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Chronic pain is common in our population, and most of these patients are inadequately treated, making the development of safer analgesics a high priority. Knee osteoarthritis (OA) is a primary cause of chronic pain and disability worldwide, and lower extremity OA is a major contributor to loss of qualityadjusted life-years. In this study we tested the hypothesis that a novel JDNI8 replication-defective herpes simplex-1 viral vector (rdHSV) incorporating a modified carbonic anhydrase-8 transgene (CA8*) produces analgesia and treats monoiodoacetate-induced (MIA) chronic knee pain due to OA. We observed transduction of lumbar DRG sensory neurons with these viral constructs (vHCA8*) (~40% of advillin-positive cells and ~ 50% of TrkA-positive cells colocalized with V5-positive cells) using the intra-articular (IA) knee joint (KJ) route of administration. vHCA8* inhibited chronic mechanical OA knee pain induced by MIA was dose- and time-dependent. Mechanical thresholds returned to Baseline by D17 after IA KJ vHCA8* treatment, and exceeded Baseline (analgesia) through D65, whereas negative controls failed to reach Baseline responses. Weightbearing and automated voluntary wheel running were improved by vHCA8*, but not negative controls. Kv7 voltage-gated potassium channel-specific inhibitor XE-991 reversed vHCA8*-induced analgesia. Using IHC, IA KJ of vHCA8* activated DRG Kv7 channels via dephosphorylation, but negative controls failed to impact Kv7 channels. XE-991 stimulated Kv7.2-7.5 and Kv7.3 phosphorylation using western blotting of differentiated SH-SY5Y cells, which was inhibited by vHCA8* but not by negative controls. The observed prolonged dose-dependent therapeutic effects of IA KJ administration of vHCA8* on MIA-induced chronic KJ pain due to OA is consistent with the specific activation of Kv7 channels in small DRG sensory neurons. Together, these data demonstrate for the first-time local IA KJ administration of vHCA8* produces opioid-independent analgesia in this MIA-induced OA chronic pain model, supporting further therapeutic development. [ABSTRACT FROM AUTHOR]

To improve the low-load stable combustion capacity of a low-grade coal-fired boiler, this study proposed to reform C-layer secondary air, which was then used to improve the ignition and combustion stability of coal/airflow of a 600 MWe Foster Wheeler down-fired boiler. Cold airflow experiments and industrial measurements were carried out to investigate the influence of the new C-layer secondary air on the aerodynamic and combustion characteristics at low load under different C-layer secondary air ratios and damper openings, respectively. The flow and mixing characteristics of the C-layer secondary air and coal/airflow, the flue gas temperature and NOx, O2, and CO concentration distributions in the furnace at low load were examined. With increase in the C-layer secondary air ratio, the flow range of coal/airflow gradually expanded. The mixing distance first increased and then decreased. At an air ratio of 25%, the mixing distance was the longest. Industrial measurements showed that compared with that at the C-layer secondary air damper opening of 0%, the coal/airflow ignited earlier at 40% (corresponding to the C-layer secondary air ratio of 23.73%), and the flue gas temperature in the furnace increased substantially. At C-layer secondary air damper opening of 0%, 20%, and 40%, carbon content in the fly ash was 4.62%, 5.32%, and 4.20%, respectively. The respective NOx emissions at the furnace exits were 450 mg/Nm3, 378 mg/Nm3, and 427 mg/Nm3, (O2 = 6%). In actual operation, 40% is recommended as the optimal C-layer secondary air damper opening. [ABSTRACT FROM AUTHOR]

As a promising immune checkpoint of immunogenic cell death (ICD) and multifunctional calcium‐binding molecular chaperone, calreticulin (CALR) has been attracting increasing attention. CALR mainly locates in cellular endoplasmic reticulum and significantly affects cell proliferation, invasion, induction of apoptosis, and angiogenesis in breast invasive carcinoma (BRCA). CALR overexpression might be correlated with a worse outcome. Nonetheless, it remains obscure how CALR correlates with immune infiltration and survival prognosis of BRCA. In this study, we investigated CALR expression utilizing RNAseq data from the cancer genome atlas (TCGA) and genotype‐tissue expression (GTEx) database. The prognostic value of CALR was analyzed using clinical survival data. Enrichment analysis was conducted using the R package "clusterProfiler." We downloaded the immune cell infiltration score of TCGA samples from published articles and online databases and performed a correlation analysis between immune cell infiltration levels and CALR expression. We further assessed the association between CALR and immunomodulators. Moreover, we also evaluated the expression of CALR in 100 formalin‐fixed and paraffin‐embedded breast cancer and adjacent normal breast tissue specimens. Our results found that CALR was highly expressed in BRCA, and CALR expression levels differed in pathological stages, T stages, and N stages. Besides, these results suggested that CALR overexpression may have adverse effects on the progression‐free interval (PFI) and disease‐free interval (DFI), which may be related to tumor proliferation, invasion, and metastasis, leading to tumor deterioration. Meanwhile, immune cell infiltration analysis revealed a correlation between the expression of CALR and the number of neutrophils and dendritic cells, suggesting that CALR was highly correlated with many immunomodulators in BRCA. Our results provide potential biomarkers of CALR in BRCA. CALR may interact synergistically with other immunomodulators to regulate the immune microenvironment, which could be utilized to develop new immunotherapy drugs. [ABSTRACT FROM AUTHOR]

Mutations in superoxide dismutase 1 (SOD1) are responsible for 20% of familial ALS. Given the gain of toxic function in this dominantly inherited disease, lowering SOD1 mRNA and protein is predicted to provide therapeutic benefit. An early generation antisense oligonucleotide (ASO) targeting SOD1 was identified and tested in a phase I human clinical trial, based on modest protection in animal models of SOD1 ALS. Although the clinical trial provided encouraging safety data, the drug was not advanced because there was progress in designing other, more potent ASOs for CNS application. We have developed next- generation SOD1 ASOs that more potently reduce SOD1 mRNA and protein and extend survival by more than 50 days in [SOD1.sup.G93A] rats and by almost 40 days in [SOD1.sup.G93A] mice. We demonstrated that the initial loss of compound muscle action potential in [SOD1.sup.G93A] mice is reversed after a single dose of SOD1 ASO. Furthermore, increases in serum phospho-neurofilament heavy chain levels, a promising biomarker for ALS, are stopped by SOD1 ASO therapy. These results define a highly potent, new SOD1 ASO ready for human clinical trial and suggest that at least some components of muscle response can be reversed by therapy., Introduction Amyotrophic lateral sclerosis (ALS) is caused by the loss and dysfunction of neurons in motor pathways and leads to severe weakness, stiffness, and ultimately death in 3-5 years. Approximately [...]

To address the problem of late ignition and poor burnout of Foster-Wheeler down-fired boilers, this study proposed a new combustion technology, which combines adding on arch secondary air and alternately arranging the fuel-lean coal/airflow (FLCA) and fuel-rich coal/airflow (FRCA). The coal particle trajectories of FLCA and FRCA and overall aerodynamic characteristics in the furnace were studied at FRCA and FLCA ratio (RRL) of 5:5, 7:3, and 9:1. The results showed that even at a low FRCA ratio, the new combustion technology could still effectively ensure the penetration depth of pulverised coal/airflow. At different RRL values, the main airflow from the arch appeared in the near-wall area and could penetrate downwards into the cold ash hopper area. With an increase in the value of RRL, the deflection degree of FLCA towards the furnace wall increased, while that of FRCA decreased. At RRL of 7:3, both the penetration depth and deflection degree of FRCA and FLCA were at a high level, which was conductive to promoting the burnout and recommended in practical applications. [ABSTRACT FROM AUTHOR]

To effectively control the flow and combustion of pulverised coal in down-fired boilers and improve their thermal efficiency while ensuring low NOx emissions, on arch secondary air (OASA) combustion technology and a smoke-tracing analysis were proposed. The aerodynamic characteristics of a 300-MWe Foster Wheeler (FW) down-fired boiler with the OASA ratios (ROASA) of 0%, 10%, 20%, and 30%, the flow trajectories and mixing characteristics of OASA, and fuel-rich coal/air flow (FRA) and fuel-lean coal/air flow (FLA) were studied experimentally. For the ROASA of <10%, FRA and FLA flow to furnace centre soon after they are injected into the furnace. OASA and FLA may mix with FRA before ignition. For the ROASA of 20% or higher, FRA and FLA flow to the near-wall area soon after being injected into the furnace. FRA mixes with OASA after ignition. With the increase in ROASA, the mixing distance between OASA and FRA increases first and then decreases. The penetration depth of coal/air flow and furnace airflow fullness increases. For the ROASA of 30%, the dimensionless penetration depth of coal/air flow can exceed 0.7. Furnace dimensionless airflow fullness at all the dimensionless heights can exceed 0.6. In real operation, the recommended ROASA is between 20 and 30%. [ABSTRACT FROM AUTHOR]

Gallbladder cancer (GBC) ranks seventh among the gastrointestinal cancers. Messenger RNAs (mRNAs) could regulate the progression of GBC. For the purpose of exploring the targets for GBC treatment, RNA sequencing was used to identify the differential expressed mRNAs between GBC and adjacent tissues. Next, CCK8 assay was used to assess the cell viability, and cell proliferation was investigated by colony formation assay. Flow cytometry was performed to evaluate the cell apoptosis. Protein and mRNA expression were analyzed by western blot and RT‐qPCR, respectively. Transwell was performed to evaluate the cell metastasis. GBC‐derived exosomes were isolated with ultracentrifugation. To evaluate the function of exosomes in GBC, in vivo model of GBC was constructed. The data revealed IGF2BP3 was identified to be upregulated in GBC, and IGF2BP3 silencing was able to decrease GBC cell proliferation by promoting the apoptosis. The migration and invasion of GBC cells were reduced by IGF2BP3 knockdown. Silencing of IGF2BP3 obviously suppressed the level of p‐STAT3 in GBC cells. Meanwhile, GBC cell‐derived exosomes notably promoted macrophage M2 polarization via carrying IGF2BP3, and then the polarized macrophages promoted the malignant behavior of GBC cells. Furthermore, exosomes markedly promoted the tumor growth of GBC via promoting macrophage M2 polarization. In summary, knockdown of IGF2BP3 suppressed the malignant behavior of GBC cells. Additionally, knockdown of IGF2BP3 modified tumor microenvironment during the progression of GBC. Thus, these findings might provide a new theoretical basis for exploring a strategies against GBC. [ABSTRACT FROM AUTHOR]

To further reduce the NOx emissions of the down‐fired boiler while improving its low‐load stable combustion capacity, a new low NOx combustion organization mode that utilizes the high velocity parallel oil‐secondary air to improve the pulverized coal combustion process was proposed based on a novel stable combustion technology. We carried out cold airflow experiments under different oil‐secondary air and F‐layer secondary air distributions (mass flow rate ratios of 1:9, 1:3, 2:3) based on a 300 MWe Foster Wheeler down‐fired boiler to study its influence on the flow and mixing characteristics of the coal/airflow. Results show that the mixing between the oil‐secondary air and the fuel‐rich coal/airflow is gradually delayed with the increase of the secondary air distribution. When the secondary air distribution reaches more than 2:3, the oil‐secondary air starts to become the dominant airflow that influences the whole flow field in the furnace. Based on the result of the cold airflow experiment, we carried out industrial measurements under different parallel oil‐secondary air and F‐layer secondary air distributions (4:6, 5:5, 6:4) on a 600 MWe FW down‐fired boiler under the condition of using the high velocity oil‐secondary air. The ignition distance of the fuel‐rich coal/airflow, the flue gas temperature, the O2, CO, and NOx concentrations in the furnace were measured. At the secondary air distribution of 4:6, the ignition distance of the fuel‐rich coal/airflow was about 1.31 m. When the secondary air distribution was increased to 5:5 and 6:4, the ignition was put off, but the pulverized coal/airflow could still catch on fire in time. With the increase of the parallel oil‐secondary air proportion, the flame center in the furnace did not move downward substantially. In three cases, the lowest O2 concentrations in the inspection port area under the burner were all below 1% (peak CO concentration values were all above 28,000 ppm). The pulverized coal all burned in a strong reducing atmosphere. At secondary air distributions of 4:6, 5:5, and 6:4, NOx emissions of the boiler were, respectively, 825.83, 819.48, and 853.86 mg/Nm3 (O2 = 6%). The thermal efficiency was, respectively, 90.09%, 89.16%, and 90.98%. In actual operation, the recommended secondary air distribution is 6:4. [ABSTRACT FROM AUTHOR]

Evening primrose oil has a high market value due to its rich unsaturated fatty acids, so it is likely to be adulterated under the drive of economic interests. In this study, evening primrose oil's fatty acid and physicochemical properties are systematically determined, and the characteristic fatty acids are screened out. The feasibilities of GC‐MS and FT‐IR in identifying oil adulteration are also evaluated. Evening primrose oil's major fatty acids are linoleic acid (C18:2), γ‐linolenic acid (C18:3n6), palmitic acid (C16:0), oleic acid (C18:1), and stearic acid (C18:0). In addition, palmitoleic acid (C16:1), hexadecadienoic acid (C16:2), nonadecanoic acid (C19:0), eicosatrienoic acid (C20:3), erucic acid (C22:1), tricosanoic acid (C23:0) and lignoceric acid (C24:0) are rarely detected in other related studies on the evening primrose oil. This study uses fatty acids as indicators, hierarchical cluster analysis, and cosine similarity analysis to identify the evening primrose oil mixed with >5% peanut oil and >10% sunflower oil. Besides, the principal component analysis also distinguishes evening primrose oil blended with different proportions of peanut and sunflower oils. In summary, this study confirms that fatty acids can be characteristic indexes to identify adulterated evening primrose oil by GC‐MS and FT‐IR combined with chemometrics. Practical Applications: This study further clarifies the major and characteristic fatty acids of evening primrose oil. On this basis, the adulteration of evening primrose oil (taking peanut oil and sunflower oil as an example) is identified. Therefore, it is helpful to assess the quality and identify the authenticity of the evening primrose oil, which is vital for the stability of the evening primrose oil market and the interests of consumers. These methods combined with chemometrics can also be extended to ensure the certification of other oils and to classify oils into different classes. The improvements in vegetable oil quality will also benefit the vegetable oil industry and control bodies. [ABSTRACT FROM AUTHOR]

Background. Inflammatory breast cancer (IBC) is one of the most rare and aggressive subtypes of primary breast cancer (BC). Our study aimed to explore hub genes related to the pathogenesis of IBC, which could be considered as novel molecular biomarkers for IBC diagnosis and prognosis. Material and Methods. Two datasets from gene expression omnibus database (GEO) were selected. Enrichment analysis and protein-protein interaction (PPI) network for the DEGs were performed. We analyzed the prognostic values of hub genes in the Kaplan-Meier Plotter. Connectivity Map (CMap) and Comparative Toxicogenomics Database (CTD) was used to find candidate small molecules capable to reverse the gene status of IBC. Results. 157 DEGs were selected in total. We constructed the PPI network with 154 nodes interconnected by 128 interactions. The KEGG pathway analysis indicated that the DEGs were enriched in apoptosis, pathways in cancer and insulin signaling pathway. PTEN, PSMF1, PSMC6, AURKB, FZR1, CASP9, CASP6, CASP8, BAD, AKR7A2, ZNF24, SSX2IP, SIGLEC1, MS4A4A, and VSIG4 were selected as hub genes based on the high degree of connectivity. Six hub genes (PSMC6, AURKB, CASP9, BAD, ZNF24, and SSX2IP) that were significantly associated with the prognosis of breast cancer. The expression of CASP9 protein was associated with prognosis and immune cells infiltration of breast cancer. CASP9- naringenin (NGE) is expected to be the most promising candidate gene-compound interaction for the treatment of IBC. Conclusion. Taken together, CASP9 can be used as a prognostic biomarker and a novel therapeutic target in IBC. [ABSTRACT FROM AUTHOR]

The dynamic of soil-borne disease is closely related to the rhizosphere microbial communities. Maize–soybean relay strip intercropping has been shown to significantly control the type of soybean root rot that tends to occur in monoculture. However, it is still unknown whether the rhizosphere microbial community participates in the regulation of intercropped soybean root rot. In this study, rhizosphere Fusarium and Trichoderma communities were compared in either healthy or root-rotted rhizosphere soil from monocultured and intercropped soybean, and our results showed the abundance of rhizosphere Fusarium in intercropping was remarkably different from monoculture. Of four species identified, F. oxysporum was the most aggressive and more frequently isolated in diseased soil of monoculture. In contrast, Trichoderma was largely accumulated in healthy rhizosphere soil of intercropping rather than monoculture. T. harzianum dramatically increased in the rhizosphere of intercropping, while T. virens and T. afroharzianum also exhibited distinct isolation frequency. For the antagonism test in vitro, Trichoderma strains had antagonistic effects on F. oxysporum with the percentage of mycelial inhibition ranging from 50.59–92.94%, and they displayed good mycoparasitic abilities against F. oxysporum through coiling around and entering into the hyphae, expanding along the cell–cell lumen and even dissolving cell walls of the target fungus. These results indicate maize–soybean relay strip intercropping significantly increases the density and composition proportion of beneficial Trichoderma to antagonize the pathogenic Fusarium species in rhizosphere, thus potentially contributing to the suppression of soybean root rot under the intercropping. [ABSTRACT FROM AUTHOR]

Sea salts act as an important medium for atmospheric processing. One intensive field campaign in the September–October period of 2019 was conducted at a subtropical coastal site over the South China Sea. Unexpected high concentrations of acidic gaseous precursors were observed, yielding high sulfate in PM2.5. Na+ ranked as the third highest inorganic species, about half of NH4+. Significant cation deficiency was found due to the ammonia‐poor environment. Diel patterns of most air pollutants from land breeze were stronger than that from marine breeze and presented pronounced unimodal distributions, which were ascribed to complex chemical processing mixed with regional transport. Thermodynamic equilibrium model (ISORROPIA II) simulation revealed sea salts could be internally mixed with fine particle secondary species and suggested evident multiphase reactions on sea salts. The simulated aerosol pH reached as low as 1.63 ± 0.50, which was related to high sulfate, insufficient alkaline species, and low aerosol liquid water content. During a continuous sea breeze episode, SO42− was underpredicted by 2.89 ± 3.85 μg m−3 if Na+ was not considered in ISORROPIA simulation. The retrieved Na+ ‐related ion pairs (NaCl, NaHSO4, and Na2SO4) accounted for about one‐fourth of the total inorganic aerosols. This study highlighted that intense atmospheric processing on sea salts occurred in fine particles and the mixing state between sea salts and other aerosol species should be considered in aerosol acidity prediction and secondary aerosol formation in coastal regions. Key Points: Sea salts were internally mixed with the secondary species even in fine particle, suggesting evident multiphase reactions on sea saltsAerosol pH was very low at the land‐sea interface and it depended on the relative strengths of sea salts versus terrestrial ammonia emissionsThe retrieved chemical forms of SO42− contained a substantial contribution from bisulfate, mainly in the form of NaHSO4 and NH4HSO4 [ABSTRACT FROM AUTHOR]

Kagome lattice defect modes with a point-ring structure are explored theoretically in two-dimensional germanium cylinder photonic crystals using plane wave expansion and supercell methods. The number and degeneracy of the transverse magnetic field defect mode are governed by the defect setting. By varying the distance and direction of the point-ring defects, we can manipulate and control the frequency width and coupling between defect modes and the defect frequency in the bandgap. Additionally, the intensity distribution localized in the defect position is related to the parity of defect structure symmetry axes. This characteristic is highly beneficial to applications such as in resonators and narrow band filters. [ABSTRACT FROM AUTHOR]