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Immune cells harboring somatic mutations reportedly infiltrate cancer tissues in patients with solid cancers and accompanying clonal hematopoiesis. Loss‐of‐function TET2 mutations are frequently observed in clonal hematopoiesis in solid cancers. Here, using a mouse lung cancer model, we evaluated the activity of Tet2‐deficient immune cells in tumor tissues. Myeloid‐specific Tet2 deficiency enhanced tumor growth in mice relative to that seen in controls. Single‐cell sequencing analysis of immune cells infiltrating tumors showed relatively high expression of S100a8/S100a9 in Tet2‐deficient myeloid subclusters. In turn, treatment with S100a8/S100a9 promoted Vegfa production by cancer cells, leading to a marked increase in the tumor vasculature in Tet2‐deficient mice relative to controls. Finally, treatment of Tet2‐deficient mice with an antibody against Emmprin, a known S100a8/S100a9 receptor, suppressed tumor growth. These data suggest that immune cells derived from TET2‐mutated clonal hematopoiesis exacerbate lung cancer progression by promoting tumor angiogenesis and may provide a novel therapeutic target for lung cancer patients with TET2‐mutated clonal hematopoiesis. Our study suggests that immune cells derived from TET2‐mutated clonal hematopoiesis exacerbate lung cancer progression by promoting tumor angiogenesis. We present evidence that signaling through the S100a8/S100a9‐Emmprin‐Vegfa axis is essential for progression of a lung cancer model established in a microenvironment of Tet2‐deficient immune cells. Furthermore, we provide a novel target for lung cancer patients with accompanying TET2‐mutated clonal hematopoiesis.

Angioimmunoblastic T‐cell lymphoma (AITL) is an age‐related malignant lymphoma, characterized by immune system‐dysregulated symptoms. Recent sequencing studies have clarified the recurrent mutations in ras homology family member A (RHOA) and in genes encoding epigenetic regulators, tet methyl cytosine dioxygenase 2 (TET2), DNA methyl transferase 3 alpha (DNMT3A) and isocitrate dehydrogenase 2, mitochondrial (IDH2), as well as those related to the T‐cell receptor signaling pathway in AITL. In this review, we focus on how this genetic information has changed the understanding of the developmental process of AITL and will in future lead to individualized therapies for AITL patients. Recent progress in next‐generation sequencing has revealed the AITL specific genomic abnormalities in epigenetic regulators and TCR signaling. In this paper, we focused on the insights on how the biological and clinical aspects are linked to the genomic features of AITL.

We report fluxes and dry deposition velocities for 16 atmospheric compounds above a southeastern United States forest, including: hydrogen peroxide (H₂O₂), nitric acid (HNO₃), hydrogen cyanide (HCN), hydroxymethyl hydroperoxide, peroxyacetic acid, organic hydroxy nitrates, and other multifunctional species derived from the oxidation of isoprene and monoterpenes. The data suggest that dry deposition is the dominant daytime sink for small, saturated oxygenates. Greater than 6 wt %C emitted as isoprene by the forest was returned by dry deposition of its oxidized products. Peroxides account for a large fraction of the oxidant flux, possibly eclipsing ozone in more pristine regions. The measured organic nitrates comprise a sizable portion (15%) of the oxidized nitrogen input into the canopy, with HNO₃ making up the balance. We observe that water-soluble compounds (e.g., strong acids and hydroperoxides) deposit with low surface resistance whereas compounds with moderate solubility (e.g., organic nitrates and hydroxycarbonyls) or poor solubility (e.g., HCN) exhibited reduced uptake at the surface of plants. To first order, the relative deposition velocities of water-soluble compounds are constrained by their molecular diffusivity. From resistance modeling, we infer a substantial emission flux of formic acid at the canopy level (∼1 nmol m⁻²·s⁻¹). GEOS–Chem, awidely used atmospheric chemical transport model, currently underestimates dry deposition for most molecules studied in this work. Reconciling GEOS–Chem deposition velocities with observations resulted in up to a 45% decrease in the simulated surface concentration of trace gases.

Aqueous extracts of secondary organic aerosols (SOA) generated from the ozonolysis of d‐limonene were subjected to dissolution, evaporation, and re‐dissolution in the presence and absence of ammonium sulfate (AS). Evaporation with AS at pH 4–9 produced chromophores that were stable with respect to hydrolysis and had a distinctive absorption band at 500 nm. Evaporation accelerated the rate of chromophore formation by at least three orders of magnitude compared to the reaction in aqueous solution, which produced similar compounds. Absorption spectroscopy and high‐resolution nanospray desorption electrospray ionization (nano‐DESI) mass spectrometry experiments suggested that the molar fraction of the chromophores was small (<2%), and that they contained nitrogen atoms. Although the colored products represented only a small fraction of SOA, their large extinction coefficients (>105 L mol−1 cm−1 at 500 nm) increased the effective mass absorption coefficient of the residual organics in excess of 103 cm2 g−1 ‐ a dramatic effect on the optical properties from minor constituents. Evaporation of SOA extracts in the absence of AS resulted in the production of colored compounds only when the SOA extract was acidified to pH ∼ 2 with sulfuric acid. These chromophores were produced by acid‐catalyzed aldol condensation, followed by a conversion into organosulfates. The presence of organosulfates was confirmed by high resolution mass spectrometry experiments. Results of this study suggest that evaporation of cloud or fog droplets containing dissolved organics leads to significant modification of the molecular composition and serves as a potentially important source of light‐absorbing compounds. Key Points Evaporation of droplets generates organic compounds absorbing visible radiation Cloud cycling significantly changes the composition of organic aerosols

This study investigated long‐term chemical aging of model biogenic secondary organic aerosol (SOA) prepared from the ozonolysis of terpenes. Techniques including electrospray ionization mass spectrometry (ESI‐MS), UV‐visible spectroscopy, Fourier transform infrared (FTIR) spectroscopy, NMR, and three‐dimensional fluorescence were used to probe the changes in chemical composition of SOA collected by impaction on substrates and also of aqueous extracts of SOA. The addition of ammonium ions or amino acids to limonene SOA reproducibly produced orange‐colored species that strongly absorbed visible radiation and fluoresced at UV and visible wavelengths. Simultaneous addition of H2SO4 to the SOA aqueous extracts inhibited this color transformation. These observations suggest the existence of aging processes leading to heavily conjugated molecules containing organic nitrogen. The presence of nitrogen in the chromophores was confirmed by the dependence of the absorption and fluorescence spectra on the amino acids added. In contrast to the strong change in the absorption and fluorescence spectra, there was no significant change in the ESI‐MS, FTIR, and NMR spectra, suggesting that the chromophores were minor species in the aged SOA. Aqueous extracts of aged limonene + NH4+ SOA were characterized by an effective base‐e absorption coefficient of ∼3 L g−1 cm−1 at 500 nm. Assuming particulate matter concentrations typical of polluted rural air gives an upper limit of 0.2 M m−1 for the aerosol absorption coefficient due to the aged limonene oxidation products. Biogenic SOA can therefore become weakly absorbing if they undergo aging in the presence of NH4+‐containing aerosol.

The rapidly evolving market of disposable e-cigarettes poses unknown health risks to adolescents and young adults. We report excessive emissions of toxic metallic elements in aerosols from flavored and “clear” versions of three popular products (Esco Bar, Flum Pebble, and ELF Bar), orders of magnitude higher in concentration than traditional cigarettes and other e-cigarettes. Heating coil elements (chromium (Cr), nickel (Ni)) likely leached into e-liquids and aerosols from coil degradation during use, increasing up to 1000-fold in concentration over the device life. In Esco Bar devices, high concentrations of lead (Pb, ≤175 ppm), Ni (≤38 ppm), copper (Cu, ≤546 ppm), and zinc (Zn, ≤462 ppm) were observed in both e-liquids and aerosols. We identified the illicit use of leaded bronze in nonheating device components in contact with e-liquid as the source of Pb. Elevated antimony (Sb) in Flum Pebble and Esco Bar samples had unknown origins. Analyses showed Cr was present as nontoxic Cr­(III), while Sb was a mixture of nontoxic Sb­(V) and carcinogenic Sb­(III). Risk assessments revealed cancer risks from Ni and Sb­(III) and noncancer toxicity risks from Pb and Ni exceeded safety thresholds. These findings highlight critical gaps in e-cigarette regulation, characterization, and enforcement, with implications for public health.

The E‐cigarette or Vaping product‐Associated Lung Injury (EVALI) causes severe acute respiratory failure and, in some cases, death. Most cases are linked to tetrahydrocannabinol‐containing e‐cigarette products adulterated with vitamin E acetate. Despite regulation and awareness efforts, VEA persists in biological samples from EVALI patients and remains a public health concern, particularly among adolescent males. The mechanisms driving VEA‐induced lung injury, and how they may be differentiated by sex, remain poorly understood. To address this, age‐ and size‐matched adolescent male and female mice were exposed to aerosolized VEA for 3 or 10 days. By Day 10, VEA exposure caused histopathologic lung injury and systemic inflammation, with alveolar barrier dysfunction evident on Day 3. Male mice developed more severe injury and immune dysregulation, with elevated lung interleukin‐1β, interleukin‐6, and keratinocyte chemoattractant and reduced expression of club cell secretory protein along the airway epithelium. Female mice showed higher serum levels of soluble receptor for advanced glycation end products, a biomarker of alveolar injury and inflammation that also functions as an immune modulator. This is the first study to identify sex‐specific differences in pulmonary responses to VEA exposure. These findings offer insight into EVALI immunopathogenesis and may explain population‐level sex disparities in disease severity.

Owing to their pleiotropic metabolic benefits, glucagon-like peptide-1 receptor (GLP-1R) agonists have been successfully utilized for treating metabolic diseases, such as type 2 diabetes and obesity. As part of our efforts in developing long-acting peptide therapeutics, we have previously reported a peptide engineering strategy that combines peptide side chain stapling with covalent integration of a serum protein-binding motif in a single step. Herein, we have used this strategy to develop a second generation extendin-4 analog rigidified with a symmetrical staple, which exhibits an excellent in vivo efficacy in an animal model of diabetes and obesity. To simplify the scale-up manufacturing of the lead GLP-1R agonist, a semisynthesis protocol was successfully developed, which involves recombinant expression of the linear peptide followed by attachment of a polyethylene glycol (PEG)-fatty acid staple in a subsequent chemical reaction step.

Background Mitochondrial disorders are difficult to diagnose due to extreme genetic and phenotypic heterogeneities. Methods We explored the utility of targeted next-generation sequencing for the diagnosis of mitochondrial disorders in 148 patients submitted for clinical testing. A panel of 447 nuclear genes encoding mitochondrial respiratory chain complexes, and other genes inducing secondary mitochondrial dysfunction or that cause diseases which mimic mitochondrial disorders were tested. Results We identified variants considered to be possibly disease-causing based on family segregation data and/or variants already known to cause disease in twelve genes in thirteen patients. Rare or novel variants of unknown significance were identified in 45 additional genes for various metabolic, genetic or neurogenetic disorders. Conclusions Primary mitochondrial defects were confirmed only in four patients indicating that majority of patients with suspected mitochondrial disorders are presumably not the result of direct impairment of energy production. Our results support that clinical and routine laboratory ascertainment for mitochondrial disorders are challenging due to significant overlapping non-specific clinical symptoms and lack of specific biomarkers. While next-generation sequencing shows promise for diagnosing suspected mitochondrial disorders, the challenges remain as the underlying genetic heterogeneity may be greater than suspected and it is further confounded by the similarity of symptoms with other conditions as we report here.