Conventional Type Research Articles

Photoproduction of Loop Currents in Coronene Isomers Without Any Applied Magnetic Field

Applying an extended Peierls–Hubbard model to π electrons in a coronene isomer, we investigate their ground-state properties and photoinduced dynamics with particular interest in possible loop current states. Once we switch on a static magnetic field perpendicular to the coronene disk, diamagnetic (diatropic) and paramagnetic (paratropic) loop currents appear on the rim circuit and inner hub, respectively. Besides this well-known homocentric two-loop current state, heterocentric multiloop current states can be stabilized by virtue of possible electron–lattice coupling. These multiloop current states generally have a larger diamagnetic moment than the conventional two-loop one, and hence it follows that coronene, or possibly polycyclic conjugated hydrocarbons in general, may become more aromatic than otherwise with their π electrons being coupled to phonons. When we photoirradiate a ground-state coronene isomer without applying a static magnetic field, loop currents are induced in keeping with the incident light polarization. Linearly and circularly polarized lights induce heterocentric two-loop and multiloop currents, respectively, without and together with two homocentric loop currents of the conventional type, respectively. The heterocentric two-loop currents occur in a mirror-symmetric manner, which reads as the emergence of a pair of antiparallel magnetic moments, whereas the heterocentric multiloop ones appear at random in both space and time, which reads as the emergence of disordered local magnetic moments.

Alteration of the Tumor Microenvironment With Intratumoral Dendritic Cells Before Chemotherapy in ERBB2 Breast Cancer

Current chemotherapy regimens for patients with ERBB2 (formerly HER2)-positive breast cancer are associated with considerable morbidity. These patients may benefit from more effective and less toxic therapies. To evaluate the safety, immunogenicity, and preliminary efficacy of intratumoral (IT) delivery of conventional type 1 dendritic cells (cDC1) in combination with ERBB2-targeted therapies. This phase 1 (lead-in phase of a single-center phase 2 trial) nonrandomized clinical trial was conducted at Moffitt Cancer Center (Tampa, Florida). Patients were enrolled from October 2021 to October 2022. Data were analyzed in 2023 Patients with early-stage ERBB2-positive breast cancer with tumors 1 cm or larger were eligible. Treatment included IT delivery of cDC1, 6 times weekly, followed by paclitaxel, 80 mg/m2, intravenously, 12 times weekly. Trastuzumab (8 mg/kg loading dose, then 6 mg/kg) and pertuzumab (840 mg loading dose, then 420 mg) were administered intravenously every 3 weeks for 6 cycles starting from day 1 of cDC1 injections. Two dose levels (DLs) of IT cDC1 (DL1 = 50 million and DL2 = 100 million cells) were evaluated, including 6 patients in each DL. The primary outcomes were the safety and immune response, and the secondary outcomes were the antitumor efficacy as measured by breast magnetic resonance imaging and residual cancer burden at surgery following neoadjuvant therapy. Twelve ERBB2-positive patients were enrolled and received treatment (DL1 = 6 and DL2 = 6). Nine patients had hormone receptor-positive disease and 3 had hormone receptor-negative disease, with clinical stage I (n = 5), II (n = 4), and III (n = 3). The most frequently observed adverse events with cDC1 were grade 1 to 2 chills (50%), fatigue (41.7%), headache (33%), and injection site reactions (33%). DL2 was associated with a diminished anti-ERBB2 CD4 T-helper 1 blood response with a concomitant increase in innate and adaptive responses within the tumor. Preimmunotherapy and postimmunotherapy breast magnetic resonance imaging results showed 9 objective responses, 6 partial responses, 3 complete responses, and 3 stable diseases. Following surgery, 7 patients had a pathologic complete response. In this nonrandomized clinical trial, the addition of IT cDC1 and trastuzumab/pertuzumab before neoadjuvant chemotherapy was well tolerated with manageable adverse effects. Based on safety and immunogenicity, DL2 was selected for the phase 2 dose. ClinicalTrials.gov Identifier: NCT05325632.

A fish-friendly axial flow pump turns out to be eel safe, roach unfriendly and bream unsafe

Additional and refurbished pumping stations are required to mitigate the intensifying occurrence of droughts and floodings. These installations negatively impact threatened freshwater fish populations due to the increased risk of injury and mortality when fish pass through them. Fish-friendly pumping installations have been proposed as a potential solution to reduce these risks. However, published assessments of these new types of pumps remains lacking, and the few available studies do not enable a cross-comparison with conventional pump types. The promising, yet understudied, Fairbank Nijhuis ‘fish-friendly’ axial flow pump has been assessed in previous works, however the results remain ambiguous due to low recapture rates, unconsidered parameters, fixed operating conditions, and the inability to identify the likely sources of injury and mortality. In this study, we address the limitations of previous works by implementing a standardized protocol for live fish in conjunction with passive barotrauma detection sensors. The major finding of this work is that safe passage of eel (100% survival) is confirmed, but that bream and roach had a much lower survival probability (24% and 70% survival respectively) than expected, albeit higher than for a conventional axial flow pump (roach survival: 13%). Furthermore, roach and bream passing at higher rpm suffered significantly higher mortalities. The impact of the impeller was found to be the most common source of severe injury for both pumps. These results are significant because they conclusively show that fish-friendly pumps may be considered safe for eel, but not for other endemic European fish species such as roach and bream.

Research on supercritical CO2-based filled type U-pipe solar evacuated tubular collector: A thermodynamically parametric optimization and implementation machine learning modeling

Using supercritical CO2 as a working fluid in a heat and power system operating on solar energy is an advantageous approach that achieves higher efficiency, carbon capture, and emissions reduction. Therefore, the present work focused on researching the effectiveness of developing a supercritical CO2-based U-pipe solar evacuated tubular collector (ETC) by a filled layer that includes contributions to thermodynamic parametric optimization and machine learning modeling to forecast the outlet temperature intelligently. Results indicated that the filled type increase the outlet temperature by 24.29 % compared with the conventional type. The evaluation of the optimization research findings shows that an optimal mass flow rate of 8.0 kg/hr achieves a maximum exergy efficiency of 13.70 % to 14.51 %. Furthermore, the results recommended that arranging 13 tubes with a length of 1800 mm is optimal for exergy efficiency within a mass flow rate range of 6.0–12.0 kg/hr. Based on machine learning implementations, Gradient Boosting, Support Vector Machine, and Multi-Layer Perceptron neural networks can intelligently predict with R2|Tout = 1.000, 0.997, and 0.995, respectively. A polynomial-based GMDH/ML with R2|Tout = 0.986 was presented to intelligently forecast the outlet temperature using five input (Tamb,ṁ,ηopt,Ltube,It) parameters.

Altered Immune Cell Profiles in the Follicular Fluid of Patients with Poor Ovarian Response According to the POSEIDON Criteria

Altered Immune Cell Profiles in the Follicular Fluid of Patients with Poor Ovarian Response According to the POSEIDON Criteria

Ribosome profiling shows variable sensitivity to detect open reading frames for conventional and different types of cryptic T-cell antigens.

Ribosome profiling shows variable sensitivity to detect open reading frames for conventional and different types of cryptic T-cell antigens.

Complex phase behaviours related to gas injection in reservoir fluids

Enhanced oil recovery (EOR) involves several techniques, including the injection of gas (such as natural gas, nitrogen, or CO2) into the reservoir to increase its pressure, thereby displacing oil from one or more injection wells to production wells. For this process to be effective, it is essential that the injected gas and the oil reach a homogeneous state. Particularly, the First-Contact Minimum Miscibility Pressure (FC-MMP) offers a reliable (and safe) initial estimate for the pressure at which the EOR process should be conducted. In this work, an efficient algorithm is developed that allows computing complete pressure(P)-α diagrams (α: percentage of injected gas) at a fixed temperature using traditional cubic equations of state (EoS), including complex cases with three-phase regions. This algorithm is used to study both the qualitative and quantitative behaviour of the P-α diagrams and to analyse how FC-MMP changes with the injection of different gases or gas mixtures. Various reservoir fluids from the literature (with and without asphaltenes and with varying levels of CO2 and methane) are evaluated. In one section, three injection gases are used: CO2, N2, and a synthetic natural gas mixture, comparing their effects on the P-α diagrams. Then, the impact of interaction parameters on phase equilibrium and FC-MMP is analysed, and the role of asphaltene precipitation is discussed. The study concludes with a quantitative comparison between the FC-MMP calculated here and the Multiple-Contact MMP (MC-MMP) reported for the same fluids. Additionally, the problem of whether asphaltenes precipitation should be considered or ignored in the determination of the FC-MMP is analysed and discussed, with different perspectives for conventional and non-conventional shale type reservoirs.

Introducing Degradable Cationic Nanogels Carrying TLR9 Stimulating Oligonucleotides.

Cationic, core-crosslinked nanogel particles are prepared from synthetic biodegradable materials. These fully hydrophilic nanogels offer superior customizability compared to common lipid nanoparticles, thereby circumventing intrinsic immune stimulatory properties. Electrostatic loading allows for complexation of nucleic acids including the immune stimulatory Toll-like receptor 9 (TLR9) agonistCpG-ODN (cytidine-phosphate-guanosine oligodeoxynucleotide). Only when complexed inside nanogels, one can control CpG-ODN's biodistribution, prevent systemic toxicity, and increase bioavailability at target locations. Nanogels are prepared from cyclic aliphatic carbonate monomers with reactive pentafluorophenyl (PFP) esters. First, block copolymers are acquired via cationic ring opening polymerization (CROP) onto polyethylene glycol (PEG). Upon self-assembly in ethanol, the micelles' core is cationically core-crosslinked, and the resulting fully hydrophilic particles exhibit sizes of ≈20nm, also upon loading with CpG-ODN. In vitro, they promote intracellular delivery devoid of carrier-related toxicities, while retaining the immune stimulatory properties of the TLR agonist cargo. In vivo, the nanogels reduce systemic liver immune responses and remain near the injection site. Additionally, delivery into cDC1 (conventional dentritic cells type 1) antigen-presenting cells, which are highly relevant for antitumoral T-cell immune responses, is confirmed. Altogether, cationic, core-crosslinked polycarbonate nanogels show promise for nucleic acid delivery, showcasing controlled immunostimulatory cargo delivery and an enhanced hydrolytic biodegradability profile, highly valuable for cancer immunotherapy.

Targeting CD206+ macrophages disrupts the establishment of a key antitumor immune axis.

CD206 is a common marker of a putative immunosuppressive "M2" state in tumor-associated macrophages (TAMs). We made a novel conditional CD206 (Mrc1) knock-in mouse to specifically visualize and/or deplete CD206+ TAMs. Early depletion of CD206+ macrophages and monocytes (Mono/Macs) led to the indirect loss of conventional type I dendritic cells (cDC1), CD8 T cells, and NK cells in tumors. CD206+ TAMs robustly expressed CXCL9, contrasting with stress-responsive Spp1-expressing TAMs and immature monocytes, which became prominent with early depletion. CD206+ TAMs differentially attracted activated CD8 T cells, and the NK and CD8 T cells in CD206-depleted tumors were deficient in Cxcr3 and cDC1-supportive Xcl1 and Flt3l expressions. Disrupting this key antitumor axis decreased tumor control by antigen-specific T cells in mice. In human cancers, a CD206Replete, but not a CD206Depleted Mono/Mac gene signature correlated robustly with CD8 T cell, cDC1, and NK signatures and was associated with better survival. These findings negate the unqualified classification of CD206+ "M2-like" macrophages as immunosuppressive.

Physical and Mechanical Properties of Bulk-fill Resin Composites Submitted to Additional Polymerization for Use in Semi-direct Restorations.

Physical and mechanical properties of high-viscosity bulk-fill resin composites submitted to additional polymerization for semi-direct use were evaluated. Filtek Z350 XT, Aura Bulk Fill, Beautifil Bulk Restorative, Filtek One Bulk Fill Restorative, and Tetric N-Ceram Bulk Fill were submitted to additional polymerization to evaluate sorption, solubility, surface microhardness, surface roughness before and after simulated brushing, color stability after coffee staining, flexural strength, elastic modulus, and modulus of resilience. Filtek Z350 XT and Filtek One Bulk Fill Restorative showed higher sorption values, while Aura Bulk Fill showed higher solubility (p<0.0001). Microhardness values were significantly higher for Filtek Z350 XT (p<0.0001). Roughness increased after wear for all resins (p<0.05). All resins exhibited staining, with significantly higher ΔEab, ΔE00, and ΔWID values observed for Beautifil Bulk Restorative (p<0.0001). Flexural strength values were higher for Filtek Z350 XT and Filtek One Bulk Fill Restorative in comparison with the others (p<0.0001). Filtek One Bulk-Fill had higher elastic modulus and modulus of resilience values (p<0.0001). Physical and mechanical properties varied according to the composition. None of the bulk-fill resins showed surface microhardness and roughness properties after brushing similar to or superior to those of the conventional type. Color stability after staining depended on resin composition, with Beautifil Bulk Restorative showing more intense staining.

5.5 GHz film bulk acoustic wave filters using thin film transfer process for WLAN applications

Wireless local area network (WLAN) has gained widespread application as a convenient network access method, demanding higher network efficiency, stability, and responsiveness. High-performance filters are crucial components to meet these needs. Film bulk acoustic resonators (FBARs) are ideal for constructing these filters due to their high-quality factor (Q) and low loss. In conventional air-gap type FBAR, aluminum nitride (AlN) is deposited on the sacrificial layer with poor crystallinity. Additionally, FBARs with single-crystal AlN have high internal stress and complicated fabrication process. These limit the development of FBARs to higher frequencies above 5 GHz. This paper presents the design and fabrication of FBARs and filters for WLAN applications, combining the high electromechanical coupling coefficient (Kt2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${K}_{{\\rm{t}}}^{2}$$\\end{document}) of Al0.8Sc0.2N film with the advantages of the thin film transfer process. An AlN seed layer and 280 nm-thick Al0.8Sc0.2N are deposited on a Si substrate via physical vapor deposition (PVD), achieving a full width at half maximum (FWHM) of 2.1°. The ultra-thin film is then transferred to another Si substrate by wafer bonding, flipping, and Si removal. Integrating conventional manufacturing processes, an FBAR with a resonant frequency reaching 5.5 GHz is fabricated, demonstrating a large effective electromechanical coupling coefficient (keff2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${{k}}_{{\\rm{eff}}}^{2}$$\\end{document}) of 13.8% and an excellent figure of merit (FOM) of 85. A lattice-type filter based on these FBARs is then developed for the Wi-Fi UNII-2 band, featuring a center frequency of 5.5 GHz and a −3 dB bandwidth of 306 MHz, supporting high data rates and large throughputs in WLAN applications.

Genomic surveillance of multidrug-resistant organisms based on long-read sequencing

BackgroundMultidrug-resistant organisms (MDRO) pose a significant threat to public health worldwide. The ability to identify antimicrobial resistance determinants, to assess changes in molecular types, and to detect transmission are essential for surveillance and infection prevention of MDRO. Molecular characterization based on long-read sequencing has emerged as a promising alternative to short-read sequencing. The aim of this study was to characterize MDRO for surveillance and transmission studies based on long-read sequencing only.MethodsGenomic DNA of 356 MDRO was automatically extracted using the Maxwell-RSC48. The MDRO included 106 Klebsiella pneumoniae isolates, 85 Escherichia coli, 15 Enterobacter cloacae complex, 10 Citrobacter freundii, 34 Pseudomonas aeruginosa, 16 Acinetobacter baumannii, and 69 methicillin-resistant Staphylococcus aureus (MRSA), of which 24 were from an outbreak. MDRO were sequenced using both short-read (Illumina NextSeq 550) and long-read (Nanopore Rapid Barcoding Kit-24-V14, R10.4.1) whole-genome sequencing (WGS). Basecalling was performed for two distinct models using Dorado-0.3.2 duplex mode. Long-read data was assembled using Flye, Canu, Miniasm, Unicycler, Necat, Raven, and Redbean assemblers. Long-read WGS data with > 40 × coverage was used for multi-locus sequence typing (MLST), whole-genome MLST (wgMLST), whole-genome single-nucleotide polymorphisms (wgSNP), in silico multiple locus variable-number of tandem repeat analysis (iMLVA) for MRSA, and identification of resistance genes (ABRicate).ResultsComparison of wgMLST profiles based on long-read and short-read WGS data revealed > 95% of wgMLST profiles within the species-specific cluster cut-off, except for P. aeruginosa. The wgMLST profiles obtained by long-read and short-read WGS differed only one to nine wgMLST alleles or SNPs for K. pneumoniae, E. coli, E. cloacae complex, C. freundii, A. baumannii complex, and MRSA. For P. aeruginosa, differences were up to 27 wgMLST alleles between long-read and short-read wgMLST and 0–10 SNPs. MLST sequence types and iMLVA types were concordant between long-read and short-read WGS data and conventional MLVA typing. Antimicrobial resistance genes were detected in long-read sequencing data with high sensitivity/specificity (92–100%/99–100%). Long-read sequencing enabled analysis of an MRSA outbreak.ConclusionsWe demonstrate that molecular characterization of automatically extracted DNA followed by long-read sequencing is as accurate compared to short-read sequencing and suitable for typing and outbreak analysis as part of genomic surveillance of MDRO. However, the analysis of P. aeruginosa requires further improvement which may be obtained by other basecalling algorithms. The low implementation costs and rapid library preparation for long-read sequencing of MDRO extends its applicability to resource-constrained settings and low-income countries worldwide.

Abstract B028: The Role of cDC1 Gene Signatures in gastric cancer prognosis and immune microenvironment modulation

Abstract Background and Aim: Gastric cancer (GC) continues to be a major global health burden, with a growing body of evidence highlighting the critical role of conventional type 1 dendritic cells (cDC1s) within the tumor microenvironment. This study aims to elucidate the prognostic significance of cDC1-associated genes—CD141, XCR1, CLEC9A, CADM1, and BTLA—in gastric cancer, as well as to explore the biological mechanisms that underpin their effects on patient outcomes. Materials and Methods: We conducted a comprehensive analysis of RNA- seq data from The Cancer Genome Atlas (TCGA-STAD) and Gene Expression Omnibus (GEO) datasets, focusing on the expression profiles of five cDC1-related genes. Patients were stratified into high and low expression groups based on a defined cDC1 gene signature. To assess the impact of these signatures, we utilized gene set variation analysis (GSVA) to examine relevant oncogenic pathways and performed Kaplan-Meier survival analysis along with Cox proportional hazards modeling to evaluate their prognostic value. Results: Our findings demonstrate that patients exhibiting a high cDC1-related gene signature had significantly worse overall and disease-free survival within the TCGA-STAD cohort. Further analysis revealed marked differences in CD8+ T cell infiltration and cytotoxic activity between the high and low cDC1 signature groups. Additionally, the high cDC1 signature group was strongly associated with upregulated expression of immune checkpoint proteins and the activation of oncogenic pathways, indicating a highly immunosuppressive tumor microenvironment. Conclusions: This study suggests that the cDC1-related gene signature may serve as a potent prognostic biomarker in gastric cancer, offering new insights into the complex interactions between the tumor and immune microenvironment. These results could pave the way for innovative therapeutic strategies that target the immune landscape in gastric cancer, potentially improving patient outcomes. Citation Format: Song-hee han. The Role of cDC1 Gene Signatures in gastric cancer prognosis and immune microenvironment modulation [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B028.

Endocervical Adenocarcinoma With Micropapillary Component, a Distinct Histological Subtype Associated With Aggressive Behavior and Poor Prognosis: A Clinicopathologic Study of 10 Patients.

Objective. Endocervical adenocarcinoma (ECA) with a micropapillary component is considered to be associated with aggressive behavior and poor prognosis. So far, only limited studies investigated this histological subtype of ECA in the literature. In this study, we present a clinicopathological analysis of 10 such tumors. Methods. We retrieved ten ECAs with a micropapillary component between January 2014 and July 2023 and analyzed their clinicopathologic features. Results. At diagnosis, nine tumors (90%) were of advanced clinical stage (FIGO stage ≥ IIA), nine tumors (90%) exhibited deep stromal invasion (≥2/3 of the cervix), and three tumors (30%) showed parametrial involvement. Lymphovascular invasion was evident in all tumors (100%), and lymph node metastasis was found in eight tumors (80%). Among the 10 patients, six were alive without disease (60%), one had a recurrent/later metastatic tumor (10%), and three died from the disease (30%). Furthermore, eight tumors were positive for PD-L1 expression (80%), while only one tumor showed HER2 overexpression (10%), and one tumor exhibited p53 mutant-type staining (10%). Conclusion. Endocervical adenocarcinomas with micropapillary components are associated with aggressive clinical behavior and a poor prognosis, which can be found in various conventional histological types of ECAs regardless of the HPV status. The high prevalence of PD-L1 expression suggests that patients with micropapillary ECAs may be good candidates for PD-L1 inhibitor treatment.

Origin tracking of Brucella strain B. melitensics bv.3 ARQ-070 using biochemical and genomic studies.

To conduct an origin tracking and genomic study of the Brucella strain B. melitensis bv.3 ARQ-070, with the aim of addressing the challenges posed by the highly conserved genome of Brucella to conventional typing methods and to gain an understanding of the geographic distribution and interspecies transmission of this pathogen in China. Differentiation and genotyping were established via biochemical profiles and polymerase chain reaction. Illumina MiSeq® was applied to sequence the Brucella isolates. Using multilocus sequence typing and Fisher's exact test was used for the KEGG enrichment analysis of differential genes. Differential gene protein-protein interaction (PPI) network analysis was conducted using the STRING database and visualization was performed using. According to the final identification results of an A/M serum agglutination test. ARQ-070 was identified as the No. 3 white spirulina biological variety, and mM was identified as the No. 1 white Spirulina biological variety. The genetic information of this strain is very close to that of the M5 vaccine strain, suggesting possible vaccine-escape infection. In the comparative genomics analysis with B. melitensis bv.1 16M, the main differences between the B. melitensis strains were found to be concentrated in the genes related to amino acid metabolism and environmental perception. A base mutation was found in the Brucella gene virB9, which is associated with the key virulence factor of the type IV secretion system, but this mutation did not lead to changes in the protein's tertiary structure, and the strain did not lose its infectivity. The study discovered a base mutation in the virB9 gene of Brucella, which is linked to T4SS but does not affect the protein's structure or the strain's infectivity. This mutation could influence public health approaches to detecting and preventing Brucella transmission. Future research aims to analyse a wider range of Brucella strains for a deeper understanding of their epidemiology.

IMMU-38. LEVERAGING INNATE IMMUNE SENSORS TO GENERATE DURABLE ANTI-GLIOMA ADAPTIVE IMMUNE RESPONSES

Abstract Glioblastoma harbors a tumor microenvironment (TME) that is mostly devoid of T cell effector infiltration but is dominated by immune suppressive microglia, macrophages, and myeloid-derived suppresser cells. The innate immune cells in the TME have impaired phagocytosis and antigen presentation and are inadequate for triggering the subsequent immune activating signals needed for anti-tumor effector responses. Phagocytic activity can also be blocked by the upregulation of CD47 on the tumor cells. In the immune checkpoint resistant Qki-/- Pten-/- P53-/- (QPP) glioma model, intratumoral treatment with the synthetic cyclic di-nucleotide STING agonist IACS-8803 (8803) induces global immunological reprogramming and long-term survival resistant to tumor rechallenge. More specifically, in the infiltrating myeloid stroma 8803 increases costimulatory protein CD86 while reducing the expression of suppressive markers CD163 and CD206. Conventional type 1 dendritic cells are increased in both the TME (p&amp;lt;0.05) and the draining cervical lymph node (p&amp;lt;0.01). Intratumoral infiltration of both CD8 T (p&amp;lt;0.05) and NK (p&amp;lt;0.001) cells increases. However, only T cells, but not NK cells, are necessary for 8803 therapeutic activity when assessed with in vivo NK cell depletion studies and treatment in the RAG-/- background. STING activation increases microglial phagocytic capacity, but also induces a compensatory increase in SIRPα expression (p&amp;lt;0.001) – the ligand for CD47. 8803 synergizes with anti-CD47 blockade to enhance microglia phagocytosis of QPP glioblastoma cells in vitro. Finally, the combination of 8803 and anti-CD47 synergizes to extend both median survival and the fraction of long-term survivors in orthotopic QPP-bearing mice (QPP8v; vehicle control MS=39d, anti-CD47 MS=40d, 8803 MS=67d 20% long-term survival, 8803 + anti-CD47 MS=107.5d 40% long-term survival). These data demonstrate that 8803 induces proinflammatory conversion of the glioblastoma TME, generates T cell-dependent survival benefits in QPP-bearing mice, and synergizes with anti-CD47 blockade to enhance microglia phagocytosis of glioblastoma cells and extend survival in QPP-bearing mice.

Combination CXCR4 and PD1 blockade enhances intratumoral dendritic cell activation and immune responses against hepatocellular carcinoma.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of unresectable hepatocellular carcinoma (HCC), but their impressive efficacy is seen in just a fraction of patients. One key mechanism of immunotherapy resistance is the paucity of dendritic cells (DCs) in liver malignancies. Here, we tested combination blockade of programmed death receptor 1 (PD1) and CXCR4, a receptor for CXCL12, a pleiotropic factor that mediates immunosuppression in tumors. Using orthotopic grafted and autochthonous HCC models with underlying liver damage, we evaluated treatment feasibility and efficacy. In addition, we examined the effects of treatment using immunofluorescence, flow cytometric analysis of DCs in vivo and in vitro, and RNA-sequencing. Combination anti-CXCR4 and anti-PD1therapy was safe and significantly inhibited tumor growth and prolonged survival in all murine preclinical models of HCC tested. The combination treatment successfully reprogrammed antigen-presenting cells, revealing the potential role of conventional type 1 DCs (cDC1s) in the HCC microenvironment. Moreover, DC reprogramming enhanced anticancer immunity by facilitating CD8+ T-cell accumulation and activation in the HCC tissue. The effectiveness of anti-CXCR4/PD1 therapy was compromised entirely in Batf3-KO mice deficient in cDC1s. Thus, combined CXCR4/PD1 blockade can reprogram intra-tumoral cDC1s and holds the potential to potentiate antitumor immune response against HCC.

Chemi-Impeditive Sensing Platform Based on Single-Walled Carbon Nanotubes.

Chemical sensing methodology based on electrochemical impedance spectroscopy (EIS) targeting analytes in aqueous samples on functionalized single-walled carbon nanotube (SWCNT) is reported. The SWCNT in contact with electrolyte shows unique impedance spectra that cannot be analyzed with classical equivalent circuit models. Inspired by the charge transport property of mixed ionic-electronic conductors, we propose an equivalent circuit based on transmission line model (TLM), by which the impedance of the CNT-electrolyte system can be analyzed to track down all the equivalent circuit parameters. By combining multiple pieces of information, which are technically immeasurable with conventional chemiresistive or chemicapacitive techniques, several analyte species responding to the sensor can be differentiated from each other. We demonstrate the "chemi-impeditive" concept on chemically modified SWCNTs for detecting perfluoroalkyl substances (PFAS) in aqueous solutions. The EIS coupled with a fluorination chemistry on SWCNT surface provides unique changes in equivalent circuit components for each PFAS, i.e., changes in CNT and solution resistances, as well as interfacial CNT-solution capacitance, through which perfluorooctanesulfonic acid, perfluorooctanoic acid, hexafluoropropylene oxide dimer acid, and perfluorobutanesulfonic acid are detected in a discriminative manner. The new impedimetric method opens up new vistas in chemical sensing in that the EIS analysis provides an additional dimension of information beyond the single resistance or capacitance typically measured by many conventional types of sensors.

Assessment and quantification of the microbial flora in the output water of two types of dental chairs: A comparative study

Objectives: Dental Unit Waterlines (DUWL) have shown to be a perfect host for different pathogenic microorganisms. The purpose of this study was to analyze and compare the level of bacterial contamination in the output water of 2 types of DUWL. Methods: Dental unit water samples from the air/water syringe of the A-dec (A-dec™ Performer 200, Newberg, USA) DUWL type and KaVo (ESTETICA™ E30/E70/E80 Vision, Kavo, Biberach, Germany) type were collected and analyzed for total aerobic flora, Pseudomonas aeruginosa, faecal coliforms, total coliforms, faecal streptococci and sulfite-reducing anaerobic flora. Results: The bacteriological analysis of water samples shows the presence of bacterial contamination at high levels exceeding the standard safety guidelines of 100 CFU/mL set up by the American Dental Association (ADA) and accepted by the Centers for Disease Control and prevention (CDC) on the heterotrophic bacterial load. The data shows no statistically significant differences for all bacteriological parameters studied between the conventional A-dec DUWL type and the KaVo type that has an automated mode of decontamination. Conclusions: Despite all the disinfecting solutions considered to eradicate the bacterial proliferation in DUWL, the problem remains one of the greatest challenges in modern dentistry. Practitioners and medical staff should not underestimate the harmful consequences of this bacterial growth, not only on the health of their patients but also on their own health.

Nrf2 Regulates Inflammation by Modulating Dendritic Cell-T Cell Crosstalk during Viral-Bacterial Superinfection.

Every year millions of people are infected with influenza, which can be complicated by secondary bacterial pneumonia. One factor that may contribute to increased susceptibility to secondary bacterial infection is the modulation of inflammatory cytokines. NF erythroid 2-related factor 2 (Nrf2) has been shown to be a master regulator of the antioxidant response and various inflammatory cytokines. To test the role of Nrf2 during viral-bacterial superinfection, we used a mouse model of influenza-Staphylococcus aureus superinfection with wild-type (WT) or Nrf2-deficient (Nrf2-/-) mice. Loss of Nrf2 reduced influenza burden and increased S. aureus burden during superinfection. Additionally, Nrf2-/- mice had increased abundance of conventional type 1 dendritic cells (DCs). We then tested the interaction between DCs and T cells using an invitro model of bone marrow-derived DCs with OVA and OT-II T cells. In this system, Nrf2-/- DCs promoted a Th2/regulatory T cell response as opposed to a Th1/Th17 response by WT DCs. This was recapitulated invivo with superinfected Nrf2-/- mice having increased regulatory T cell populations. We also observed an increased median survival time of Nrf2-/- superinfected mice, due at least in part to increased IL-10 signaling, as anti-IL-10R Ab treatment reduced median survival time to levels seen in WT mice. Overall, these data suggest that loss of Nrf2 promotes differential T cell skewing mediated by DCs that promote a regulatory phenotype, increasing superinfection survival time, despite increased bacterial burden.