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The use of Electronic Nicotine Delivery Systems (ENDS), or vaping devices, has raised concerns about their potential impact on oral health, particularly periodontal disease. While traditional smoking is a well-established risk factor for periodontal disease, the biological and microbial effects of ENDS use are less well understood. Our study examined how vaping and vaping behaviors influence the subgingival plaque microbiome and the associated metabolic pathways that may contribute to oral disease. We enrolled 70 healthy adults aged 18–35, including 48 regular ENDS users and 22 non-vaping controls. ENDS users were categorized by puffing behavior into low, medium, and high flow groups using a validated topography device. All participants underwent periodontal screening and provided saliva and subgingival plaque samples. To evaluate exposure profiles, ENDS users also submitted their personal devices for emissions testing, and volatile organic compounds (VOCs) were collected and analyzed using gas chromatography-mass spectrometry and high-performance liquid chromatography. Compared to non-vapers, ENDS users demonstrated distinct shifts in their oral microbiome, with reductions in beneficial taxa and increased bacteria associated with inflammation and periodontal disease. These changes were more pronounced in high-puff volume users, who also exhibited lower microbial diversity. Functional profiling revealed vaping-associated enrichment of pathways related to lipid metabolism, inflammation, and xenobiotic degradation. Untargeted salivary metabolomics identified metabolic disruptions consistent with these functional shifts. Integrative network analyses incorporating VOC measurements demonstrated correlations between microbial composition, puff volume, and metabolic disruptions, particularly in lipid-regulated and inflammatory pathways. To our knowledge, this is one of the first studies to integrate vaping behavior, oral microbiome profiling, salivary metabolomics, and VOC emissions analysis in a human cohort. These findings suggest ENDS use, especially at higher intensities, may disrupt oral microbial and metabolic homeostasis through both biological and chemical pathways potentially enhancing periodontal disease risk. These patterns point to potential biological and chemical pathways of concern, warranting further investigation and informing public health priorities.

The CRISPR-Cas13 system has been proposed as an alternative treatment of viral infections. However, for this approach to be adopted as an antiviral, it must be optimized until levels of efficacy rival or exceed the performance of conventional approaches. To take steps toward this goal, we evaluated the influenza viral RNA degradation patterns resulting from the binding and enzymatic activity of mRNA-encoded LbuCas13a and two crRNAs from a prior study, targeting PB2 genomic and messenger RNA. We found that the genome targeting guide has the potential for significantly higher potency than originally detected, because degradation of the genomic RNA is not uniform across the PB2 segment, but it is augmented in proximity to the Cas13 binding site. The PB2 genome targeting guide exhibited high levels (>1 log) of RNA degradation when delivered 24 hours post-infection in vitro and maintained that level of degradation over time, with increasing multiplicity of infection (MOI), and across modern influenza H1N1 and H3N2 strains. Chemical modifications to guides with potent LbuCas13a function, resulted in nebulizer delivered efficacy (>1–2 log reduction in viral titer) in a hamster model of influenza (Influenza A/H1N1/California/04/09) infection given prophylactically or as a treatment (post-infection). Maximum efficacy was achieved with two doses, when administered both pre- and post-infection. This work provides evidence that mRNA-encoded Cas13a can effectively mitigate Influenza A infections opening the door to the development of a programmable approach to treating multiple respiratory infections.

Periodontal disease in pregnancy is considered a risk factor for adverse birth outcomes. Periodontal disease has a microbial etiology, however, the current state of knowledge about the subgingival microbiome in pregnancy is not well understood. To characterize the structure and diversity of the subgingival microbiome in early and late pregnancy and explore relationships between the subgingival microbiome and preterm birth among pregnant Black women. This longitudinal descriptive study used 16S rRNA sequencing to profile the subgingival microbiome of 59 Black women and describe microbial ecology using alpha and beta diversity metrics. We also compared microbiome features across early (8-14 weeks) and late (24-30 weeks) gestation overall and according to gestational age at birth outcomes (spontaneous preterm, spontaneous early term, full term). In this sample of Black pregnant women, the top twenty bacterial taxa represented in the subgingival microbiome included a spectrum representative of various stages of biofilm progression leading to periodontal disease, including known periopathogens and Other organisms associated with periodontal disease reflected in the subgingival microbiome included several spp., and spp. Measures of alpha or beta diversity did not distinguish the subgingival microbiome of women according to early/late gestation or full term/spontaneous preterm birth; however, alpha diversity differences in late pregnancy between women who spontaneously delivered early term and women who delivered full term were identified. Several taxa were also identified as being differentially abundant according to early/late gestation, and full term/spontaneous early term births. Although the composition of the subgingival microbiome is shifted toward complexes associated with periodontal disease, the diversity of the microbiome remains stable throughout pregnancy. Several taxa were identified as being associated with spontaneous early term birth. Two, in particular, are promising targets of further investigation. Depletion of the oral commensal in early pregnancy and elevated levels of in late pregnancy were both associated with spontaneous early term birth.

The collection and order of nucleobases in a strand of DNA, called the primarysequence, is one of the most important pieces of information in the study of the humanbody. The proteins which regulate all biological functions in the body are synthesizedbased on the structure of the DNA molecule. The next generation sequencing (NGS)process of sequencing RNA transcripts, known as RNA-seq, has become a powerfulalternative to traditional microarray technology. NGS is used to measure the levels ofgene expression, detect structural DNA variations from the human reference genome,and uncover the epigenetic modifications of methylation. Despite its prevalence ingenetic research, RNA-seq data suffers from the statistical complication known as”large p small n” where the predictor variables greatly outnumber the subjects in astudy. In this research we propose combining all three types of data into amultivariate linear model. With the implementation of a variable selection processfor preliminary dimension reduction and the application of a Group LASSOapproach, we hope to reduce the complexity and dimension of NGS data to amanageable and, most importantly, interpretable level. Changes in gene expressionlevels have been linked with the development of harmful diseases such as cancer. Asuccessful model will provide insight on the simultaneous effects that methylationand structural variation have on gene expression in the body.

Dengue is a major global health threat, and there are no approved antiviral agents. Prior research using Cas13 only demonstrated dengue mitigation in vitro. Here we demonstrate that systemic delivery of mRNA-encoded Cas13a and guide RNAs formulated in lipid nanoparticles can be used to treat dengue virus (DENV) 2 and 3 in mice. First, we identified guides against DENV 2 and 3 that demonstrated in vitro efficacy. Next, we confirmed that Cas13 enzymatic activity is necessary for DENV 2 or DENV 3 mitigation in vitro. Last, we show that a single dose of lipid-nanoparticle-formulated mRNA-encoded Cas13a and guide RNA, administered 1 day post-infection, promotes survival of all infected animals and serum viral titre decreases on days 2 and 3 post-infection after lethal challenge in mice. Off-target analysis in mice using RNA sequencing showed no collateral cleavage. Overall, these data demonstrate the potential of mRNA-encoded Cas13 as a pan-DENV drug. Potent CRISPR guides targeting conserved dengue virus regions can treat dengue-2 and -3 infection in vivo in mice when co-delivered with Cas13 by lipid nanoparticles.

The acquisition of invasive properties is a prerequisite for tumor progression and metastasis. Molecular subtypes of KRAS-driven lung cancer exhibit distinct modes of invasion that likely contribute to unique growth properties and therapeutic susceptibilities. Despite this, pre-clinical discovery strategies designed to exploit invasive phenotypes are lacking. To address this, we designed an experimental system to screen for targetable signaling pathways linked to active early invasion phenotypes in the two most prominent molecular subtypes, TP53 and LKB1, of KRAS-driven lung adenocarcinoma (LUAD). By combining live-cell imaging of human bronchial epithelial cells in a 3D invasion matrix with RNA transcriptome profiling, we identified the LKB1-specific upregulation of bone morphogenetic protein 6 (BMP6). Examination of early-stage lung cancer patients confirmed upregulation of BMP6 in LKB1-mutant lung tumors. At the molecular level, we find that the canonical iron regulatory hormone Hepcidin is induced via BMP6 signaling upon LKB1 loss, where intact LKB1 kinase activity is necessary to maintain signaling homeostasis. Furthermore, pre-clinical studies in a novel Kras/Lkb1-mutant syngeneic mouse model show that potent growth suppression was achieved by inhibiting the ALK2/BMP6 signaling axis with single agents that are currently in clinical trials. We show that alterations in the iron homeostasis pathway are accompanied by simultaneous upregulation of ferroptosis protection proteins. Thus, LKB1 is sufficient to regulate both the 'gas' and 'breaks' to finely tune iron-regulated tumor progression.

Oncogenic RAS mutations drive aggressive cancers that are difficult to treat in the clinic, and while direct inhibition of the most common KRAS variant in lung adenocarcinoma (G12C) is undergoing clinical evaluation, a wide spectrum of oncogenic RAS variants together make up a large percentage of untargetable lung and GI cancers. Here we report that loss-of-function alterations (mutations and deep deletions) in the gene that encodes HD-PTP ( ) occur in up to 14% of lung cancers in the ORIEN Avatar lung cancer cohort, associate with adenosquamous histology, and occur alongside an altered spectrum of KRAS alleles. Furthermore, we show that in publicly available early-stage NSCLC studies loss of HD-PTP is mutually exclusive with loss of LKB1, which suggests they restrict a common oncogenic pathway in early lung tumorigenesis. In support of this, knockdown of HD-PTP in RAS-transformed lung cancer cells is sufficient to promote FAK-dependent invasion. Lastly, knockdown of the Drosophila homolog of HD-PTP (dHD-PTP/Myopic) synergizes to promote RAS-dependent neoplastic progression. Our findings highlight a novel tumor suppressor that can restrict RAS-driven lung cancer oncogenesis and identify a targetable pathway for personalized therapeutic approaches for adenosquamous lung cancer.

A field study was conducted in 2015 and 2016 to compare particle drift of glyphosate using a fluorescent tracer dye applied with hooded and open sprayers at four spray qualities (Fine [F], Medium [M], Very-Coarse [VC], and Ultra-Coarse [UC]). F and M spray qualities exhibited up to 86% and 56% less drift, respectively, out to 31 m downwind with the hooded sprayer than with the open sprayer. Conversely, VC and UC spray qualities were not affected by sprayer type out to 31m downwind. From 43 to 104m downwind, hooded sprayer applications exhibited approximately 50% less drift than open sprayer applications, regardless of spray quality. From 43 to 89m downwind, F spray qualities, regardless of sprayer type, exhibited higher drift than all other spray qualities. These data indicate that hooded sprayers considerably reduce drift of all spray qualities at short distances downwind. Additionally, at longer distances downwind, both larger spray qualities and sprayer hoods reduced drift independently. Nomenclature: Glyphosate

We report on the Bulge Asymmetries and Dynamic Evolution (BAaDE) survey which has observed 19 000 MSX color selected red giant stars for SiO maser emission at 43 GHz with the VLA and is in the process of observing 9 000 of these stars with ALMA at 86 GHz in the Southern sky. Our setup covers the main maser transitions, as well as those of isotopologues and selected lines of carbon-bearing species. Observations of this set of lines allow a far-reaching catalog of line-of-sight velocities in the dust-obscured regions where optical surveys cannot reach. Our preliminary detection rate is close to 70%, predicting a wealth of new information on the distribution of metal rich stars, their kinematics as function of location in the Galaxy, as well as the occurrence of lines and line ratios between the different transitions in combination with the spectral energy distribution from about 1 to 100 μ m. Similar to the OH/IR stars, a clear kinematic signature between disk and bulge stars can be seen. Furthermore, the SiO J = →10 ( v =3) line plays a prominent role in the derived maser properties.