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Langerhans cell histiocytosis (LCH) is a potentially fatal neoplasm characterized by the aberrant differentiation of mononuclear phagocytes, driven by mitogen-activated protein kinase (MAPK) pathway activation. LCH cells may trigger destructive pathology yet remain in a precarious state finely balanced between apoptosis and survival, supported by a unique inflammatory milieu. The interactions that maintain this state are not well known and may offer targets for intervention. Here, we used single-cell RNA-seq and protein analysis to dissect LCH lesions, assessing LCH cell heterogeneity and comparing LCH cells with normal mononuclear phagocytes within lesions. We found LCH discriminatory signatures pointing to senescence and escape from tumor immune surveillance. We also uncovered two major lineages of LCH with DC2- and DC3/monocyte-like phenotypes and validated them in multiple pathological tissue sites by high-content imaging. Receptor-ligand analyses and lineage tracing in vitro revealed Notch-dependent cooperativity between DC2 and DC3/monocyte lineages during expression of the pathognomonic LCH program. Our results present a convergent dual origin model of LCH with MAPK pathway activation occurring before fate commitment to DC2 and DC3/monocyte lineages and Notch-dependent cooperativity between lineages driving the development of LCH cells.

High water production in oil fields is an area of concern due to economic issues and borehole/wellhead damages. Colloidal gels can be a good alternative to polymers to address this as they can tolerate harsh oil reservoir conditions. A series of bottle tests with different silica and NaCl concentrations were first conducted. The gelation time, cation valence, rheology, and viscosity were investigated to characterize the gels. The applicability of solid gels in porous media was finally inspected in a dual-patterned glass micromodel. Bottle test results showed that increasing NaCl concentration at a constant silica concentration can convert solid gels into two-phase gels and then viscous suspensions. Na + replacement with Mg 2+ resulted a distinctive behaviour probably due to higher coagulating ability of Mg 2+ . Rheology and viscosity results agreed with gelation times: gel with shortest gelation time had the highest viscosity and storage/loss modulus but was not the most elastic one. Water injection into glass micromodel half-saturated with crude oil and solid gel proved that the gel is strong against pressure gradients applied by injected phase which is promising for water conformance controls. The diverted injected phase recorded an oil recovery of 53% which was not feasible without blocking the water zone., (© 2022. The Author(s).)

Animals use olfactory receptors to navigate mates, food, and danger. However, for complex olfactory systems, it is unknown what proportion of primary olfactory sensory neurons can individually drive avoidance or attraction. Similarly, the rules that govern behavioral responses to receptor combinations are unclear. We used optogenetic analysis in Drosophila to map the behavior elicited by olfactory-receptor neuron (ORN) classes: just one-fifth of ORN-types drove either avoidance or attraction. Although wind and hunger are closely linked to olfaction, neither had much effect on single-class responses. Several pooling rules have been invoked to explain how ORN types combine their behavioral influences; we activated two-way combinations and compared patterns of single- and double-ORN responses: these comparisons were inconsistent with simple pooling. We infer that the majority of primary olfactory sensory neurons have neutral behavioral effects individually, but participate in broad, odor-elicited ensembles with potent behavioral effects arising from complex interactions., Competing Interests: TT, SB, AK, JS, HC, AC No competing interests declared, (© 2022, Tumkaya et al.)

Personalized cancer vaccines are a promising approach for inducing T cell immunity to tumor neoantigens. Using a self-assembling nanoparticle vaccine that links neoantigen peptides to a Toll-like receptor 7/8 agonist (SNP-7/8a), we show how the route and dose alter the magnitude and quality of neoantigen-specific CD8 + T cells. Intravenous vaccination (SNP-IV) induced a higher proportion of TCF1 + PD-1 + CD8 + T cells as compared to subcutaneous immunization (SNP-SC). Single-cell RNA sequencing showed that SNP-IV induced stem-like genes (Tcf7, Slamf6, Xcl1) whereas SNP-SC enriched for effector genes (Gzmb, Klrg1, Cx3cr1). Stem-like cells generated by SNP-IV proliferated and differentiated into effector cells upon checkpoint blockade, leading to superior antitumor response as compared to SNP-SC in a therapeutic model. The duration of antigen presentation by dendritic cells controlled the magnitude and quality of CD8 + T cells. These data demonstrate how to optimize antitumor immunity by modulating vaccine parameters for specific generation of effector or stem-like CD8 + T cells.

Purpose: Chlorella vulgaris (CV) has exhibited immune-enhancing and protective activities against cancer and infections. However, there is an increasing concern about the use of Chlorella species in human, regarding its various molecules with antigenic features found in infectious microorganisms. Our goal was to investigate the impact of higher concentrations of CV on tumor growth in spontaneous mouse mammary tumor (SMMT) models., Methods: Balb/c mice were daily given CV powder at doses of 0, 200, or 300 mg/kg for 42 days (CONTROL, CV200, and CV300 groups, respectively; n = 6/group). On day 14, the SMMT was inoculated. Tumor volume (TV) and body weight (BW) were monitored on 5-day intervals following tumor challenge. On day 43, blood, spleen, lungs, and tumor tissues were collected. Histopathological examinations on lungs and tumor tissues were performed following hematoxylin-eosin staining. Intratumor expression of 27 genes was assessed by real-time PCR. Total IgG, IFNγ, and IL-4 levels in serum and spleen culture supernatant were measured by ELISA., Results: The TV/BW index showed significant increase in the CV200 group compared to the CONTROL (p = 0.047). The CV200 tumors exhibited more malignant phenotype, higher angiogenesis rate, and lower peritumoral neutrophil and macrophage-to-lymphocyte infiltration ratio compared to the CONTROL. Serum concentrations of IFNγ, IL-4, and IgG were declined, and the spleen IFNγ and IgG production was higher in the CV200 compared to the CONTROL. The IL-1β, IL-10, TGFβ1, FOXP3, HO-1, Gr1, CD11b, PCNA, LCN2, iNOS2, VEGFR2, CD31, and CD105L expressions were markedly increased in the CV200 tumors compared to the CONTROL (p = 0.001, 0.002, 0.006, 0.021, 0.004, 0.030, 0.016, 0.031, 0.025, 0.008, 0.014, 0.022, and 0.037, respectively). The changes in cytokine, IgG and gene expression values considerably correlated with tumor size, as well as with each other., Conclusions: Our data provided evidence that C. vulgaris at a specific dose (200 mg/kg) promoted tumor growth in a mammary tumor model. This consequence might reflect an immune derangement in favor of developing a protumor microenvironment. However, this hypothesis needs to be further investigated in future.

Transforming growth factor β1 (TGFβ1) is suggested to be involved in the pathogenesis of and in complications with breast cancer (BC). Polymorphisms in TGFβ1 gene (TGFβ1) have been suggested by many investigators to have a role in susceptibility to BC; however, many discordant data have been reported. Considering the role of ethnic variations, we performed an association study between TGFβ1 polymorphisms and BC among Iranian women. We sequenced DNA samples of 110 BC and 110 normal control women for the exons and their adjacent intronic regions of TGFβ1 using PCR. The allele, genotype, and haplotype frequencies were calculated using PowerMarker V3.25 and R 3.0.2 softwares. Ten single nucleotide polymorphisms (SNPs) were detected. Statistical analysis on the frequency of seven most frequent SNPs, including the three coding SNPs (cSNPs) revealed no significant difference between BC and control women. Moreover, among 11 constructed haplotypes, "GTGCCGC" was significantly different between two study groups. In conclusion, we found no association between the studied SNPs of TGFβ1 and BC among Iranian women, but a possible association between "GTGCCGC" haplotype and BC was seen. However, further studies are suggested to clarify this association.