Neuroprotective Effects of AER-271 in a tMCAO Mouse Model: Modulation of Autophagy, Apoptosis, and Inflammation.

Following ischemic stroke, aquaporin 4 (AQP4) expression modifications have been associated with increased inflammation. However, the underlying mechanisms are not fully understood. This study aims to elucidate the mechanistic basis of post-cerebral ischemia-reperfusion (I/R) inflammation by employing the AQP4-specific inhibitor, AER-271. The middle cerebral artery occlusion (MCAO) model was used to induce ischemic stroke in mice. C57BL/6 mice were randomly allocated into four groups: sham operation, I/R, AER-271, and 2-(nicotinamide)-1,3,4-thiadiazole (TGN-020) treatment, with observations recorded at 1 day, 3 days, and 7 days post-tMCAO. Each group consisted of 15 mice. Procedures included histological examination through HE staining, neurological scoring, Western blot analysis, and immunofluorescence staining. AER-271 treatment yielded significant improvements in post-stroke weight recovery and neurological scores, accompanied by a reduction in cerebral infarction volume. Moreover, AER-271 exhibited a noticeable influence on autophagic and apoptotic pathways, affecting the activation of both pro-inflammatory and anti-inflammatory cytokines. Alterations in the levels of inflammatory biomarkers MCP-1, NLRP3, and caspase 1 were also detected. Finally, a comparative assessment of the effects of AER-271 and TGN-020 in mitigating apoptosis and microglial polarization in ischemic mice revealed neuroprotective effects with no significant difference in efficacy. This study provides essential insights into the neuroprotective mechanisms of AER-271 in cerebral ischemia-reperfusion injury, offering potential clinical applications in the treatment of ischemic cerebrovascular disorders.

Clinical Immunological Characteristics of Anti-Interferon-γ Autoantibodies Syndrome: A 3 Year Prospective Cohort Study.

BACKGROUND: Anti-interferon-γ autoantibodies (AIGAs) syndrome is susceptible to disseminated opportunistic infections due to increased AIGAs, but its clinical immunological characteristics remain unrecognized. METHODS: We conducted a prospective cohort study between January 2021 and December 2023, recruiting patients with opportunistic infections who were categorized into AIGAs-positive and AIGAs-negative groups. Clinical immunological data and outcomes were documented. A subset of AIGAs-positive patients received glucocorticoid treatment, and its effectiveness was evaluated. RESULTS: A total of 238 patients were enrolled, with 135 AIGAs-positive and 103 AIGAs-negative patients. AIGAs-positive patients showed higher rates of multiple pathogen dissemination, shorter progression-free survival (PFS), and increased exacerbation frequency. They also showed elevated erythrocyte sedimentation rate (ESR), globulin (GLB), immunoglobulin (Ig)G, IgE, and IgG4 levels. Among the 70 AIGAs-positive patients monitored for at least six months, three subtypes were identified: high AIGAs titer with immune damage, high AIGAs titer without immune damage, and low AIGAs titer without immune damage. Of the 55 patients followed for 1 year, decreasing AIGAs titer and immune indices (GLB, IgG, IgE, IgG4) were observed. Among the 31 patients with high AIGAs titer and immune damage treated with low-dose glucocorticoids at the stable phase, reductions were observed in immune indices and AIGAs titer in 67.74% of cases. CONCLUSIONS: AIGAs-positive patients exhibit infectious and immunological characteristics. Elevated AIGAs, IgG, IgG4, and IgE indicate abnormal immune damages. AIGAs titer generally decrease over time. Stable-phase AIGAs-positive patients can be categorized into three subtypes, with those having high AIGAs titer and increased immune indices potentially benefitting from glucocorticoid treatment.

EDA Complex-Enabled Annulation to Access CF2-Containing Tetralones and Quinazolinones Using Persulfates as Electron Donors.

A photocatalyst-free and EDA complex-enabled radical cascade cyclization reaction of inactive alkenes with bromodifluoroacetamides was reported for the divergent synthesis of fluorine-containing tetralones and quinazolinones. In this transformation, persulfates as electron donors and difluoro bromamide as electron acceptors generate the EDA complex. This is a promising photochemical method with advantages such as mild reaction conditions, simple operation, being metal-free, and excellent functional group tolerance.

Autophagy Regulation Attenuates Neuroinflammation and Cognitive Decline in an Alzheimer's Disease Mouse Model with Chronic Cerebral Hypoperfusion.

This study investigates the role of autophagy regulation in modulating neuroinflammation and cognitive function in an Alzheimer's disease (AD) mouse model with chronic cerebral hypoperfusion (CCH). Using the APP23/PS1 mice plus CCH model, we examined the impact of autophagy regulation on cognitive function, neuroinflammation, and autophagic activity. Our results demonstrate significant cognitive impairments in AD mice, exacerbated by CCH, but mitigated by treatment with the autophagy inhibitor 3-methyladenine (3-MA). Dysregulation of autophagy-related proteins, accentuated by CCH, underscores the intricate relationship between cerebral blood flow and autophagy dysfunction in AD pathology. While 3-MA restored autophagic balance, rapamycin (RAPA) treatment did not induce significant changes, suggesting alternative therapeutic approaches are necessary. Dysregulated microglial polarization and neuroinflammation in AD+CCH were linked to cognitive decline, with 3-MA attenuating neuroinflammation. Furthermore, alterations in M2 microglial polarization and the levels of inflammatory markers NLRP3 and MCP1 were observed, with 3-MA treatment exhibiting potential anti-inflammatory effects. Our findings shed light on the crosstalk between autophagy and neuroinflammation in AD+CCH and suggest targeting autophagy as a promising strategy for mitigating neuroinflammation and cognitive decline in AD+CCH.

Flavonoids intake and weight-adjusted waist index: insights from a cross-sectional study of NHANES.

This study conducted data on 15,446 adults to explore the impact of flavonoids on weight-adjusted waist index (WWI). This was a nationwide cross-sectional study among US adults aged 20 years or older. Dietary intake of flavonoids was assessed through 24-h recall questionnaire. WWI was calculated by dividing waist circumference (WC) by the square root of weight. We utilized weighted generalized linear regression to evaluate the association between flavonoids intake and WWI, and restricted cubic splines (RCS) to explore potential non-linear relationships. Our findings indicated that individuals with lower WWI experienced a notable increase in their consumption of total flavonoids, flavanones, flavones, flavan-3-ols, and anthocyanidins intake (ß (95% CI); -0.05(-0.09, -0.01); -0.07(-0.13, 0.00); -0.07(-0.11, -0.02); -0.06(-0.11, 0.00); -0.13(-0.18, -0.08), respectively), with the exception of flavonols and isoflavones. Additionally, consumption of total flavonoids, flavonols, flavanones, isoflavones, and flavan-3-ols had a non-linear relationship with WWI (all P for non-linearity < 0.05). Furthermore, the effect of total flavonoids on WWI varied in race (P for interaction = 0.011), gender (P for interaction = 0.038), and poverty status (P for interaction = 0.002). These findings suggested that increase the intake of flavonoids might prevent abdominal obesity, but further prospective studies are requested before dietary recommendation.

Microbial regulation on refractory dissolved organic matter in inland waters.

The production of refractory dissolved organic matter (RDOM) is complex and closely related to microbial consortia in aquatic ecosystems; however, it is still unclear how microorganisms regulate the production of RDOM and its molecular composition in inland waters. Therefore, we conducted a large-scale survey of inland waters and analyzed the optical and mass spectrometric characteristics of DOM, the microbial community and functional genes, as well as related environmental parameters, to understand the abovementioned issues. Here, the RDOM production was found mainly regulated by microbial (e.g., phylogeny and community assembly) rather than other environmental factors in inland waters. Biostatistical analyses and carbon isotopic evidence indicated that the successive microbial processing from labile DOM to RDOM (i.e., carboxyl-rich alicyclic molecules, CRAMs) was widely present in inland waters, involving the microbially mediated carbon skeleton turnover and heteroatom conversion. There was a significant empirical relationship between CRAMs and the ratio of Proteobacteria to Actinobacteria, highlighting the intraspecific interaction of bacteria more important than other microbial groups (i.e., archaea, eukaryotes, and fungi) for the RDOM production. This study demonstrated a fundamental role of microbial regulation in RDOM production within the inland waters, thereby facilitating future estimation of carbon sequestration potential in inland aquatic ecosystems.

Unraveling the metastatic niche in breast cancer bone metastasis through single-cell RNA sequencing.

PURPOSE: Breast cancer (BRCA) is characterized by a unique metastatic pattern, often presenting with bone metastasis (BoM), posing significant clinical challenges. Through the study of the immune microenvironment in BRCA BoM offer perspectives for therapeutic interventions targeting this specific metastatic manifestation of BRCA. METHODS: This study employs single-cell RNA sequencing and TCGA data analysis to comprehensively compare primary tumors (PT), lymph node metastasis (LN), and BoM. RESULTS AND CONCLUSIONS: Our investigation identifies a metastatic niche in BoM marked by an increased abundance of cancer-associated fibroblasts (CAFs) and reduced immune cell presence. A distinct subtype (State 1) of BRCA BoM cells associated with adverse prognosis is identified. State 1, displaying heightened stemness traits, may represent an initiation phase for BoM in BRCA. Complex cell communications involving tumor, stromal, and immune cells are revealed. Interactions of FN1, SPP1, and MDK correlate with elevated immune cells in BoM. CD46, MDK, and PTN interactions drive myofibroblast activation and proliferation, contributing to tissue remodeling. Additionally, MDK, PTN, and FN1 interactions influence FAP+ CAF activation, impacting cell adhesion and migration in BoM. These insights deepen our understanding of the metastatic niche in breast cancer BoM.

Causal association between type 2 diabetes mellitus and acute suppurative otitis media: insights from a univariate and multivariate Mendelian randomization study.

Background: Type 2 diabetes mellitus (T2DM) and hearing loss (HL) constitute significant public health challenges worldwide. Recently, the association between T2DM and HL has aroused attention. However, possible residual confounding factors and other biases inherent to observational study designs make this association undetermined. In this study, we performed univariate and multivariable Mendelian Randomization (MR) analysis to elucidate the causal association between T2DM and common hearing disorders that lead to HL. Methods: Our study employed univariate and multivariable MR analyses, with the Inverse Variance Weighted method as the primary approach to assessing the potential causal association between T2DM and hearing disorders. We selected 164 and 9 genetic variants representing T2DM from the NHGRI-EBI and DIAGRAM consortium, respectively. Summary-level data for 10 hearing disorders were obtained from over 500,000 participants in the FinnGen consortium and MRC-IEU. Sensitivity analysis revealed no significant heterogeneity of instrumental variables or pleiotropy was detected. Results: In univariate MR analysis, genetically predicted T2DM from both sources was associated with an increased risk of acute suppurative otitis media (ASOM) (In NHGRI-EBI: OR = 1.07, 95% CI: 1.02-1.13, P = 0.012; In DIAGRAM: OR = 1.14, 95% CI: 1.02-1.26, P = 0.016). Multivariable MR analysis, adjusting for genetically predicted sleep duration, alcohol consumption, body mass index, and smoking, either individually or collectively, maintained these associations. Sensitivity analyses confirmed the robustness of the results. Conclusion: T2DM was associated with an increased risk of ASOM. Strict glycemic control is essential for the minimization of the effects of T2DM on ASOM.

Temporal heterogeneity of the root microbiome in Panax ginseng soils across ecological compartments under mild soil disturbance.

Introduction: Knowledge on spatiotemporal heterogeneity of plant root microbiomes is lacking. The diversity of the root microbiome must be revealed for understanding plant-microbe interactions and the regulation of functionally crucial microbial taxa. Methods: We here investigated the dynamics of microbial group characteristics within each soil ecological compartment [rhizoplane (B), rhizosphere (J), and bulk soil (T)] across different cultivation years (year 4: F4 and year 5: F5) by using high-throughput sequencing (16S and ITS). Results: According to the species diversity, microbiome diversity and the ASV (amplified sequence variant) number in the rhizoplane ecotone increased significantly with an increase in the planting years. By contrast, the microbiome diversity of the rhizosphere soil remained relatively stable. PCoA and PERMANOVA analyses revealed that microbial taxa among different planting years and ecological compartments varied significantly. Planting years exerted the least effect on the rhizosphere microbiome, but their impact on fungi in the rhizoplane and bacteria in the bulk soil was the most significant. Discussion: Planting years influenced the microbial community composition in various ecological compartments of ginseng root soil. Potentially harmful fungi such as Cryptococcus (2.83%), Neonectria (0.89%), llyonectria (0.56%), Gibberella (0.41%), Piloderma (4.44%), and Plectosphaerella (3.88%) were enriched in F5B with an increase in planting years, whereas the abundance of potentially beneficial Mortierella increased. Correlation analysis indicated associations between bacterial taxa and soil pH/S-CAT, and between fungal taxa and soil moisture content/total potassium. Our study highlights the significance of changes in rhizoplane fungi and the stability of the rhizosphere microbial community in comprehending plant ecological sustainability.

Temporal patterns of endophytic microbial heterogeneity across distinct ecological compartments within the Panax ginseng root system following deforestation for cultivation.

Alterations in the microbial community significantly impact the yield and quality of ginseng. Yet, the dynamics of microbial community shifts within the root endophytes of ginseng across varying cultivation periods remain inadequately understood. This study zeroes in on the microbial community variations within the xylem (M), phloem (R), and fibrous roots (X) of ginseng during the fourth (F4) and fifth (F5) years of cultivation, aiming to bridge this research gap. We assessed soil physicochemical properties, enzyme activities, and nine individual saponins, complemented by high-throughput sequencing techniques (16S rDNA and ITS) to determine their profiles. The results showed that cultivation years mainly affected the microbial diversity of endophytic bacteria in ginseng fibrous roots compartment: the ASVs number and α-diversity Chao1 index of bacteria and fungi in F5X compartment with higher cultivation years were significantly higher than those in F4X compartment with lower cultivation years. It is speculated that the changes of fibrous roots bacterial groups may be related to the regulation of amino acid metabolic pathway. Such as D-glutamine and D-glutamate metabolism D-glutamine, cysteine and methionine metabolism regulation. The dominant bacteria in ginseng root are Proteobacteria (relative abundance 52.07-80.35%), Cyanobacteria (1.97-42.52%) and Bacteroidota (1.11-5.08%). Firmicutes (1.28-3.76%). There were two dominant phyla: Ascomycota (60.10-93.71%) and Basidiomycota (2.25-30.57%). Endophytic fungi were more closely related to soil physicochemical properties and enzyme activities. AN, TK, OP, SWC and EC were the main driving factors of endophytic flora of ginseng root. Tetracladium decreased with the increase of cultivation years, and the decrease was more significant in phloem (F4R: 33.36%, F5R: 16.48%). The relative abundance of Bradyrhizobium, Agrobacterium and Bacillus in each ecological niche increased with the increase of cultivation years. The relative abundance of Bradyrhizobium and Agrobacterium in F5X increased by 8.35 and 9.29 times, respectively, and Bacillus in F5M increased by 5.57 times. We found a variety of potential beneficial bacteria and pathogen antagonists related to ginseng biomass and saponins, such as Bradyrhizobium, Agrobacterium, Bacillus and Exophiala, which have good potential for practical application and development.

Eosinophil peroxidase promotes bronchial epithelial cells to secrete asthma-related factors and induces the early stage of airway remodeling.

Asthma is a heterogeneous disease characterized by chronic airway inflammation, reversible airflow limitation, and airway remodeling. Eosinophil peroxidase (EPX) is the most abundant secondary granule protein unique to activated eosinophils. In this study, we aimed to illustrate the effect of EPX on the epithelial-mesenchymal transition (EMT) in BEAS-2B cells. Our research found that both EPX and ADAM33 were negatively correlated with FEV1/FVC and FEV1%pred, and positively correlated with IL-5 levels. Asthma patients had relatively higher levels of ADAM33 and EPX compared to the healthy control group. The expression of TSLP, TGF-ß1 and ADAM33 in the EPX intervention group was significantly higher. Moreover, EPX could promote the proliferation, migration and EMT of BEAS-2B cells, and the effect of EPX on various factors was significantly improved by the PI3K inhibitor LY294002. The findings from this study could potentially offer a novel therapeutic target for addressing airway remodeling in bronchial asthma, particularly focusing on EMT.

The pyrexia channel remodels egg-laying of Liriomyza huidobrensis in response to temperature change.

BACKGROUND: The pea leafminer, Liriomyza huidobrensis, is one of the most important insect pests on vegetables and ornamentals. The survival and egg-laying behavior of leafminers are markedly affected by the environment temperature. However, the mechanisms underlying the relationship between egg-laying and temperature are still largely unknown. RESULTS: Here, we find that leafminers have evolved an adaptive strategy to overcome the stress from high or low temperature by regulating oviposition-punching plasticity. We further show that this oviposition-punching plasticity is mediated by the expression of pyx in the ovipositor when subjected to disadvantageous temperature. Specifically, down-regulation of pyx expression in leafminers under low temperature stress led to a significant decrease in the swing numbers of ovipositor and puncture area of the egg spot, and consequently the lower amount of egg-laying compared to leafminers at ambient temperature. Conversely, activation of pyx expression under high temperature stress increased the swing numbers and puncture area, still resulting in a reduction of egg-laying amount. CONCLUSION: Thereby, leafminers are able to coordinate pyx channel expression level and accordingly depress the oviposition. Our study uncovers a molecular mechanism underlying the adaptive strategy in insects that can avoid disadvantageous temperature for reproducing offspring. © 2024 Society of Chemical Industry.

Paraflavitalea pollutisoli sp. nov., Pollutibacter soli gen. nov. sp. nov., Polluticoccus soli gen. nov. sp. nov., and Terrimonas pollutisoli sp. nov., four new members of the family Chitinophagaceae from polluted soil.

A taxonomic investigation was conducted on four bacterial strains isolated from soil contaminated with polycyclic aromatic hydrocarbons and heavy metals. Phylogenetic analysis revealed that these strains belonged to the family Chitinophagaceae. Examination of the 16S rRNA genes indicated that their sequence identities were below 97.6 % compared to any known and validly nominated bacterial species. The genomes of the four strains ranged from 4.12 to 8.76 Mb, with overall G + C molar contents varying from 41.28 % to 50.39 %. Predominant cellular fatty acids included iso-C15:0, iso-C15:1 G, and iso-C17:0 3-OH. The average nucleotide identity ranged from 66.90 % to 74.63 %, and digital DNA-DNA hybridization was 12.5-12.8 %. Based on the genomic and phenotypic features of the new strains, four novel species and two new genera were proposed within the family Chitinophagaceae. The ecological distributions were investigated by data-mining of NCBI databases, and results showed that additional strains or species of the newly proposed taxa were widely distributed in various environments, including polluted soil and waters. Functional analysis demonstrated that strains H1-2-19XT, JS81T, and JY13-12T exhibited resistance to arsenite (III) and chromate (VI). The proposed names for the four novel species are Paraflavitalea pollutisoli (type strain H1-2-19XT = JCM 36460T = CGMCC 1.61321T), Terrimonas pollutisoli (type strain H1YJ31T = JCM 36215T = CGMCC 1.61343T), Pollutibacter soli (type strain JS81T = JCM 36462T = CGMCC 1.61338T), and Polluticoccus soli (type strain JY13-12T = JCM 36463T = CGMCC 1.61341T).

IL-6-Driven Autocrine Lactate Promotes Immune Escape of Uveal Melanoma.

Purpose: Early metastasis, in which immune escape plays a crucial role, is the leading cause of death in patients with uveal melanoma (UM); however, the molecular mechanism underlying UM immune escape remains unclear, which greatly limits the clinical application of immunotherapy for metastatic UM. Methods: Transcriptome profiles were revealed by RNA-seq analysis. TALL-104 and NK-92MI-mediated cell killing assays were used to examine the immune resistance of UM cells. The glycolysis rate was measured by extracellular acidification analysis. Protein stability was evaluated by CHX-chase assay. Immunofluorescence histochemistry was performed to detect protein levels in clinical UM specimens. Results: Continuous exposure to IL-6 induced the expression of both PD-L1 and HLA-E in UM cells, which promoted UM immune escape. Transcriptome analysis revealed that the expression of most metabolic enzymes in the glycolysis pathway, especially the rate-limiting enzymes, PFKP and PKM, was upregulated, whereas enzymes involved in the acetyl-CoA synthesis pathway were downregulated after exposure to IL-6. Blocking the glycolytic pathway and lactate production by knocking down PKM and LDHA decreased PD-L1 and HLA-E protein, but not mRNA, levels in UM cells treated with IL-6. Notably, lactate secreted by IL-6-treated UM cells was crucial in influencing PD-L1 and HLA-E stability via the GPR81-cAMP-PKA signaling pathway. Conclusions: Our data reveal a novel mechanism by which UM cells acquire an immune-escape phenotype by metabolic reprogramming and reinforce the importance of the link between inflammation and immune escape.

In situ hydrodeoxygenation of heavy bio-oil using a Ce/Fe-based oxygen carrier in methanol-zero valent aluminum media.

Resource recovery from solid organic wastes, such as degradable plastics, and upgrading raw bio-oil are important ways for reducing carbon and pollution emissions. Hydrodeoxygenation (HDO) is a common thermochemical treatment to upgrade crude bio-oil. In this study, in order to realize in situ HDO during the hydropyrolysis of heavy bio-oil and degradable plastics, a reduced Fe/Ce oxygen carrier (OC) was used to catalytically remove oxygen from organics under the methanol-zero valent aluminum (ZV Al) media, where the hydrogen was produced during pyrolysis instead of a direct hydrogen supply. The results showed that the reduced OC captured the oxygen from the pyrolysis products of heavy bio-oil and degradable plastic, representing the multi-selectivity of reduced OC to phenols, ketones, etc. The ZV Al system promoted the production and utilization of hydrogen, as evidenced by the increased hydrogen content in gas phase and hydrocarbon content in liquid phase. The hydrocarbon component distribution in the liquid phase increased clearly when hydropyrolysis with degradable plastics addtion, but the excess degradable plastics addition caused increasing of the liquid product viscosity, and decreasing of the liquid products yield for the higher ash content in degradable plastic, and a higher ZV Al amount was required to maintain the hydropyrolysis. Molecular dynamics simulations verified the synergistic effect of degradable plastics and bio-oil by the pyrolysis behavior in different systems and temperatures, and the pyrolysis pathways were proposed. This non-autocatalytic system realized the resource recovery and heavy bio-oil upgrading using an Fe/Ce OC.

Stepwise degradation of organic matters driven by microbial interactions in China΄s coastal wetlands: Evidence from carbon isotope analysis.

The microbial "unseen majority" as drivers of carbon cycle represent a significant source of uncertain climate change. To comprehend the resilience of life forms on Earth to climate change, it is crucial to incorporate knowledge of intricate microbial interactions and their impact to carbon transformation. Combined with carbon stable isotope analysis and high-throughput sequencing technology, the underlying mechanism of microbial interactions for organic carbon degradation has been elucidated. Niche differentiation enabled archaea to coexist with bacteria mainly in a cooperative manner. Bacteria composed of specialists preferred to degrade lighter carbon, while archaea were capable of utilizing heavier carbon. Microbial resource-dependent interactions drove stepwise degradation of organic matter. Bacterial cooperation directly facilitated the degradation of algae-dominated particulate organic carbon, while competitive feeding of archaea caused by resource scarcity significantly promoted the mineralization of heavier particulate organic carbon and then the release of dissolved inorganic carbon. Meanwhile, archaea functioned as a primary decomposer and collaborated with bacteria in the gradual degradation of dissolved organic carbon. This study emphasized microbial interactions driving carbon cycle and provided new perspectives for incorporating microorganisms into carbon biogeochemical models.

Agromyces chromiiresistens sp. nov., Novosphingobium album sp. nov., Sphingobium arseniciresistens sp. nov., Sphingomonas pollutisoli sp. nov., and Salinibacterium metalliresistens sp. nov.: five new members of Microbacteriaceae and Sphingomonadaceae from polluted soil.

There are many unidentified microbes in polluted soil needing to be explored and nominated to benefit the study of microbial ecology. In this study, a taxonomic research was carried out on five bacterial strains which were isolated and cultivated from polycyclic aromatic hydrocarbons, and heavy metals polluted soil of an abandoned coking plant. Phylogenetical analysis showed that they belonged to the phyla Proteobacteria and Actinobacteria, and their 16S rRNA gene sequence identities were lower than 98.5% to any known and validly nominated bacterial species, suggesting that they were potentially representing new species. Using polyphasic taxonomic approaches, the five strains were classified as new species of the families Microbacteriaceae and Sphingomonadaceae. Genome sizes of the five strains ranged from 3.07 to 6.60 Mb, with overall DNA G+C contents of 63.57-71.22 mol%. The five strains had average nucleotide identity of 72.38-87.38% and digital DNA-DNA hybridization of 14.0-34.2% comparing with their closely related type strains, which were all below the thresholds for species delineation, supporting these five strains as novel species. Based on the phylogenetic, phylogenomic, and phenotypic characterizations, the five novel species are proposed as Agromyces chromiiresistens (type strain H3Y2-19aT = CGMCC 1.61332T), Salinibacterium metalliresistens (type strain H3M29-4T = CGMCC 1.61335T), Novosphingobium album (type strain H3SJ31-1T = CGMCC 1.61329T), Sphingomonas pollutisoli (type strain H39-1-10T = CGMCC 1.61325T), and Sphingobium arseniciresistens (type strain H39-3-25T = CGMCC 1.61326T). Comparative genome analysis revealed that the species of the family Sphingomonadaceae represented by H39-1-10T, H39-3-25T, and H3SJ31-1T possessed more functional protein-coding genes for the degradation of aromatic pollutants than the species of the family Microbacteriaceae represented by H3Y2-19aT and H3M29-4T. Furthermore, their capacities of resisting heavy metals and metabolizing aromatic compounds were investigated. The results indicated that strains H3Y2-19aT and H39-3-25T were robustly resistant to chromate (VI) and/or arsenite (III). Strains H39-1-10T and H39-3-25T grew on aromatic compounds, including naphthalene, as carbon sources even in the presence of chromate (VI) and arsenite (III). These features reflected their adaptation to the polluted soil environment.

Identification of Triazolo-quinazolinone Derivatives as Novel and Potent Chitinase OfChi-h Inhibitors Based on Structure-Based Virtual Screening.

Insect chitinase, OfChi-h, from Ostrinia furnacalis, is considered as a promising target for the development of green pesticides. On the basis of the crystal structure of OfChi-h, we successfully obtained a triazolo-quinazolinone scaffold as the novel class of OfChi-h inhibitor via a structure-based virtual screening approach. Rational compound screening enabled us to acquire a potent OfChi-h inhibitor TQ19 with a Ki value of 0.33 µM. Furthermore, the in vivo biological activity of target compounds was assayed. The results showed that compounds TQ8 and TQ19 could dramatically inhibit the growth and development of Ostrinia nubilalis larvae, and most of the compounds showed higher insecticidal activity than hexaflumuron. This present work reveals that triazolo-quinazolinone derivatives can serve as novel candidates for insect growth regulators.