Retinal neovascularization (RNV) is primarily driven by vascular endothelial growth factor (VEGF). However, current anti-VEGF therapies are limited by short half-lives and repeated injections, which reduce patient quality of life and increase medical risks. Additionally, not all patients benefit from anti-VEGF monotherapy, and some problems, such as unsatisfactory vision recovery, persist after long-term treatment. In this study, we constructed a recombinant adeno-associated virus (AAV), AAV2-SPLTH, which encodes an anti-VEGF antibody similar to bevacizumab, and assessed its effects in a doxycycline-induced Tet-opsin-VEGFA mouse model of RNV. AAV2-SPLTH effectively inhibited retinal leakage, RNV progression, and photoreceptor apoptosis in a Tet-opsin-VEGF mouse model. However, proteomic sequencing showed that AAV2-SPLTH failed to rescue the expression of phototransduction-related genes, which corresponded to reduced photoreceptor cell numbers. This study suggests that anti-VEGF monotherapy can significantly inhibit RNV to some extent but may not be enough to save visual function in the long term.
X-linked retinoschisis (XLRS) is a monogenic recessive inherited retinal disease which clinically manifests retinal schisis cavities and disproportionate reduction of b-wave amplitude to the a-wave amplitude. Currently there are no approved treatments while the causal agent was identified as the retinoschisin (RS1). In the last decade, gene therapy has got great progress and given hopes to incurable genetic diseases. Preclinical studies demonstrated the treatment benefits of hRS1 gene augmentation therapy in the mouse models. However, clinical outcomes are dissatisfied which may attribute to the dysfunctional assembly and/or the impaired targeted cells. In the preset study, the human synapsin 1 gene promoter (hSyn) was used to control the expression of hRS1 which specifically targets to the retinal ganglion cells and our results confirmed the specific expression and functional assembly. Moreover, our results demonstrated that a single intravitreal injection of rAAV2-hSyn-hRS1 results in architectural restoration of retinal schisis cavities, improvement of vision and well tolerance in the experimental XLRS mouse model. In brief, this study not only supports the clinical development of the rAAV2-hSyn-hRS1 vector in XLRS patients, but also confirms the therapeutic potential of rAAV-based gene therapy in inherited retinal diseases.
A method of internal pressure-temperature coupling analysis for the thermal decomposition of GFRP composites under high-temperature conditions was established, which incorporates coupled calculations of heat transfer equations, the Arrhenius equation, Darcy's law, and the ideal gas state equation. Using the overlapping mesh method, the coupling calculation of temperature and internal pressure is realized based on the UMATHT and USDFLD user subroutines developed. Specifically, two user subroutines, UMATHT-1 and UMATHT-2, are used to define the heat transfer equation and gas diffusion equation separately. Numerical simulations are conducted to simulate the polymers' thermal decomposition in high-temperature environments. For glass fiber/vinyl ester composites and glass fiber/phenolic composites, the predicted temperature and pressure values are in good agreement with experimental measurements, and porosity and permeability are then analyzed. Due to the accumulation of thermal decomposition gases, inter-pressure within the material surged and reached a peak value. After that, it began to decrease, but the factors affecting the pressure decrease vary at different positions. Specifically, the pressure closest to the heating surface is influenced by the combined effects of decomposition rate, permeability, and porosity, while the pressure far away from the heating surface is only affected by the initial permeability. The pressure in the intermediate region may be influenced by both increased porosity and initial permeability.
BACKGROUND: SIRPB1 expression is upregulated in various tumor types, including gliomas, and is known to contribute to tumor progression; nevertheless, its function in the immune milieu of gliomas is still mainly unknown. METHODS: This study, we analyzed 1152 normal samples from the GTEx database and 670 glioma samples from the TCGA database to investigate the relationship between the expression of SIRPB1 and clinicopathological features. Moreover, SIRPB1 gene knockout THP-1 cell lines were constructed using CRISPR/Cas9 and were induced into a co-culture of macrophages and glioma cells in vitro to learn more about the role of SIRPB1 in the glioma immune milieu. Lastly, we established a prognostic model to predict the effect of SIRPB1 on prognosis. RESULTS: Significantly higher levels of SIRPB1 expression were found in gliomas, which had an adverse effect on the immune milieu and correlated poorly with patient survival. SIRPB1 activation with certain antibodies results in SYK phosphorylation and the subsequent activation of calcium, MAPK, and NF-κB signaling pathways. This phenomenon is primarily observed in myeloid-derived cells as opposed to glioma cells. In vitro co-culture demonstrated that macrophages with SIRPB1 knockout showed decreased IL1RA, CCL2, and IL-8, which were recovered upon ectopic expression of SIRPB1 but reduced again following treatment with SYK inhibitor GS9973. Critically, a lower overall survival rate was linked to increased SIRPB1 expression. Making use of SIRPB1 expression along with additional clinicopathological variables, we established a nomogram that showed a high degree of prediction accuracy. CONCLUSIONS: Our study demonstrates that glioma cells can be activated by macrophages via SIRPB1, subsequently reprogramming the TME, suggesting that SIRPB1 could serve as a promising therapeutic target for gliomas.
Antibodies , Glioma , Humans , Calcium , Coculture Techniques , Computational Biology , Glioma/genetics , Syk Kinase/genetics , Tumor Microenvironment
Spinal cord injury (SCI) is a severe complication of spinal trauma with high disability and mortality rates. Effective therapeutic methods to alleviate neurobehavioural deficits in patients with SCI are still lacking. In this study, we established a spinal cord contusion (SCC) model in adult Sprague Dawley rats. Induced pluripotent stem cell-derived A2B5+ oligodendrocyte precursor cells (iP-A2B5+OPCs) were obtained from mouse embryonic fibroblasts and injected into the lesion sites of SCC rats. Serological testing and magnetic resonance imaging were employed to determine the effect of iP-A2B5+OPCs cell therapy. The Basso-Beattie-Bresnahan score and inclined plane test were performed on days 1, 3, 7, and 14 after cell transplantation, respectively. Differentially expressed long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) were detected by microarray analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to analyse the biological functions of these lncRNAs and mRNAs. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to verify variations in the expression of crucial target genes. The results demonstrated that induced pluripotent stem cells exhibited embryonic stem cell-like morphology and could differentiate into diverse neural cells dominated by oligodendrocytes. The neurobehavioural performance of rats treated with iP-A2B5+OPCs transplantation was better than that of rats with SCC without cell transplantation. Notably, we found that 22 lncRNAs and 42 mRNAs were concurrently altered after cell transplantation, and the key lncRNA (NR_037671) and target gene (Cntnap5a) were identified in the iP-A2B5+OPCs group. Moreover, RT-qPCR revealed that iP-A2B5+OPCs transplantation reversed the downregulation of NR_037671 induced by SCC. Our findings indicated that iP-A2B5+OPCs transplantation effectively improves neurological function recovery after SCC, and the mechanism might be related to alterations in the expression of lncRNAs and mRNAs, such as NR_037671 and Cntnap5a.
BACKGROUND: With the successful development of modern immunotherapy, immune checkpoint inhibitors (ICIs) are currently considered potential therapeutic options for patients with cancer. However, the therapeutic potential of ICIs in human cancer is mainly limited by their systemic toxicity and low response rate, which suggests the necessity of local drug delivery with an effective vector and reshaping the immunosuppressive tumor microenvironment (TME) to enhance ICI therapy. Here, we constructed a novel double-gene recombinant oncolytic adenovirus named RCAd-LTH-shPD-L1 based on the RCAd virus platform armed with a DNA fragment encoding an anti-VEGF antibody and shRNA to inhibit PD-L1 expression. METHODS: The correct assembly of RCAd-LTH-shPD-L1 was characterized by analyzing its secretion, antigen specificity, and replication using western blotting, ELISA and quantitative PCR, respectively. The in vitro effects of RCAd-LTH-shPD-L1 on cell proliferation, vasculogenic, and cell migration were assessed. Antitumor effects and therapeutic mechanisms were evaluated in vivo using immunodeficient and humanized immune system mouse models. The TME was studied by ELISA, immunohistochemistry and flow cytometry. RESULTS: RCAd-LTH-shPD-L1 cells secreted anti-VEGF antibodies and inhibited the expression of PD-L1 in cancer cells. Moreover, RCAd-LTH-shPD-L1 exerted a specific cytotoxic effect on human cancer cells, but not on murine cancer cells or normal human cells. RCAd-LTH-shPD-L1 elicited a more potent antitumor effect in an immunodeficient mouse model and a humanized immune system mouse model than RCAd-shPD-L1, as demonstrated by the significant decrease in tumor growth. Furthermore, RCAd-LTH-shPD-L1 modulated the TME, which led to lymphocyte infiltration and alteration of their immune phenotype, as characterized by downregulation of anoxic factor HIF-1α and angiogenesis marker CD31, upregulation of cytokine such as IFN-γ, IL-6 and IL-12. CONCLUSIONS: In summary, our data demonstrated that the localized delivery of anti-VEGF antibodies and shPD-L1 by engineered RCAd-LTH-shPD-L1 is a highly effective and safe strategy for cancer immunotherapy. Moreover, the data underscore the potential of combining local virotherapy and anti-angiogenic therapy with ICIs as an effective TME therapy for poorly infiltrating tumors.
B7-H1 Antigen , Neoplasms , Humans , Animals , Mice , B7-H1 Antigen/metabolism , Adenoviridae/genetics , Adenoviridae/metabolism , Tumor Microenvironment , Neoplasms/therapy , Neoplasms/metabolism , Disease Models, Animal , Lymphocytes/metabolism
[This corrects the article DOI: 10.3389/fmicb.2022.1034816.].
Atypical teratoid/rhabdoid tumours (AT/RTs) are rare central nervous system neoplasms that frequently occur in infants and children and have a very poor prognosis. In recent years, molecular analysis of AT/RTs has shown that biallelic inactivation of SMARCB1 (INI1, SNF5, BAF47) or SMARCA4 (BRG1) frequently occurs. Here, we present a case of basal ganglia AT/RT with SMARCB1 gene deficiency and CDK6 gene amplification in a 5-year-old child. A 5-year-old boy was hospitalized due to a 1-week history of frontal and parietal headache. Magnetic resonance imaging (MRI) demonstrated a 3â cm × 2â cm × 1.5â cm heterogeneous enhanced mass located at the right basal ganglia that partially protruded into the right lateral ventricle. The lesion was successfully resected under electrophysiological monitoring and neuronavigation. The postoperative pathological examination implied an AT/RT diagnosis, with loss of SMARCB1 protein, SMARCB1 gene deficiency and CDK6 gene amplification. Unfortunately, the patient died due to respiratory and circulatory failure at 5 weeks after the operation. To date, standard regimens have not yet been established due to the lack of large-scale prospective studies for AT/RT. The p16-RB signalling pathway should be considered as a potential target for AT/RT treatment modalities. Apart from traditional regimens, targeted therapies, especially CDK4/6 inhibitors, are likely a promising therapeutic option for AT/RT treatment.
Glioblastoma (GBM) is a malignant brain cancer refractory to the current standard of care, prompting an extensive search for novel strategies to improve outcomes. One approach under investigation is oncolytic virus (OV) therapy in combination with radiotherapy. In addition to the direct cytocidal effects of radiotherapy, radiation induces cellular senescence in GBM cells. Senescent cells cease proliferation but remain viable and are implicated in promoting tumor progression. The interaction of viruses with senescent cells is nuanced; some viruses exploit the senescent state to their benefit, while others are hampered, indicating senescence-associated antiviral activity. It is unknown how radiation-induced cellular senescence may impact the oncolytic properties of OVs based on the vaccinia virus (VACV) that are used in combination with radiotherapy. To better understand this, we induced cellular senescence by treating GBM cells with radiation, and then evaluated the growth kinetics, infectivity, and cytotoxicity of an oncolytic VACV, ∆F4LΔJ2R, as well as wild-type VACV in irradiated senescence-enriched and non-irradiated human GBM cell lines. Our results show that both viruses display attenuated oncolytic activities in irradiated senescence-enriched GBM cell populations compared to non-irradiated controls. These findings indicate that radiation-induced cellular senescence is associated with antiviral activity and highlight important considerations for the combination of VACV-based oncolytic therapies with senescence-inducing agents such as radiotherapy.
Rechargeable aqueous ion batteries (AIBs) play essential roles in the increasing demand for high-performance energy storage systems, and yet they are hampered by the lack of suitable cathode materials because of the sluggish intercalation kinetics. In this work, we develop an effective and feasible strategy to enhance the performance of AIBs by broadening the interlayer spacing by using intercalated CO2 molecules to promote the intercalation kinetics by using first principles simulations. Compared with pristine MoS2, the intercalation of CO2 molecules with a 3/4 ML coverage significantly increases the interlayer spacing to 9.383 Å from 6.369 Å and the diffusivity is boosted by 12 orders of magnitude for Zn ions, 13 orders for Mg ions and one order for Li ions. Moreover, the concentrations of intercalating Zn, Mg and Li ions are enhanced by 7, 1 and 5 orders of magnitude, respectively. The significantly increased diffusivity and intercalation concentration of metal ions signify that intercalating CO2 bilayer MoS2 is a promising cathode material to realize metal ion batteries with a rapid charging capability and high storage capacity. The strategy developed in this work can be generally applied to increase the metal ion storage capacity in transition metal dichalcogenide (TMD)- and other layered material-based cathodes and make them promising for next-generation rapidly rechargeable batteries.
Proficiency testing based on quality control materials is an important component of the quality assurance system for detection methods. However, in the detection of infectious diseases, it is a challenge to use quality control materials derived from clinical samples or pathogens owing to their infectious nature. The Xpert MTB/RIF assay, endorsed by the World Health Organization, is one of the most widely implemented assays in the detection of Mycobacterium tuberculosis along with rifampicin resistance and its heterogeneity. Clinical isolates are typically used as quality controls for this assay, leading to concerns about biosafety, constrained target sequence polymorphisms, and time-consuming preparation. In this study, a heterogeneous quality control library for the Xpert MTB/RIF assay was constructed based on DNA synthesis and site-directed mutation, which provides sufficient rifampicin resistance polymorphisms, enabling monitoring all five probes of Xpert MTB/RIF and its combinations. Escherichia coli and Bacillus subtilis were used as heterogeneous hosts rather than the pathogen itself to eliminate biosafety risks; thus, preparation does not require a biosafety level III laboratory and the production time is reduced from a few months to a few days. The panel was stable for more than 15 months stored at 4°C and could be distributed at room temperature. All 11 laboratories in Shanghai participating in a pilot survey identified the specimens with corresponding probe patterns, and discordant results highlighted inappropriate operations in the process. Collectively, we show, for the first time, that this library, based on heterogeneous hosts, is an appropriate alternative for M. tuberculosis detection.
Mycobacterium tuberculosis , Tuberculosis , Humans , Rifampin/pharmacology , Drug Resistance, Bacterial/genetics , Sensitivity and Specificity , China , Tuberculosis/diagnosis , Tuberculosis/microbiology , Mycobacterium tuberculosis/genetics , Quality Control
Glioblastoma (GB) is a malignant and immune-suppressed brain cancer that remains incurable despite the current standard of care. Radiotherapy is a mainstay of GB treatment, however invasive cancer cells outside the irradiated field and radioresistance preclude complete eradication of GB cells. Oncolytic virus therapy harnesses tumor-selective viruses to spread through and destroy tumors while stimulating antitumor immune responses, and thus has potential for use following radiotherapy. We demonstrate that oncolytic ΔF4LΔJ2R vaccinia virus (VACV) replicates in and induces cytotoxicity of irradiated brain tumor initiating cells in vitro. Importantly, a single 10 Gy dose of radiation combined with ΔF4LΔJ2R VACV produced considerably superior anticancer effects relative to either monotherapy when treating immune-competent orthotopic CT2A-luc mouse models-significantly extending survival and curing the majority of mice. Mice cured by the combination displayed significantly increased survival relative to naïve age-matched controls following intracranial tumor challenge, with some complete rejections. Further, the combination therapy was associated with an increased ratio of CD8+ effector T cells to regulatory T cells compared to either monotherapy. This study validates the use of radiation with an oncolytic ΔF4LΔJ2R VACV to improve treatment of this malignant brain cancer.
Brain Neoplasms , Glioblastoma , Oncolytic Virotherapy , Oncolytic Viruses , Mice , Animals , Oncolytic Viruses/physiology , Vaccinia virus/genetics , Glioblastoma/therapy , Brain Neoplasms/therapy , Xenograft Model Antitumor Assays , Cell Line, Tumor
Five Gram-stain-positive, aerobic, non-motile actinobacterial strains designated as CPCC 205763T, CPCC 203386T, CPCC 205716T, CPCC 203406T, and CPCC 203407 were obtained from different ecosystems associated with four kinds of Chinese traditional medicinal plants. The 16S rRNA gene sequences of these five strains showed closely related to members of the genus Herbiconiux of the family Microbacteriaceae, with the highest similarities of 97.4-99.7% to the four validly named species of Herbiconiux. In the phylogenetic trees based on 16S rRNA gene sequences and the core genome, these isolates clustered into the clade of the genus Herbiconiux within the lineage of the family Microbacteriaceae. The overall genome relatedness indexes (values of ANI and dDDH) and the phenotypic properties (morphological, physiological and chemotaxonomic characteristics) of these isolates, readily supported to affiliate them to the genus Herbiconiux, representing four novel species, with the isolates CPCC 203406T and CPCC 203407 being classified in the same species. For which the names Herbiconiux aconitum sp. nov. (type strain CPCC 205763T = I19A-01430T = CGMCC 1.60067T), Herbiconiux daphne sp. nov. (type strain CPCC 203386T = I10A-01569T = DSM 24546T = KCTC 19839T), Herbiconiux gentiana sp. nov. (type strain CPCC 205716T = I21A-01427T = CGMCC 1.60064T), and Herbiconiux oxytropis sp. nov. (type strain CPCC 203406T = I10A-02268T = DSM 24549T = KCTC 19840T) were proposed, respectively. In the genomes of these five strains, the putative encoding genes for amidase, endoglucanase, phosphatase, and superoxidative dismutase were retrieved, which were classified as biosynthetic genes/gene-clusters regarding plant growth-promotion (PGP) functions. The positive results from IAA-producing, cellulose-degrading and anti-oxidation experiments further approved their potential PGP bio-functions. Pangenome analysis of the genus Herbiconiux supported the polyphasic taxonomy results and confirmed their bio-function potential.
Increasing evidence suggests that targeting ubiquitin-specific peptidase 8 (USP8) serves as an attractive anti-cancer strategy. However, the role of USP8 inhibitor, DUB-IN-1, in esophageal squamous cell carcinoma (ESCC) cells still needs to be explored. Here, immunohistochemistry was employed to examine the expression of USP8 in ESCC tissues. Cell Counting Kit-8 (CCK-8) was used to evaluate cell proliferation ability, and propidium iodide (PI) was selected to test the effect of DUB-IN-1 on cell cycle. AnnexinV-FITC/PI staining and the activity of caspase 3 were detedcted to evaluate apoptosis. Transmission electron microscope, microtubule-associated protein 1 light-chain 3 (LC3) expression, and acridine orange (AO) staining were selected to check if there was autophagy. Comet assay and γ-H2AX immunofluorescence was used to monitor DNA damage. Rescue experiment was used to determine the key role of of p53 in cell cycle, apoptosis, and autophagy. Results revealed that the leve of USP8 was higher in ESCC tissues than that in tissues adjacent to carcinoma. DUB-IN-1, an USP8 inhibitor, caused DNA damage, led to G2/M phase block by p53-p21 axis, and triggered apoptosis by regulating the p53 target proteins including Bax, Noxa, and Puma. Besides, DUB-IN-1 could stimulate autophagy through p53-dependent adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) activation. Taken together, this study revealed the cytotoxic effects and the mechanism of DUB-IN-1, which indicated that DUB-IN-1 may be a novel inhibitor targeting USP8 that can kill ESCC cells. USP8 inhibitor, DUB-IN-1, treatment could inhibit esophageal squamous cell carcinoma cell growth and induce G2/M cell cycle arrest, apoptosis, and autophagy by DNA damage-induced p53 activation. DUB-IN-1 treatment led to G2/M cell cycle arrest by upregulating the protein level of p21 and triggered apoptosis by modulating the p53 target proteins including Bax, Noxa, and Puma. Meanwhile, DUB-IN-1 treatment stimulated protective autophagy through p53-dependent AMPK activation. Collectively, these findings suggested that DNA damage-triggered p53 activation, p53-Puma/Noxa/Bax, p53-p21, and p53-AMPK pathways were all involved in the effect of DUB-IN-1.
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Tumor Suppressor Protein p53/metabolism , Apoptosis Regulatory Proteins/genetics , Apoptosis Regulatory Proteins/metabolism , Apoptosis Regulatory Proteins/pharmacology , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/pathology , bcl-2-Associated X Protein/metabolism , AMP-Activated Protein Kinases/metabolism , Cell Line, Tumor , Cell Cycle Checkpoints , Apoptosis , DNA Damage , Cell Proliferation , G2 Phase Cell Cycle Checkpoints , Autophagy , Endopeptidases/genetics , Endopeptidases/metabolism , Endopeptidases/pharmacology
[This corrects the article DOI: 10.3389/fmicb.2023.1119226.].
Two Gram-staining negative strains (CPCC 101082T and CPCC 101083T) were isolated from biological sandy soil crusts samples collected from Badain Jaran desert, China. Both isolates were heterotrophic phototroph, could produce indole-3-acetic acid. The 16S rRNA gene sequences of these two strains were closely related to the members of the family Geminicoccaceae, showing high similarities with Geminicoccus roseus DSM 18922T (96.9%) and Arboricoccus pini B29T1T (90.1%), respectively. In phylogenetic tree based on 16S rRNA gene sequences, strain CPCC 101082T and CPCC 101083T formed a robust distinct clade with Geminicoccus roseus DSM 18922T within the family Geminicoccaceae, which indicated that these two isolates could be classified into the genus Geminicoccus. The growth of strain CPCC 101082T occurred at 15-42°C and pH 4.0-10.0 (optima at 28-37°C and pH 6.0-8.0). The growth of strain CPCC 101083T occurred at 4-45°C and pH 4.0-10.0 (optima at 25-30°C and pH 6.0-8.0). The major cellular fatty acids of CPCC 101082T and CPCC 101083T contained C18:1 ω7c/C18:1 ω6c, cyclo-C19:0 ω8c, and C16:0. Q-10 was detected as the sole respiratory quinone. Diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, an unidentified phospholipid and an unidentified aminolipid were tested in the polar lipids profile. The genomes of the two isolates were characterized as about 5.9 Mbp in size with the G + C content of nearly 68%. The IAA-producing encoding genes were predicated in both genomes. The values of average nucleotide identity were 80.6, 81.2 and 92.4% based on a pairwise comparison of the genomes of strains CPCC 101082T and CPCC 101083T and Geminicoccus roseus DSM 18922T, respectively. On the basis of the genotypic, chemotaxonomic and phenotypic characteristics, the strains CPCC 101082T (=NBRC 113513T = KCTC 62853T) and CPCC 101083T (=NBRC 113514T = KCTC 62854T) are proposed to represent two novel species of the genus Geminicoccus with the names Geminicoccus flavidas sp. nov. and Geminicoccus harenae sp. nov.
Stenotrophomonas spp. have primarily been reported as non-pathogenic, plant-probiotic bacteria, despite the presence of some opportunistic human pathogens in the genus. Here, three Gram-stain negative, rod-shaped, non-spore-forming bacteria, designated as strains CPCC 101365T, CPCC 101269T, and CPCC 101426 were isolated from surface-sterilized medicinal plant roots of a mulberry plant in Chuxiong of the Yunnan Province, freshwater from Erhai Lake in the Yunnan Province, and sandy soils in the Badain Jaran desert in Inner Mongolia Autonomous Region, China, respectively. The 16S rRNA gene sequences analysis of these isolates in comparison with sequences from the GenBank database indicated that they belong to the genus Stenotrophomonas, with nucleotide similarities of 96.52-99.92% to identified Stenotrophomonas members. Phylogenetic analysis based on 16S rRNA gene and genome sequences confirmed that the isolates are members of the genus Stenotrophomonas. Values for genomic average nucleotide identity (ANI; <95%) and digital DNA-DNA hybridization (dDDH; < 70%) indicated that strains CPCC 101365T and CPCC 101269T were well-differentiated from validly described Stenotrophomonas species, while strain CPCC 101426 shared high ANI (97.7%) and dDDH (78.3%) identity with its closest phylogenetic neighbor, Stenotrophomonas koreensis JCM 13256T. The three genomes were approximately 3.1-4.0 Mbp in size and their G + C content ranged in 66.2-70.2%, with values slightly differing between CPCC 101365T (3.4 Mbp; 70.2%), CPCC 101269T (4.0 Mbp; 66.4%), and CPCC 101426 (3.1 Mbp; 66.2%). Genes encoding enzymes involved in the biosynthesis of indole-3-acetic acid (IAA) and siderophores were identified in the genomes of the three isolates, suggesting that these strains might serve roles as plant-growth promoting microorganisms. The polar lipid fractions of the three isolates primarily comprised diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), and phosphatidylethanolamine (PE). The predominant cellular fatty acid was iso-C15: 0, with moderate amounts of antesio-C15: 0, iso-C11: 0, iso C17: 1 É·9c/C16: 0 10-methyl, iso-C14: 0, and C16: 1 É·7c/C16: 1 É·6c. These results indicated that polyphasic characteristics of strains CPCC 101365T and CPCC 101269T differed from other identified Stenotrophomonas species and that strain CPCC 101426 was affiliated with the species Stenotrophomonas koreensis. Accordingly, two novel species of the genus Stenotrophomonas were consequently proposed, corresponding to Stenotrophomonas mori sp. nov. (type strain CPCC 101365T = DY006T = KCTC 82900T) and Stenotrophomonas lacuserhaii sp. nov. (type strain CPCC 101269T = K32T = KCTC 82901T). Highlights: Members of the genus Stenotrophomonas, and particularly Stenotrophomonas maltophilia, are opportunistic human pathogens, but not enough research has evaluated the identification of environmental Stenotrophomonas spp. However, most Stenotrophomonas spp. serves as plant-probiotic bacteria.In this study, we obtained and characterized three Stenotrophomonas strains from different ecosystems. Based on phenotypic differences, chemotaxonomic properties, ANI and dDDH identity values, and phylogenetic analyses, two novel Stenotrophomonas species are proposed for the strains identified here. The encoding genes related to plant-growth promotion in the genomes of the newly recovered Stenotrophomonas spp. were retrieved. Follow-on experiments confirmed that these strains produced the important plant hormone IAA. Thus, these Stenotrophomonas spp. could considerably contribute to shaping and maintaining ecological stability in plant-associated environments, particularly while acting as plant-probiotic microorganisms.
Organic-inorganic perovskites face the issues of being vulnerable to oxygen and moisture and the trap sites located at the surface and grain boundaries. Integration of two-dimensional (2D) perovskites as a capping layer is an effective route to enhance both photovoltaic efficiency and environmental stability of the three-dimensional (3D) underlayer. Here, we employ 1,4-butanediammonium diiodide (BDADI), which has a short chain length and diammonium cations, to construct a 3D/2D stacking perovskite solar cells (PSCs). The introduction of BDA2+ could passivate surface defects in 3D perovskites by forming 2D Dion-Jacobson (DJ) phase perovskites and effectively suppressing nonradiative recombination, thus resulting in a longer carrier lifetime. The DJ 2D capping layer also regulate the energy level arrangement, enabling a better charge extraction and transport process. In addition, the water-resistance ability of 3D perovskite gets improved because of the hydrophobic characteristic of 1,4-butanediammonium cations. Consequently, the 3D/2D stacking PSCs yield an energy conversion efficiency of 20.32% in company with the enhanced long-term stability.
The neuroinflammatory pathway regulated by nuclear factor kappa-B (NF-κB) plays an important role in the occurrence, development, and prognosis of poststroke depression (PSD). The regulatory effect of the traditional Chinese medicine compound Xingnao Jieyu decoction (XNJY) on the NF-κB pathway of PSD is still unclear. This study aimed to observe the effect of XNJY on PSD and explore the molecular mechanism of its intervention in the NF-κB pathway. Middle cerebral artery occlusion (MCAO) and chronic unpredictable mild stress were used to establish a PSD rat model. Body mass measurement, behavioral testing, Nissl staining, ELISA, and Western blot were also performed. XNJY and fluoxetine hydrochloride (Flu) treatment of PSD model rats showed significant antidepressant effects. XNJY and Flu treatment could reduce cortical and hippocampal neuronal damage. XNJY reduced inflammation and restored the levels of IL-4, IL-10, and BDNF. In addition, XNJY showed a significant regulatory effect on the NF-κB pathway and the expression of synapse-related proteins PSD-95 and SYN. These results showed that XNJY could significantly reduce the depressive symptoms of PSD rats, and this reduction may be related to the regulation of the NF-κB signaling pathway to improve neuroinflammation and synaptic function.
For carbon fiber epoxy resin used in aerostructure, thermal degradation mechanism and kinetics play an important role in the evaluation of thermal response and combustion characteristics. However, the thermal decomposition process and mechanism are difficult to unify strictly due to the complexity of the components from different suppliers. In the present study, a product of carbon fiber epoxy resin made by AVIC (Aviation Industry Corporation of China) composite corporation is examined to identify its thermal degradation mechanism and pyrolysis products by measurements, including simultaneous thermal analysis, Fourier transform infrared spectroscopy and mass spectrometry, establish the kinetic model by Kissinger/Friedman/Ozawa/Coats-Redfern methods. The results show thermal degradation occurs in three steps under the inert atmosphere, but in four steps under air atmosphere, respectively. The first two steps in both environments are almost the same, including drying, carbon dioxide escape and decomposition of the epoxy resin. In the third step of inert atmosphere, phenol is formed, methane decreases, carbon monoxide basically disappears and carbon dioxide production increases. However, in air, thermal oxidation of the carbonaceous residues and intermolecular carbonization are observed. Furthermore, thermal degradation reaction mechanism submits to the F4 model. These results provide fundamental and comprehensive support for the application of carbon fiber epoxy resin in aircraft industry.
