PCV2 targets cGAS to inhibit type I interferon induction to promote other DNA virus infection.

Viruses use diverse strategies to impair the antiviral immunity of host in order to promote infection and pathogenesis. Herein, we found that PCV2 infection promotes the infection of DNA viruses through inhibiting IFN-ß induction in vivo and in vitro. In the early phase of infection, PCV2 promotes the phosphorylation of cGAS at S278 via activation of PI3K/Akt signaling, which directly silences the catalytic activity of cGAS. Subsequently, phosphorylation of cGAS at S278 can facilitate the K48-linked poly-ubiquitination of cGAS at K389, which can been served as a signal for recognizing by the ubiquitin-binding domain of histone deacetylase 6 (HDAC6), to promote the translocation of K48-ubiquitinated-cGAS from cytosol to autolysosome depending on the deacetylase activity of HDAC6, thereby eventually resulting in a markedly increased cGAS degradation in PCV2 infection-induced autophagic cells relative to Earle's Balanced Salt Solution (EBSS)-induced autophagic cells (a typical starving autophagy). Importantly, we found that PCV2 Cap and its binding protein gC1qR act as predominant regulators to promote porcine cGAS phosphorylation and HDAC6 activation through mediating PI3K/AKT signaling and PKCδ signaling activation. Based on this finding, gC1qR-binding activity deficient PCV2 mutant (PCV2RmA) indeed shows a weakened inhibitory effect on IFN-ß induction and a weaker boost effect for other DNA viruses infection compared to wild-type PCV2. Collectively, our findings illuminate a systematic regulation mechanism by which porcine circovirus counteracts the cGAS-STING signaling pathway to inhibit the type I interferon induction and promote DNA virus infection, and identify gC1qR as an important regulator for the immunosuppression induced by PCV2.

Cellular p32 Is a Critical Regulator of Porcine Circovirus Type 2 Nuclear Egress.

Circoviruses are the smallest DNA viruses known to infect mammalian and avian species. Although circoviruses are known to be associated with a range of clinical diseases, the details of circovirus DNA release still remain unknown. Here, we identified p32 as a key regulator for porcine circoviral nuclear egress. Upon porcine circovirus type 2 (PCV2) infection, p32 was recruited into the nucleus by the viral capsid (Cap) protein; simultaneously, protein kinase C isoform δ (PKC-δ) was phosphorylated at threonine 505 by phospholipase C (PLC)-mediated signaling at the early stage of infection, which was further amplified by Jun N-terminal protein kinase (JNK) and extracellular signal-regulated kinase (ERK) signaling at the late infection phase. p32 functioned as an adaptor to recruit phosphorylated PKC-δ and Cap to the nuclear membrane to phosphorylate lamin A/C, resulting in a rearrangement of nuclear lamina and thus facilitating viral nuclear egress. Consistent with these findings, knockout (KO) of p32 in PCV2-infected cells markedly reduced the phosphorylation of PKC-δ and impeded the recruitment of p-PKC-δ and Cap to the nuclear membrane, hence abolishing the phosphorylation of lamin A/C and the rearrangement of nuclear lamina. As a result, p32 depletion profoundly impaired the production of cell-free viruses during PCV2 infection. We further identified the N-terminal 24RRR26 of Cap to be crucial for binding to p32, and mutation of these three arginine residues significantly weakened the replication and pathogenesis of PCV2 in vivo In summary, our findings highlight a critical role of p32 in the activation and recruitment of PKC-δ to phosphorylate lamin A/C and facilitate porcine circoviral nuclear egress, and they certainly help understanding of the mechanism of PCV2 replication.IMPORTANCE Circovirus infections are highly prevalent in mammalian and avian species. Circoviral capsid protein is the only structural protein of the virion that plays an essential role in viral assembly. However, the machinery of circovirus nuclear egress is currently unknown. In this work, we identified p32 as a key regulator of porcine circovirus type 2 (PCV2) nuclear egress that forms a complex with the viral capsid (Cap) protein to enhance protein kinase C isoform δ (PKC-δ) activity; this resulted in a recruitment of phosphorylated PKC-δ to the nuclear membrane, which further phosphorylates lamin A/C to promote the rearrangement of nuclear lamina and facilitate viral nuclear egress. Notably, we found that the N-terminal 24RRR26 of Cap, a highly conserved motif among circovirus species, was required for interacting with p32, and that mutation of this motif markedly impeded PCV2 nuclear egress. These data indicate that p32 is a critical regulator of PCV2 nuclear egress and reveal the importance of this finding in circovirus replication.

Porcine DNAJB6 promotes PCV2 replication via enhancing the formation of autophagy in host cells.

Hsp40/DnaJ family proteins play important roles in the infection process of various viruses. Porcine DNAJB6 (pDNAJB6) is a major member of this family, but its role in modulating the replication of porcine circovirus type 2 (PCV2) is still unclear. In the present study, pDNAJB6 was found to be significantly upregulated by PCV2 infection, and confirmed to be interacted with PCV2 capsid (Cap) protein and co-localized at both cytoplasm and nucleus in the PCV2-infected cells. Knockout of pDNAJB6 significantly reduced the formation of autophagosomes in PCV2-infected cells or in the cells expressing Cap protein, whereas overexpression of pDNAJB6 showed an opposite effect. In addition, the domain mapping assay showed that the J domain of pDNAJB6 (amino acids (aa) 1-99) and the C terminus of Cap (162-234 aa) were required for the interaction of pDNAJB6 with Cap. Notably, the interaction of pDNAJB6 with Cap was very important to promoting the formation of autophagosomes induced by PCV2 infection or Cap expression and enhancing the replication of PCV2. Taken together, the results presented here show a novel function of pDNAJB6 in regulation of porcine circovirus replication that pDNAJB6 enhances the formation of autophagy to promote viral replication through interacting with viral capsid protein during PCV2 infection.

Porcine Circovirus Type 2 Suppresses IL-12p40 Induction via Capsid/gC1qR-Mediated MicroRNAs and Signalings.

Porcine circovirus (PCV) type 2 (PCV2), an immunosuppression pathogen, is often found to increase the risk of other pathogenic infections. Yet the relative immune mechanisms determining the susceptibility of PCV2-infected animals remain unclear. In this study, we confirmed that PCV2 infection suppressed IL-12p40 expression and host Th1 immune response, leading to a weakened pathogenic clearance upon porcine reproductive respiratory syndrome virus (PRRSV) or Haemophilus parasuis infection. PCV2 infection suppressed pathogens, LPS/IFN-γ, or LPS/R848-induced IL-12p40 expression in porcine alveolar macrophages. PCV2 capsid (Cap) was the major component to suppress IL-12p40 induction by LPS/IFN-γ, LPS/R848, PRRSV, or H. parasuis Either wild-type PCV2 or mutants PCV2-replicase 1 and PCV type 1-Cap2, which contained PCV2 Cap, significantly decreased IL-12p40 levels and increased the replication of PRRSV and H. parasuis in the lung tissues relative to mock or PCV type 1 infection. gC1qR, a Cap binding protein, was not involved in IL-12p40 induction but mediated the inhibitory effect of PCV2 Cap on IL-12p40 induction. PCV2 also activated PI3K/Akt1 and p38 MAPK signalings to inhibit IL-12p40 expression via inhibition of NF-κB p65 binding to il12B promoter and upregulation of miR-23a and miR-29b. Knockdown of Akt1 and p38 MAPK downregulated miR-23a and miR-29b and increased IL-12p40 expression. Inhibition of miR-23a and miR-29b attenuated the inhibitory effect of PCV2 on IL-12p40 induction, resulting in an increased IL-12p40 expression and Th1 cell population and reduced susceptibility to PRRSV or H. parasuis Taken together, these results demonstrate that PCV2 infection suppresses IL-12p40 expression to lower host Th1 immunity to increase the risk of other pathogenic infection via gC1qR-mediated PI3K/Akt1 and p38 MAPK signaling activation.

Establishment of method for dual simultaneous detection of PEDV and TGEV by combination of magnetic micro-particles and nanoparticles.

Transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PEDV) are the main pathogens causing viral diarrhea in pig, mixed infections of these two viruses are very common in intensive pig rearing. However, there is a lack of a method to simultaneously detect and distinguish PEDV and TGEV in preclinical levels. In this study, we aimed to establish a dual ultrasensitive nanoparticle DNA probe-based PCR assay (dual UNDP-PCR) based on functionalized magnetic bead enrichment and specific nano-technology amplification for simultaneous detection and distinguish diagnosis of PEDV and TGEV. The detection limit of dual UNDP-PCR for single or multiple infections of PEDV and TGEV is 25 copies/g, which is 400 times more sensitive than the currently known duplex RT-PCR, showing better specificity and sensitivity without cross-reaction with other viruses. For pre-clinical fecal samples, the dual UNDP-PCR showed a markedly higher positive detection rate (52.08%) than conventional duplex RT-PCR (13.21%), can rapidly and accurately identify targeted pathogens whenever simple virus infection or co-infection. In summary, this study provides a technique for detecting and distinguishing PEDV and TGEV in preclinical levels, which is high sensitivity, specificity, repeatability, low cost and broad application prospect.

Porcine MKRN1 Modulates the Replication and Pathogenesis of Porcine Circovirus Type 2 by Inducing Capsid Protein Ubiquitination and Degradation.

Porcine circovirus type 2 (PCV2) capsid protein (Cap) is a unique structure protein that plays pivotal roles in the process of viral replication and pathogenesis. Herein, we characterized a putative porcine Makorin RING finger protein 1 (pMKRN1) variant, an N-terminal-truncated variant of putative full-size porcine MKRN1 which has a unique expression pattern resulting from the porcine mkrn1 gene and which interacts with PCV2 Cap. A domain mapping assay showed that the C terminus of pMKRN1 and fragments (amino acids 108 to 198) of Cap are required for this interaction. PCV2 transiently upregulated pMKRN1 in PK-15 cells, but persistent viral infection downregulated pMKRN1 in major pathological tissues of PCV2-infected piglets. Overexpression of pMKRN1 significantly inhibited the generation of progeny PCV2 via ubiquitination and degradation of Cap, whereas knockout of pMKRN1 blocked Cap degradation and promoted progeny virus replication. pMKRN1 specifically targeted PCV2 Cap lysine residues 164, 179, and 191 to induce polyubiquitination and subsequent degradation. Mutation of either of the three lysine residues in the Cap protein or mutation of the histidine at residue 243 within the RING finger domain of pMKRN1 abrogated the E3 ligase activity of pMKRN1, rendering cells incapable of inducing Cap ubiquitination and degradation. Consistent with this finding, a Cap ubiquitination-deficient PCV2 strain showed enhanced virus replication and produced severe histological lesions in the lung and lymph node tissues compared with wild-type PCV2. Taken together, the results presented here suggest that PCV2 downregulates the pMKRN1 variant to avoid pMKRN1-mediated Cap ubiquitination and degradation, thus promoting viral replication and pathogenesis in its targeted tissues.IMPORTANCE Porcine circovirus type 2 is the pathogen to which pigs are the most susceptible, causing immense economic losses in the global swine industry, but whether host cells have developed some strategies to prevent viral replication is still unclear. Here, we found that porcine MKRN1 (pMKRN1) was upregulated in the early stage of PCV2 infection and mediated the polyubiquitination and degradation of Cap protein to block PCV2 replication, yet persistent PCV2 infection downregulated pMKRN1 levels to avoid degradation, promoting viral replication and pathogenesis in its targeted tissues. These data present new insight into the molecular mechanisms underlying the antiviral effects of pMKRN1 E3 ligase during PCV2 infection and also suggest potential new control measures for PCV2 outbreaks.

Identification and Expression Profiling of the Regulator of Chromosome Condensation 1 (RCC1) Gene Family in Gossypium Hirsutum L. under Abiotic Stress and Hormone Treatments.

The regulator of chromosome condensation 1 (RCC1) is the nucleotide exchange factor for a GTPase called the Ras-related nuclear protein, and it is important for nucleo-plasmic transport, mitosis, nuclear membrane assembly, and control of chromatin agglutination during the S phase of mitosis in animals. In plants, RCC1 molecules act mainly as regulating factors for a series of downstream genes during biological processes such as the ultraviolet-B radiation (UV-B) response and cold tolerance. In this study, 56 genes were identified in upland cotton by searching the associated reference genomes. The genes were found to be unevenly distributed on 26 chromosomes, except A06, A12, D03, and D12. Phylogenetic analysis by maximum-likelihood revealed that the genes were divided into five subgroups. The RCC1 genes within the same group shared similar exon/intron patterns and conserved motifs in their encoded proteins. Most genes of the RCC1 family are expressed differently under various hormone treatments and are negatively controlled by salt stress. Gh_A05G3028 and Gh_D10G2310, which encode two proteins located in the nucleus, were strongly induced under salt treatment, while mutants of their homoeologous gene (UVR8) in Arabidopsis and VIGS (virus induced gene silencing) lines of the two genes above in G. hirsutum exhibited a salt-sensitive phenotype indicating their potential role in salt resistance in cotton. These results provide valuable reference data for further study of RCC1 genes in cotton.

Electrochemical impedance investigation of Ni-free Co-Cr-Mo and Co-Cr-Mo-Ni dental casting alloy for partial removable dental prosthesis frameworks.

STATEMENT OF PROBLEM: The pH level of the oral environment influences corrosion in dental materials. Corrosion behaviors of Co-Cr-Mo and Co-Cr-Mo-Ni alloys in different pH environments remain undetermined. PURPOSE: The purpose of this in vitro study was to evaluate the surface properties and corrosion behaviors of Co-Cr-Mo and Co-Cr-Mo-Ni dental casting alloys in artificial saliva at pH values of 5.0 and 2.5. MATERIAL AND METHODS: Fifty specimens were divided into 2 groups according to the alloy composition. The surface compositions, hardness values, and microstructures of the alloys were measured before immersion in artificial saliva. The corrosion behaviors of the specimens in artificial saliva at pH values of 5.0 and 2.5 were studied using electrochemical impedance spectroscopy (EIS). The microstructures were examined again after a 7-day immersion test. Data were analyzed by a 1-way analysis of variance (ANOVA) test (α=.05). RESULTS: As expected, the relative levels of Co and Cr of the surface composition were higher in the Co-Cr-Mo alloy. The Co-Cr-Mo alloy had statistically higher surface hardness than the Co-Cr-Mo-Ni alloy (P<.05). In the pH 2.5 environment, both of the alloys showed decreased corrosion resistance (P<.05). The microstructure of the Co-Cr-Mo-Ni alloy corroded more than that of the Co-Cr-Mo alloy in the pH 2.5 environment. The oxide-layer corrosion resistance of the Co-Cr-Mo alloy was better than that of the Co-Cr-Mo-Ni alloy in Fusayama artificial saliva solutions at pH values of both 5.0 and 2.5 (P<.05). CONCLUSIONS: The corrosion resistance of the Co-Cr-Mo alloy was better in the oral environment, especially at a low pH value.

Early interim PET/CT predicts post-treatment response in diffuse large B-cell lymphoma.

BACKGROUND: (18)F-FDG-PET/CT has been widely used in the staging of malignant lymphomas, and accepted as a tool for response assessment. Among PET parameters, the most frequently studied is maximal standardized uptake value (SUVmax). Metabolic tumor burden (MTB) is a parameter in which both metabolic tumor volume (MTV) and tumor activity are integrated. Here, we analyzed the prognostic value of SUVmax, SUVsum (sum of the SUVmax), whole-body MTV (MTVwb) and MTBwb from baseline and interim PET/CT in patients with diffuse large B-cell lymphoma (DLBCL). MATERIAL AND METHODS: Twenty-nine patients with histologically proven DLBCL were imaged by PET/CT before treatment (Exam I), and one week after the first dose of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy (Exam II). Biopsy specimens were examined by an expert hematopathologist, the Ki-67 proliferation index (PI) was estimated for each biopsy site from the MIB-1 stained sections. The response evaluation was performed after chemotherapy completion (6-8 cycles). RESULTS: All patients had one or more visualized lymphomatous lesions on (18)F-FDG-PET/CT. The SUVmax of the whole-body (BmSUVmax) was higher than the SUVmax at biopsy site (BxSUVmax) (mean: 20.1 vs. 17.3, p < 0.01). The PI correlated with the BxSUVmax (p < 0.05). One week after chemotherapy, SUVmax, SUVsum, MTVwb, and MTBwb decreased significantly (p < 0.01, respectively), SUVsum, MTVwb and MTBwb at Exam II correlated with chemotherapy response at treatment completion (p < 0.05, respectively). CONCLUSION: SUVmax is more accurate to detect tumor aggressiveness than biopsy in DLBCL, since BmSUVmax represents the most aggressive tumor of the patient. Interim PET/CT as early as one week after R-CHOP therapy predicts response. Thus, it could be used as a tool for guidance of risk stratification in DLBCL.

The PCV3 Cap Virus-like Particle Vaccine with the Chimeric PCV2-Neutralizing Epitope Gene Is Effective in Mice.

Porcine circovirus type 3 (PCV3) infection can cause symptoms similar to those of porcine circovirus type 2 (PCV2) infection, and coinfections with both PCV2 and PCV3 are observed in the swine industry. Consequently, developing chimeric vaccines is essential to prevent and control porcine circovirus infections. In this study, we used both E. coli and mammalian expression systems to express PCV3 Cap (Cap3) and a chimeric gene containing the PCV2-neutralizing epitope within the PCV3 Cap (Cap3-Cap2E), which were assembled into virus-like particle (VLP) vaccines. We found that Cap3 lacking nuclear localization signal (NLS) could not form VLPs, while Cap3 with a His-tag successfully assembled into VLPs. Additionally, the chimeric of PCV2-neutralizing epitopes did not interfere with the assembly process of VLPs. Various immunization approaches revealed that pCap3-Cap2E VLP vaccines were capable of activating high PCV3 Cap-specific antibody levels and effectively neutralizing both PCV3 and PCV2. Furthermore, pCap3-Cap2E VLPs demonstrated a potent ability to activate cellular immunity, protecting against PCV3 infection and preventing lung damage in mice. In conclusion, this study successfully developed a PCV3 Cap VLP vaccine incorporating chimeric PCV2-neutralizing epitope genes, providing new perspectives for PCV3 vaccine development.

Comparison of different MRI sequences in lesion detection and early response evaluation of diffuse large B-cell lymphoma--a whole-body MRI and diffusion-weighted imaging study.

To compare different MRI sequences for the detection of lesions and the evaluation of response to chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL), 18 patients with histology-confirmed DLBCL underwent 3-T MRI scanning prior to and 1 week after chemotherapy. The MRI sequences included T1-weighted pre- and post-contrast, T2 -weighted with and without fat suppression, and a single-shot echo-planar diffusion-weighted imaging (DWI) with two b values (0 and 800 s/mm(2)). Conventional MRI sequence comparisons were performed using the contrast ratio between tumor and normal vertebral body instead of signal intensity. The apparent diffusion coefficient (ADC) of the tumor was measured directly on the parametric ADC map. The tumor volume was used as a reference for the evaluation of chemotherapy response. The mean tumor volume was 374 mL at baseline, and decreased by 65% 1 week after chemotherapy (p < 0.01). The T2 -weighted image with fat suppression showed a significantly higher contrast ratio compared with images from all other conventional MRI sequences, both before and after treatment (p < 0.01, respectively). The contrast ratio of the T2 -weighted image with fat suppression decreased significantly (p < 0.01), and that of the T1 -weighted pre-contrast image increased significantly (p < 0.01), after treatment. However, there was no correlation between the change in contrast ratio and tumor volume. The mean ADC value was 0.68 × 10(-3) mm(2)/s at baseline; it increased by 89% after chemotherapy (p < 0.001), and the change in ADC value correlated with the change in tumor volume (r = 0.66, p < 0.01). The baseline ADC value also correlated inversely with the percentage change in ADC after treatment (r = -0.62, p < 0.01). In conclusion, this study indicates that T2-weighted imaging with fat suppression is the best conventional sequence for the detection of lesions and evaluation of the efficacy of chemotherapy in DLBCL. DWI with ADC mapping is an imaging modality with both diagnostic and prognostic value that could complement conventional MRI.

Expanded functional coupling of subcortical nuclei with the motor resting-state network in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) impairs signal transmission along cortico-cortical and cortico-subcortical connections, affecting functional integration within the motor network. Functional magnetic resonance imaging (fMRI) during motor tasks has revealed altered functional connectivity in MS, but it is unclear how much motor disability contributed to these abnormal functional interaction patterns. OBJECTIVE: To avoid any influence of impaired task performance, we examined disease-related changes in functional motor connectivity in MS at rest. METHODS: A total of 42 patients with MS and 30 matched controls underwent a 20-minute resting-state fMRI session at 3 Tesla. Independent component analysis was applied to the fMRI data to identify disease-related changes in motor resting-state connectivity. RESULTS: Patients with MS showed a spatial expansion of motor resting-state connectivity in deep subcortical nuclei but not at the cortical level. The anterior and middle parts of the putamen, adjacent globus pallidus, anterior and posterior thalamus and the subthalamic region showed stronger functional connectivity with the motor network in the MS group compared with controls. CONCLUSION: MS is characterised by more widespread motor connectivity in the basal ganglia while cortical motor resting-state connectivity is preserved. The expansion of subcortical motor resting-state connectivity in MS indicates less efficient funnelling of neural processing in the executive motor cortico-basal ganglia-thalamo-cortical loops.

Ignition temperature and explosion pressure of suspended coal dust cloud under different conditions and suppression characteristics.

The ignition and explosion processes of suspended coal dust clouds and their suppression characteristics are important aspects of dust prevention and control. To understand the ignition temperature and explosion pressure of coal dust clouds, as well as the inhibitory effect of explosion suppressants, experimental tests are conducted. The study found that during the ignition process of coal dust clouds, the optimal dust spray pressure is 20 kPa, because coal dust clouds are more likely to ignite under this condition. When the mass concentration of coal dust cloud is 500 g m-3, the maximum pressure and maximum pressure rise rate are both the highest. When Al(OH)3 is mixed with coal dust and the mass percentage is 60%, the coal dust cloud can still be ignited. When KH2PO4 is mixed with coal dust, the upper limit of the test temperature is reached when the percentage of mixture is 55%. When NH4H2PO4 is mixed with coal dust and the mass percentage is greater than 40%, the coal dust cloud can't be ignited anymore. The suppression effect of mixing Al(OH)3 and NH4H2PO4 is not as good as that of mixing KH2PO4 and NH4H2PO4.

Volumetric MRI assessment of brain and spinal cord in Finnish twins discordant for multiple sclerosis.

BACKGROUND AND OBJECTIVE: Brain size, white matter hyperintensity, and the development of brain atrophy are known to be highly heritable. The decrease of brain volume starts from the very onset of multiple sclerosis and is 10-fold compared with normal aging. The aim of this study was to assess whether the brain and spinal cord volumes and the volume of white matter lesions differed between twins with multiple sclerosis and their asymptomatic co-twins. MATERIAL AND METHODS: A co-twin control method was used to evaluate whether the brain and spinal cord volumes differ between twins with multiple sclerosis and their co-twins. Nineteen twin pairs were studied neurologically, and the volumes of T1, T2, FLAIR, and gadolinium-enhanced lesions and those of the brain and the spinal cord were obtained by magnetic resonance imaging. RESULTS: Significant differences in the brain (P=0.064) or spinal cord (P=0.648) volumes were not detected. Four of the 7 monozygotic and 5 of the 12 dizygotic co-twins had focal brain white matter lesions, but none fulfilled the magnetic resonance imaging criteria of Barkhof. Spinal cord lesions were not seen in any of the co-twins. CONCLUSIONS: The absence of a significant difference in the brain or spinal cord volume between the twins with multiple sclerosis and their co-twins supports the recent observation of brain size and the development of brain atrophy being highly heritable.

Experimental Research on the Suppression Effect of Different Types of Inert Dust on Micron-Sized Lignite Dust Explosion Pressure in a Confined Space.

Coal is an important strategic resource in the world; coal production safety has always been widely concerned. In coal mine production, inert dust can effectively reduce coal dust explosion accidents in mine tunnels. To reveal the suppression effect of inert dust on lignite dust explosion, CaCO3, SiO2, and NH4H2PO4 are selected for suppression experiments. It is found that the lignite dust explosion pressure decreases continuously as the mass percentages of inert dust mixed into lignite dust increase. By calculating the molar mass, the suppression effects of CaCO3 and SiO2 on lignite dust explosion are compared. The lignite dust no longer explodes when the mass percentage of NH4H2PO4 dust mixed into lignite dust is 70%, indicating that NH4H2PO4 is more effective than that of CaCO3 and SiO2. The smaller the particle size of NH4H2PO4, the better the suppression effect on explosion. The lignite dust does not explode when the mass percentage of NH4H2PO4 is 60% and the particle size of NH4H2PO4 is 25-38 µm, which proves that decreasing the particle size of NH4H2PO4 is important to suppress explosion. The research results are of great significance for grasping the explosion suppression effect of inert dust on lignite dust.

Predictive mutation signature of immunotherapy benefits in NSCLC based on machine learning algorithms.

Background: Developing prediction tools for immunotherapy approaches is a clinically important and rapidly emerging field. The routinely used prediction biomarker is inaccurate and may not adequately utilize large amounts of medical data. Machine learning is a promising way to predict the benefit of immunotherapy from individual data by individuating the most important features from genomic data and clinical characteristics. Methods: Machine learning was applied to identify a list of candidate genes that may predict immunotherapy benefits using data from the published cohort of 853 patients with NSCLC. We used XGBoost to capture nonlinear relations among many mutation genes and ICI benefits. The value of the derived machine learning-based mutation signature (ML-signature) on immunotherapy efficacy was evaluated and compared with the tumor mutational burden (TMB) and other clinical characteristics. The predictive power of ML-signature was also evaluated in independent cohorts of patients with NSCLC treated with ICI. Results: We constructed the ML-signature based on 429 (training/validation = 8/2) patients who received immunotherapy and extracted 88 eligible predictive genes. Additionally, we conducted internal and external validation with the utility of the OAK+POPLAR dataset and independent cohorts, respectively. This ML-signature showed the enrichment in immune-related signaling pathways and compared to TMB, ML-signature was equipped with favorable predictive value and stratification. Conclusion: Previous studies proposed no predictive difference between original TMB and modified TMB, and original TMB contains some genes with no predictive value. To demonstrate that fewer genetic tests are sufficient to predict immunotherapy efficacy, we used machine learning to screen out gene panels, which are used to calculate TMB. Therefore, we obtained the 88-gene panel, which showed the favorable prediction performance and stratification effect compared to the original TMB.

RAP44 phage integrase-guided 50K genomic island integration in Riemerella anatipestifer.

Bacteriophages are viruses that infect bacteria. Bacteria and bacteriophages have been fighting for survival. Over time, the evolution of both populations has been affected. Pathogenic Flavobacteriaceae species including Riemerella anatipestifer mainly infects ducklings, geese, and turkeys. However, it does not infect humans, rats, or other mammals, and is a suitable and safe research object in the laboratory. Our previous study showed that there is a 10K genomic island in R. anatipestiferIn this study, we found another integrated 50K genomic islands and focused on the relationship between R. anatipestifer genomic islands and the RAP44 phage genome. The phage RAP44 genome was integrated into R. anatipestifer chromosome, and an evolutionary relationship was evident between them in our comparative analysis. Furthermore, the integrated defective RAP44 phage sequence had the function of integration, excision, and cyclization automatically. Integrases are important integration elements. The integrative function of integrase was verified in R. anatipestifer. The integrase with the attP site can be integrated stably at the attB locus of the R. anatipestifer genome. A recombinant strain can stably inherit and express the exogenous gene. By studying the integration between host bacterium and phage, we have provided evidence for the evolution of the genomes in R. anatipestifer.

Diffusion-weighted MRI in early chemotherapy response evaluation of patients with diffuse large B-cell lymphoma--a pilot study: comparison with 2-deoxy-2-fluoro- D-glucose-positron emission tomography/computed tomography.

To determine the feasibility of diffusion-weighted MRI (DWI) in the evaluation of the early chemotherapeutic response in patients with aggressive non-Hodgkin's lymphoma (NHL), eight patients with histologically proven diffuse large B-cell lymphoma were imaged by MRI, including DWI, and positron emission tomography/computed tomography (PET/CT) before treatment (E1), and after 1 week (E2) and two cycles (E3) of chemotherapy. In all patients, whole-body screening using T(1) - and T(2) -weighted images in the coronal plane was performed. To quantitatively evaluate the chemotherapeutic response, axial images including DWI were acquired. Apparent diffusion coefficient (ADC) maps were reconstructed, and the ADC value of the tumor was measured. In addition, the tumor volume was estimated on axial T(2) -weighted images. The maximum standardized uptake value (SUV(max) ) and active tumor volume were measured on fused PET/CT images. Lymphomas showed high signal intensity on DW images and low signal intensity on ADC maps, except for necrotic foci. The mean pre-therapy ADC was 0.71 × 10(-3) mm(2) /s; it increased by 77% at E2 (p < 0.05) and 24% more at E3 (insignificant); the total increase was 106% (p < 0.05). The mean tumor volume by MRI was 276 mL at baseline; it decreased by 58% at E2 (p < 0.05) and 65% more at E3 (p < 0.05), giving a total decrease of 84% (p < 0.05). All the imaged pre-therapy tumors were strongly positive on PET/CT, with a mean SUV(max) of 20. The SUV(max) decreased by 60% at E2 (p < 0.05) and 59% more at E3 (p < 0.05), giving a total decrease of 83% (p < 0.05). The active tumor burden decreased by 66% at E2 (p < 0.05). At baseline, both central and peripheral tumor ADC values correlated inversely with SUV(max) (p < 0.05), and also correlated inversely with active tumor burden on PET/CT and with tumor volume on MRI at E2 (p < 0.05). In conclusion, the results of DWI in combination with whole-body MRI were comparable with those of integrated PET/CT.

PET imaging in a longitudinal non-Hodgkin's lymphoma study: association with tumor volume.

BACKGROUND: Computed tomography (CT) is generally used in the evaluation of the treatment response of non-Hodgkin's lymphoma (NHL) patients. Instead of morphological images, positron emission tomography (PET) shows metabolic information that is connected to tumor activity, cell proliferation rate, and, thus, prognosis. PURPOSE: To determine the prognostic value of PET for tumor volume reduction measured by CT and magnetic resonance imaging (MRI) along with clinical characteristics in NHL patients. MATERIAL AND METHODS: We imaged 21 B-cell type NHL patients using whole-body 18F-FDG-PET at the onset and the completion of treatment and at six-month follow-up. The maximum standardized uptake value (SUV(max)) was calculated. Morphological tumor volume calculations were assessed using both MRI and CT. Additionally, patients underwent thorough clinical examination including several laboratory tests. RESULTS: A high SUV(max) was able to predict significant tumor volume reduction at the beginning of treatment, but the relation to pure tumor volume was poor. CONCLUSION: The SUV(max) values derived from FDG-PET seemed to correlate with volume changes but not with their absolute values or laboratory tests. Unlike MRI and CT, FDG-PET showed the disappearance of active tumors after treatment.