatidylglycerol and phosphatidylglycerol as the major polar lipids. On the basis of dDDH and ANI values, as well as genotypic, chemotaxonomic and physiological data, strain MAHUQ-52T represents a novel species within the genus Massilia, for which the name Massilia agrisoli sp. nov. is proposed, with MAHUQ-52T (=KACC 21999T=CGMCC 1.18577T) as the type strain.

Phonozen-mediated photodynamic therapy comparing two wavelengths in a mouse model of peritoneal carcinomatosis.

BACKGROUND: This study assessed the therapeutic efficacy of intraperitoneal photodynamic therapy (PDT) using photosensitizer activation at two different wavelengths, 405 and 664 nm, in a mouse model of peritoneal carcinomatosis. METHODS: The dark and light cytotoxicity of chlorin e6-polyvinylpyrrolidone (Phonozen) were measured in vitro under 402 ± 14 and 670 ± 18 nm LED activation in bioluminescent human gastric cancer cells, MKN45-luc. Cell viability was measured at 6 h after irradiation using the PrestoBlue assay. Corresponding in vivo studies were performed in athymic nude mice by intraperitoneal injection of 1 × 106 MKN45-luc cells. PDT was performed 10 d after tumor induction and comprised intraperitoneal injection of Phonozen followed by light irradiation at 3 h, delivered by a diffusing-tip optical fiber placed in the peritoneal cavity and coupled to a 405 or 664 nm diode laser to deliver a total energy of 50 J (20 mice per cohort). Whole-body bioluminescence imaging was used to track the tumor burden after PDT out to 130 days, and 5 mice in each cohort were sacrificed at 4 h post treatment to measure the acute tumor necrosis. RESULTS: Photosensitizer dose-dependent photocytotoxicity was higher in vitro at 405 than 664 nm. In vivo, PDT reduced the tumor growth rate at both wavelengths, with no statistically significant difference. There was substantial necrosis, and median survival was significantly prolonged at both wavelengths compared with controls (46 and 46 vs. 34 days). CONCLUSIONS: Phonozen-mediated PDT results in significant cytotoxicity in vitro as well as tumor necrosis and prolonged survival in vivo following intraperitoneal light irradiation. Blue light was more photocytotoxic than red in vitro and had marginally higher efficacy in vivo.

Blue Perovskite Nanocrystal Light-Emitting Diodes: Overcoming RuddlesdenPopper Fault-Induced Nonradiative Recombination via Post-Halide Exchange.

Metal halide perovskites (MHPs) have gained traction as emitters owing to their excellent optical properties, such as facile bandgap tuning, defect tolerance, and high color purity. Nevertheless, blue-emitting MHP light-emitting diodes (LEDs) show only marginal progress in device efficiency compared with green and red LEDs. Herein, the origin of the drop in efficiency of blue-emitting perovskite nanocrystals (PNCs) by mixing halides and the genesis of Ruddlesden-Popper faults (RPFs) in CsPbBrX Cl3-X nanocrystals is investigated. Using scanning transmission electron microscopy and density functional theory calculations, the authors have found that RPFs induce possible nonradiative recombination pathways owing to the high chloride vacancy concentration nearby. The authors further confirm that the blue-emitting PNCs do not show RPFs post-halide exchange in the CsPbBr3 nanocrystals. By introducing the post-halide exchange treatment, high-efficiency pure blue-emitting (464 nm) PNC-based LEDs with an external quantum efficiency of 2.1% and excellent spectral stability with a full-width at half-maximum of 14 nm are obtained.

Triphenylamine-Based Conjugated Polyelectrolyte as a Hole Transport Layer for Efficient and Scalable Perovskite Solar Cells.

π-Conjugated polyelectrolytes (CPEs) have been studied as interlayers on top of a separate hole transport layer (HTL) to improve the wetting, interfacial defect passivation, and crystal growth of perovskites. However, very few CPE-based HTLs have been reported without rational molecular design as ideal HTLs for perovskite solar cells (PeSCs). In this study, the authors synthesize a triphenylamine-based anionic CPE (TPAFS-TMA) as an HTL for p-i-n-type PeSCs. TPAFS-TMA has appropriate frontier molecular orbital (FMO) levels similar to those of the commonly used poly(bis(4-phenyl)-2,4,6-trimethylphenylamine) (PTAA) HTL. The ionic and semiconducting TPAFS-TMA shows high compatibility, high transmittance, appropriate FMO energy levels for hole extraction and electron blocking, as well as defect passivating properties, which are confirmed using various optical and electrical analyses. Thus, the PeSC with the TPAFS-TMA HTL exhibits the best power conversion efficiency (PCE) of 20.86%, which is better than that of the PTAA-based device (PCE of 19.97%). In addition, it exhibits negligible device-to-device variations in its photovoltaic performance, contrary to the device with PTAA. Finally, a large-area PeSC (1 cm2 ) and mini-module (3 cm2 ), showing PCEs of 19.46% and 18.41%, respectively, are successfully fabricated. The newly synthesized TPAFS-TMA may suggest its great potential as an HTL for large-area PeSCs.

Pseudomonas oryzagri sp. nov., isolated from a rice field soil.

A Gram-stain-negative, aerobic, rod-shaped and non-motile novel bacterial strain, designated MAHUQ-58T, was isolated from soil sample of a rice field. The colonies were observed to be light pink-coloured, smooth, spherical and 0.6-1.0 mm in diameter when grown on nutrient agar (NA) medium for 2 days. Strain MAHUQ-58T was found to be able to grow at 15-40 °C, at pH 5.5-10.0 and with 0-1.0 % NaCl (w/v). Cell growth occurred on tryptone soya agar, Luria-Bertani agar, NA, MacConkey agar and Reasoner's 2A agar. The strain was found to be positive for both oxidase and catalase tests. The strain was positive for hydrolysis of Tween 20 and l-tyrosine. According to the 16S rRNA gene sequence comparisons, the isolate was identified as a member of the genus Pseudomonas and to be closely related to Pseudomonas oryzae WM-3T (98.9 % similarity), Pseudomonas linyingensis LYBRD3-7T (97.7 %), Pseudomonas sagittaria JCM 18195 T (97.6 %) and Pseudomonas guangdongensis SgZ-6T (97.2 %). The novel strain MAHUQ-58T has a draft genome size of 4 536 129 bp (46 contigs), annotated with 4064 protein-coding genes, 60 tRNA genes and four rRNA genes. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain MAHUQ-58T and four closely related type strains were in the range of 85.5-89.5 % and 29.5-38.0 %, respectively. The genomic DNA G+C content was determined to be 67.0 mol%. The predominant isoprenoid quinone was ubiquinone 9. The major fatty acids were identified as C16:0, summed feature 3 (C16 : 1 ω6c and/or C16 : 1 ω7c) and summed feature 8 (C18 : 1 ω6c and/or C18 : 1 ω7c). On the basis of dDDH and ANI values, genotypic results, and chemotaxonomic and physiological data, strain MAHUQ-58T represents a novel species within the genus Pseudomonas, for which the name Pseudomonas oryzagri sp. nov. is proposed, with MAHUQ-58T (=KACC 22005T=CGMCC 1.18518T) as the type strain.

Implementation and Practice of Deep Learning-Based Instance Segmentation Algorithm for Quantification of Hepatic Fibrosis at Whole Slide Level in Sprague-Dawley Rats.

Exponential development in artificial intelligence or deep learning technology has resulted in more trials to systematically determine the pathological diagnoses using whole slide images (WSIs) in clinical and nonclinical studies. In this study, we applied Mask Regions with Convolution Neural Network (Mask R-CNN), a deep learning model that uses instance segmentation, to detect hepatic fibrosis induced by N-nitrosodimethylamine (NDMA) in Sprague-Dawley rats. From 51 WSIs, we collected 2011 cropped images with hepatic fibrosis annotations. Training and detection of hepatic fibrosis via artificial intelligence methods was performed using Tensorflow 2.1.0, powered by an NVIDIA 2080 Ti GPU. From the test process using tile images, 95% of model accuracy was verified. In addition, we validated the model to determine whether the predictions by the trained model can reflect the scoring system by the pathologists at the WSI level. The validation was conducted by comparing the model predictions in 18 WSIs at 20× and 10× magnifications with ground truth annotations and board-certified pathologists. Predictions at 20× showed a high correlation with ground truth (R2 = 0.9660) and a good correlation with the average fibrosis rank by pathologists (R2 = 0.8887). Therefore, the Mask R-CNN algorithm is a useful tool for detecting and quantifying pathological findings in nonclinical studies.

Lactobacillus acidophilus PIN7 paraprobiotic supplementation ameliorates DSS-induced colitis through anti-inflammatory and immune regulatory effects.

AIMS: This study aimed to evaluate the efficacy of paraprobiotics Lactobacillus acidophilus PIN7 supplementation against dextran sodium sulphate (DSS)-induced colitis in mice and to determine their mechanisms of the action. METHODS AND RESULTS: Ten-week-old female BALB/C mice were randomly divided into five groups. Each group was administered with PBS (control and DSS group), live PIN7 (LIVE group), heat-killed PIN7 (HEAT group) or lysozyme-treated PIN7 (LYSOZYME group) for 10 days followed by 2.5% DSS supply in drinking water for 5 days except for the control group. Colitis-associated DAI scores were significantly (p < 0.05) attenuated in HEAT and LYSOZYME group. The HEAT group exhibited significantly (p < 0.05) lower colonic tissue damage score compared to the DSS group. Furthermore, HEAT and LYSOZYME groups showed significantly (p < 0.05) higher colonic expressions of toll-like receptor (TLR) 6 and intestinal junction protein E-cadherin and occludin compared to the DSS group. LYSOZYME group showed significantly (p < 0.05) lower colonic expressions of Th2 cell-associated pro-inflammatory molecules, namely GATA3 and IL-4, and higher expression of anti-inflammatory NLRP6 and IL-18 compared to the DSS group. Also, HEAT group exhibited significantly (p < 0.05) lower colonic p-IκBα expression compared to the DSS group, while COX-2 expression was significantly (p < 0.05) suppressed by both paraprobiotics supplementation. Paraprobiotics significantly altered the composition of the intestinal microbiota. CONCLUSION: Paraprobiotic L. acidophilus PIN7 ameliorated DSS-induced colitis by regulating immune-modulatory TLR6 signalling and gut microbiota composition. SIGNIFICANCE AND IMPACT OF THE STUDY: This study suggests paraprobiotic L. acidophilus PIN7 are superior candidates to prevent intestinal inflammation associated with dysregulated immune responses.

Positional scanning of natural product hispidol's ring-B: discovery of highly selective human monoamine oxidase-B inhibitor analogues downregulating neuroinflammation for management of neurodegenerative diseases.

Multifunctional molecules might offer better treatment of complex multifactorial neurological diseases. Monoaminergic pathways dysregulation and neuroinflammation are common convergence points in diverse neurodegenerative and neuropsychiatric disorders. Aiming to target these diseases, polypharmacological agents modulating both monoaminergic pathways and neuroinflammatory were addressed. A library of analogues of the natural product hispidol was prepared and evaluated for inhibition of monoamine oxidases (MAOs) isoforms. Several molecules emerged as selective potential MAO B inhibitors. The most promising compounds were further evaluated in vitro for their impact on microglia viability, induced production of proinflammatory mediators and MAO-B inhibition mechanism. Amongst tested compounds, 1p was a safe potent competitive reversible MAO-B inhibitor and inhibitor of microglial production of neuroinflammatory mediators; NO and PGE2. In-silico study provided insights into molecular basis of the observed selective MAO B inhibition. This study presents compound 1p as a promising lead compound for management of neurodegenerative disease.

Distribution and characterization of prophages in Lactobacillus plantarum derived from kimchi.

Prophage distribution and phage characteristics based on the genome of Lactobacillus plantarum derived from kimchi were investigated. Prophage genomes retrieved from a database were analyzed in silico with prophage inducibility. Twenty-one kimchi-derived L. plantarum had at least one intact prophage, including a putative cryptic state on the chromosome. They were all confirmed to belong to the Siphoviridae family. Intact prophages can be classified into three different groups: PM411-like, Sha1-like, and unclassified phage groups. Some prophage regions were encoded with superinfection exclusion proteins and orphan methylases, suggesting that the phages co-evolved with their hosts. Interestingly, prophage inducibility showed that only DNA damage could induce prophages and that pH stresses by organic acids could not. Therefore, the prophage of L. plantarum did not affect the host unless DNA was damaged, and it would hardly affect the viability of the host through phage induction during kimchi fermentation. Our results might provide insights into the distribution and non-inducibility of prophages, existence of phage-immunity genes, and role of plant-derived L. plantarum prophages in host survival during late acidic kimchi fermentation.

Distal femoral phenotypes in Asian varus osteoarthritic knees.

PURPOSE: There has been a general consensus regarding the varus phenotype of the proximal tibia in osteoarthritic patients with varus knee alignment of the whole limb. However, a valgus phenotype of the distal femur may occur in osteoarthritic patients with varus knee alignment. This study evaluated the distal femur phenotype in varus osteoarthritic knees. METHODS: This study included 128 patients who underwent primary total knee arthroplasty (TKA) by computer-assisted navigation for primary medial osteoarthrosis with varus knee alignment. The hip-knee-ankle (HKA) angle, medial proximal tibial angle (MPTA), lateral distal femoral angle (LDFA), and joint line convergence angle (JLCA) were measured on which radiographs preoperatively. The radiographic parameters were compared between groups with HKA angle varus ≥ 10° and < 10°. RESULTS: The MPTA was significantly lower (4°) in the HKA angle varus ≥ 10° group than in the < 10° group (82.13° vs. 86.13° P = 0.001), but the LDFA did not differ significantly between the groups (89.81° vs. 89.19° P = 0.181). Regarding the JLCA, the varus ≥ 10° group showed a 1.3° greater lateral widening than the varus < 10° group (4.87 vs. 3.56, P = 0.002). The MPTA was the only independent predictor of the MA of the lower limb (ß = -  0.353, P < 0.001). CONCLUSION: One-third of varus osteoarthritic knees had a distal femur valgus phenotype. Varus knee alignment was mainly affected by proximal tibia varus rather than by distal femur varus. LEVEL OF EVIDENCE: Level III, consecutive case series.

Synthesis and Evaluation of Serinolamide Derivatives as Sphingosine-1-Phosphate-1 (S1P1) Receptor Agonists.

Sphingosine-1-phosphate-1 (S1P1) receptor agonists are well-known drugs for treating multiple sclerosis (MS) caused by autoreactive lymphocytes that attack the myelin sheath. Therefore, an effective therapeutic strategy is to reduce the lymphocytes in the blood by inducing S1P1 receptor internalization. We synthesized serinolamide A, a natural product of the sea, and performed S1P1 receptor internalization assay to evaluate functionally antagonistic S1P1 receptor agonist activity. In order to synthesize derivatives with better efficacy than serinolamide A and B, new derivatives were synthesized by introducing the phenyl ring moiety of fingolimod. Among them, compounds 19 and 21 had superior S1P1 agonistic effects to serinolamide. We also confirmed that compound 19 effectively inhibited lymphocyte outflow in peripheral lymphocyte count (PLC) assay.

Arctigenin induces caspase-dependent apoptosis in FaDu human pharyngeal carcinoma cells.

The present study was carried out to investigate the effect of Arctigenin on cell growth and the mechanism of cell death elicited by Arctigenin were examined in FaDu human pharyngeal carcinoma cells. To determine the apoptotic activity of Arctigenin in FaDu human pharyngeal carcinoma cells, cell viability assay, DAPI staining, caspase activation analysis, and immunoblotting were performed. Arctigenin inhibited the growth of cells in a dose-dependent manner and induced nuclear condensation and fragmentation. Arctigenin-treated cells showed caspase-3/7 activation and increased apoptosis versus control cells. FasL, a death ligand associated with extrinsic apoptotic signaling pathways, was up-regulated by Arctigenin treatment. Moreover, caspase-8, a part of the extrinsic apoptotic pathway, was activated by Arctigenin treatments. Expressions of anti-apoptotic factors such as Bcl-2 and Bcl-xL, components of the mitochondria-dependent intrinsic apoptosis pathway, significantly decreased following Arctigenin treatment. The expressions of pro-apoptotic factors such as BAX, BAD and caspase-9, and tumor suppressor -53 increased by Arctigenin treatments. In addition, Arctigenin activated caspase-3 and poly (ADP-ribose) polymerase (PARP) induced cell death. Arctigenin also inhibited the proliferation of FaDu cells by the suppression of p38, NF-κB, and Akt signaling pathways. These results suggest that Arctigenin may inhibit cell proliferation and induce apoptotic cell death in FaDu human pharyngeal carcinoma cells through both the mitochondria-mediated intrinsic pathway and the death receptor-mediated extrinsic pathway.

Paenibacillus roseus sp. nov., a ginsenoside-transforming bacterium isolated from forest soil.

A novel, pink-pigmented, Gram-stain-positive, aerobic, motile, rod-shaped and ginsenoside-converting bacterium, designated strain MAHUQ-46T, was isolated from soil of a forest. Strain MAHUQ-46T grew in the pH range 6.0-9.0 (optimum, 7.5), at temperatures between 10 and 37 °C (optimum, 30 °C) and at 0-3% (w/v) NaCl (optimum, 0.5%). 16S rRNA gene sequence analysis showed that strain MAHUQ-46T was closely related to Paenibacillus pinihumi S23T (97.3% similarity), followed by Paenibacillus elymi KUDC6143T (96.7%). The draft genome of strain MAHUQ-46T had a total length of 5,367,904 base pairs. A total of 4,857 genes were identified, in which 4,629 were protein-coding genes and 137 were RNA genes. The genome annotation of MAHUQ-46T showed 172 carbohydrate genes, some of them may be responsible for the biosynthesis of ginsenoside Rd from major ginsenoside Rb1. The DNA G + C content was 48.4 mol% and the major quinone was MK-7. Main fatty acids of strain MAHUQ-46T were C15: 0 anteiso, C16: 0 and C17: 0 anteiso. The polar lipids comprised phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidyl-N-methylethanolamine, two unidentified aminophospholipids and five unidentified phospholipids. Diagnostic diamino acid of peptidoglycan was meso-diaminopimelic acid. The novel strain MAHUQ-46T was able to rapidly synthesize ginsenoside Rd from major ginsenoside Rb1. The synthesized ginsenoside was confirmed by TLC and HPLC analysis. According to the phenotypic, genetic and chemotaxonomic evidence, strain MAHUQ-46T was clearly distinguishable from validly published species of genus Paenibacillus and should, therefore, be categorized as a novel species for which the name Paenibacillus roseus sp. nov. is proposed. The type strain is MAHUQ-46T (= KACC 21242T = CGMCC 1.17353T).

Niastella soli sp. nov., isolated from rhizospheric soil of a persimmon tree.

A Gram-stain-negative, aerobic, motile and rod-shaped novel bacterial strain, designated MAH-29T, was isolated from rhizospheric soil of a persimmon tree. The colonies were light pink coloured, smooth, spherical and 0.1-0.8 mm in diameter when grown on Reasoner's 2A (R2A) agar for 2 days. Strain MAH-29T was able to grow at 20-37 °C, at pH 5.0-8.5 and at 0-2.0 % NaCl. Cell growth occurred on nutrient agar and R2A agar. The strain was positive in both oxidase and catalase tests. According to the 16S rRNA gene sequence comparisons, the isolate was identified as a member of the genus Niastella and was closely related to Niastella vici DJ57T (97.7 % similarity), Niastella koreensis GR20-10T (97.1 %) and Niastella yeongjuensis GR20-13T (97.0 %). Strain MAH-29T has a draft genome size of 8 876 333 bp (31 contigs), annotated with 6920 protein-coding genes, 61 tRNA and four rRNA genes. The average nucleotide identity and digital DNA-DNA hybridization values between strain MAH-29T and three closely related type strains were in the range of 78.2-83.2 % and 22.1-27.0 %, respectively. The genomic DNA G+C content was 43.8 mol%. The predominant isoprenoid quinone was menaquinone 7. The major fatty acids were identified as iso-C15:0, iso-C15:1 G and iso-C17:0 3OH. On the basis of DNA-DNA hybridization results, genotypic analysis and chemotaxonomic and physiological data, strain MAH-29T represents a novel species within the genus Niastella, for which the name Niastella soli sp. nov. is proposed, with MAH-29T (=KACC 19969T=CGMCC 1.16606T) as the type strain.

Pinibacter aurantiacus gen. nov., sp. nov., isolated from rhizospheric soil of a pine tree.

A Gram-stain-negative, aerobic and rod-shaped novel bacterial strain, designated MAH-26T, was isolated from rhizospheric soil of a pine tree. The colonies were orange coloured, smooth, spherical and 0.7-1.8 mm in diameter when grown on Reasoner's 2A (R2A) agar for 2 days. Strain MAH-26T was able to grow at 10-40 °C, at pH 6.0-9.0 and with 0-1.0 % NaCl. Cell growth occurred on nutrient agar, R2A agar, tryptone soya agar and Luria-Bertani agar. The strain gave positive results in oxidase and catalase tests. Strain MAH-26T was closely related to Flavihumibacter sediminis CJ663T and Parasegetibacter terrae SGM2-10T with a low 16S rRNA gene sequence similarity (92.8 and 92.9 %, respectively) and phylogenetic analysis indicated that the strain formed a distinct phylogenetic lineage from the members of the closely related genera of the family Chitinophagaceae. Strain MAH-26T has a draft genome size of 6 857 405 bp, annotated with 5173 protein-coding genes, 50 tRNA and two rRNA genes. The genomic DNA G+C content was 41.5 mol%. The predominant isoprenoid quinone was menaquinone 7. The major fatty acids were identified as iso-C15:0, iso-C15:1 G and iso-C17:0 3OH. On the basis of phylogenetic inference and phenotypic, chemotaxonomic and molecular properties, strain MAH-26T represents a novel species of a novel genus of the family Chitinophagaceae, for which the name Pinibacter aurantiacus gen. nov., sp. nov. is proposed. The type strain of Pinibacter aurantiacus is MAH-26T (=KACC 19749T=CGMCC 1.13701T).

Discovery of novel and potent safinamide-based derivatives as highly selective hMAO-B inhibitors for treatment of Parkinson's disease (PD): Design, synthesis, in vitro, in vivo and in silico biological studies.

Up to date, the current clinical practice employs only symptomatic treatments for management of Parkinson's disease (PD) but unable to stop disease progression. The discovery of new chemical entities endowed with potent and selective human monoamine oxidase B (hMAO-B) inhibitory activity is a clinically relevant subject. Herein, a structural optimization strategy for safinamide (a well-known second generation hMAO-B inhibitor) afforded a series of thirty-six safinamide-derived new analogs (4aa-bj). Most compounds showed promising inhibitory activities against hMAO-B (>70% inhibition at a single dose concentration of 10 µM), with no apparent effect on hMAO-A at 100 µM. Moreover, while six compounds (4ak, 4as, 4az, 4be, 4bg, and 4bi) exhibited potent double-digit nanomolar activities over hMAO-B with IC50 values of 29.5, 42.2, 22.3, 18.8, 42.2, and 33.9 nM, respectively, three derivatives (4aq, 4at, and 4bf), possessing the same carboxamide moiety (2-pyrazinyl), showed the most potent single-digit nanomolar activities (IC50 = 9.7, 5.1, and 3.9 nM, respectively). Compound 4bf revealed an excellent selectivity index (SI > 25641) with a 29-fold increase compared to safinamide (SI > 892). A structure activity relationship along with molecular docking simulations provided insights into enzyme - inhibitor interactions and a rational for the observed activity. In an in vivo MPTP-induced mouse model of PD, oral administration of compound 4bf significantly protected nigrostriatal dopaminergic neurons as revealed by tyrosine hydroxylase staining and prevented MPTP-induced Parkinsonism as revealed by motor behavioral assays. Accordingly, we present compound 4bf as a novel, highly potent, and selective hMAO-B inhibitor with an effective therapeutic profile for relieving PD.

Discovery of 3,4-dichloro-N-(1H-indol-5-yl)benzamide: A highly potent, selective, and competitive hMAO-B inhibitor with high BBB permeability profile and neuroprotective action.

Since there is no disease-modifying treatment discovered yet for Parkinson's disease (PD), there is still a vital need to develop novel selective monoamine oxidase B (MAO-B) inhibitors as promising therapeutically active candidates for PD patients. Herein, we report the design, synthesis, and full characterization of new twenty-six indole derivatives as potential human MAO-B (hMAO-B) selective inhibitors. Six compounds (2i, 3b-e, and 5) exhibited low micromolar to nanomolar inhibitory activities over hMAO-B; compared to our recently reported N-substituted indole-based lead compound VIII (hMAO-B IC50 = 777 nM), compound 5 (3,4-dichloro-N-(1H-indol-5-yl)benzamide) exhibited 18-fold increase in potency (IC50 = 42 nM). A selectivity study over hMAO-A revealed an excellent selectivity index of compound 5 (SI > 2375) with a 47-fold increase compared to rasagiline (II, a well-known MAO-B inhibitor, SI > 50). A further kinetic evaluation of compound 5 over hMAO-B showed a reversible and competitive mode of inhibition with Ki value of 7 nM. Highly effective permeability and high CNS bioavailability of compound 5 with Pe = 54.49 × 10-6 cm/s were demonstrated. Compound 5 also exhibited a low cytotoxicity profile and a promising neuroprotective effect against the 6-hydroxydopamine-induced neuronal cell damage in PC12 cells, which was more effective than that of rasagiline. Docking simulations on both hMAO-B and hMAO-A supported the in vitro data and served as further molecular evidence. Accordingly, we report the discovery of compound 5 as one of the most potent indole-based MAO-B inhibitors to date which is noteworthy to be further evaluated as a promising agent for PD treatment.

Identification and evaluation of a napyradiomycin as a potent Nrf2 activator: Anti-oxidative and anti-inflammatory activities.

Natural products with antioxidant and anti-inflammatory properties are important sources of therapeutic agents. The nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is a well-known defense system against oxidative stress. In this study, a panel of extracts of plants, fungi, and bacteria were screened for Nrf2 activation in a cell-based assay and a crude extract of cultured marine Streptomyces sp. YP127 was found to activate Nrf2. Chemical investigation of the extracts led to isolation of a series of napyradiomycins that activate Nrf2. Among them, napyradiomycin, 16Z-19-hydroxynapyradiomycin A1 (1) exhibited the highest Nrf2-activating efficacy. Compound 1 was further confirmed to induce both mRNA and protein levels of Nrf2-dependent antioxidant enzyme genes in BV-2 microglial cells and suppress inflammatory mediators and intracellular reactive oxygen species. Our findings confirm the antioxidant and anti-inflammatory properties of compound 1, making it a promising therapeutic natural compound for various diseases associated with oxidative stress and inflammation.