SIRPB1 regulates inflammatory factor expression in the glioma microenvironment via SYK: functional and bioinformatics insights.

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.

USP8 inhibitor-induced DNA damage activates cell cycle arrest, apoptosis, and autophagy in esophageal squamous cell carcinoma.

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.

CXCL12 Regulates the Cholinergic Locus and CHT1 Through Akt Signaling Pathway.

BACKGROUND: CXCL12 is pivotal for cholinergic neurons, and it induces the expressions of several genes that are essential for synthesis and storage of acetylcholine(ACh), specifically choline acetyltransferase, vesicular ACh transporter (VAChT), and choline transporter. The present study explored the impact of pharmacological Akt inhibition upon cholinergic gene expression. METHODS: Western blotting was employed to determine the level of p-AKT, RT-PCR to check the mRNA levels of and CHT1(choline transporter1),VAChT and ChAT, ELISA to decipher the secretion of ACh and the activity of choline acetyltransferase. RESULTS: Here we demonstrated, in the rat pheochromocytoma cell line PC12 and in primary rat neuronal cultures, that CXCL12-evoked up-regulation of CHT1, VAChT and ChAT was mediated by Akt. Inhibition of Akt by the pharmacological inhibitor GSK690693 eliminated CXCL12-stimulated increases in cholinergic gene expression. Moreover, treatment with GSK690693 reversed CXCL12-evoked increases in choline acetyltransferase activity and ACh production. CONCLUSION: Our results suggest that CXCL12 contributes to cholinergic gene expression via Akt signaling pathway.

Effects of delayed motherhood on hippocampal gene expression in offspring rats.

While many studies have examined the pregnancy and health-related outcomes of delayed motherhood for women, less is known concerning the potential consequences for their children. This study aims to investigate the effect of delayed motherhood on the hippocampus at the whole genome level. Sprague-Dawley rat females, either at the age of 3 or 12 months, were individually housed with a randomly selected 3-month-old male. The rat whole genome expression chips were used to detect gene expression differences in the hippocampus of newborn rats. The gene expression profile was studied through gene ontology and signal pathway analyses. qRT-PCR was used to determine the mRNA expression of solute carrier family 2 (SLC2A1) and S-phase kinase-associated protein 2 (SKP2). Western blot was used to detect the protein expression of SKP2. Compared to the control group, 1291 differentially expressed genes were detected, including 635 up-regulated genes and 656 down-regulated genes. These differential expressed genes were involved in 110 significant biological process and nine significant signaling pathways, in which the pathway in cancer is the most changed pathway. For SKP2 (up-regulated) and SLC2A1 (up-regulated) genes which were relevant to the pathway in cancer, qRT-PCR results were consistent with gene chip assay results. The upregulation of SKP2 was also demonstrated at protein level. In conclusion, delayed motherhood led to unique patterns of hippocampal gene expression in offspring and the newly identified genes afford a quantitative view of the changes which enable deeper insights into the molecular basis underlying the role of delayed motherhood.

[System Design of a Medical Constnt Temperature Flushing Pump].

The flushing pump which is applied to clean operative wound has no temperature controlling function up to now, and doctors have to prepare the flushing fluid that has previously been warmed. The flushing pump system with medical constant temperature designed in our laboratory can absorb flushing fluid at the room temperature, and then eject flushing fluid with the temperature in accordance with the requirements of operations at a controlled constant flow rate. The system combines flow rate control with temperature control functions. The flushing pump system includes flushing part, temperature controlling part, key inputting part, liquid crystal displaying part and exceptional situation monitoring part. The present paper introduces the design method and principle of each part of the system at first, and then gives the debug method of all the system parameters. Finally the paper discusses the performance of the system according to the result of the experiment.

Lacking chloroplasts in guard cells of crumpled leaf attenuates stomatal opening: both guard cell chloroplasts and mesophyll contribute to guard cell ATP levels.

Controversies regarding the function of guard cell chloroplasts and the contribution of mesophyll in stomatal movements have persisted for several decades. Here, by comparing the stomatal opening of guard cells with (crl-ch) or without chloroplasts (crl-no ch) in one epidermis of crl (crumpled leaf) mutant in Arabidopsis, we showed that stomatal apertures of crl-no ch were approximately 65-70% those of crl-ch and approximately 50-60% those of wild type. The weakened stomatal opening in crl-no ch could be partially restored by imposing lower extracellular pH. Correspondingly, the external pH changes and K(+) accumulations following fusicoccin (FC) treatment were greatly reduced in the guard cells of crl-no ch compared with crl-ch and wild type. Determination of the relative ATP levels in individual cells showed that crl-no ch guard cells contained considerably lower levels of ATP than did crl-ch and wild type after 2 h of white light illumination. In addition, guard cell ATP levels were lower in the epidermis than in leaves, which is consistent with the observed weaker stomatal opening response to white light in the epidermis than in leaves. These results provide evidence that both guard cell chloroplasts and mesophyll contribute to the ATP source for H(+) extrusion by guard cells.

[Design of the temperature control system for the thermostatic medical infusion pump].

In surgery operations, wound should be cleaned with warm sterilized saline solution. In order to reach rapidly warming the washing solution from the room temperature during the surgery, we designed a thermostatic medical infusion pump. The present paper mainly presents researches on the two temperature control methods in the standby mode and in the flushing mode of the system. In the standby mode, the traditional proportional-integral-derivative (PID) control algorithm was adopted. In the flushing mode, dynamic characteristics of the system was changed in real time, which made the thermostatic control process more complex, and the fitted control function combined with the PID control algorithm was adopted in this mode. The temperature control parameters were adjusted in real time according to the initial temperature and the flow rate of the washing solution to obtain a constant temperature of the washing solution, no matter how the initial temperature and the flow rate are changed. The experiment results showed that this kind of control system performed well with a high accuracy.

Internal Pressure-Temperature Coupling Analysis Method for Thermal Decomposition of GFRP Composites Based on the Overlapping Elements Method.

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.

Intravitreal Delivery of rAAV2-hSyn-hRS1 Results in Retinal Ganglion Cell-Specific Gene Expression and Retinal Improvement in the Rs1-KO Mouse.

X-linked retinoschisis (XLRS) is a monogenic recessive inherited retinal disease caused by defects in retinoschisin (RS1). It manifests clinically as retinal schisis cavities and a disproportionate reduction of b-wave amplitude compared with the a-wave amplitude. Currently there is no approved treatment. In the last decade, there has been major progress in the development of gene therapy for XLRS. Previous preclinical studies have demonstrated the treatment benefits of hRS1 gene augmentation therapy in mouse models. However, outcomes in clinical trials have been disappointing, and this might be attributed to dysfunctional assembly of RS1 complexes and/or the impaired targeted cells. In this study, the human synapsin 1 gene promoter (hSyn) was used to control the expression of hRS1 to specifically target retinal ganglion cells and our results confirmed the specific expression and functional assembly of the protein. Moreover, our results demonstrated that a single intravitreal injection of rAAV2-hSyn-hRS1 results in architectural restoration of retinal schisis cavities and improvement in vision in a mouse model of XLRS. 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.

RCAd-LTH-shPD-L1, a double-gene recombinant oncolytic adenovirus with enhanced antitumor immunity, increases lymphocyte infiltration and reshapes the tumor microenvironment.

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.

Inefficacy of anti-VEGF therapy reflected in VEGF-mediated photoreceptor degeneration.

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.

Microarray analysis of lncRNAs and mRNAs in spinal cord contusion rats with iPSC-derived A2B5+ oligodendrocyte precursor cells transplantation.

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.

Construction and application of a heterogeneous quality control library for the Xpert MTB/RIF assay in tuberculosis diagnosis.

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.

Molecular engineering on a MoS2 interlayer for high-capacity and rapid-charging aqueous ion batteries.

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.

Atypical teratoid/rhabdoid tumour with CDK6 amplification in a child: a case report and literature review.

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 3 cm × 2 cm × 1.5 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.

Radiation-Induced Cellular Senescence Reduces Susceptibility of Glioblastoma Cells to Oncolytic Vaccinia Virus.

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.

Pangenome analysis of the genus Herbiconiux and proposal of four new species associated with Chinese medicinal plants.

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.

Corrigendum: Geminicoccus flavidas sp. nov. and Geminicoccus harenae sp. nov., two IAA-producing novel rare bacterial species inhabiting desert biological soil crusts.

[This corrects the article DOI: 10.3389/fmicb.2022.1034816.].

Corrigendum: Pangenome analysis of the genus Herbiconiux and proposal of four new species associated with Chinese medicinal plants.

[This corrects the article DOI: 10.3389/fmicb.2023.1119226.].

Radiation combined with oncolytic vaccinia virus provides pronounced antitumor efficacy and induces immune protection in an aggressive glioblastoma model.

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.