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Chronic obstructive pulmonary disease (COPD) is associated with age and smoking, but other determinants of the disease are incompletely understood. Clonal hematopoiesis of indeterminate potential (CHIP) is a common, age-related state in which somatic mutations in clonal blood populations induce aberrant inflammatory responses. Patients with CHIP have an elevated risk for cardiovascular disease, but the association of CHIP with COPD remains unclear. We analyzed whole-genome sequencing and whole-exome sequencing data to detect CHIP in 48 835 patients, of whom 8444 had moderate to very severe COPD, from four separate cohorts with COPD phenotyping and smoking history. We measured emphysema in murine models in which Tet2 was deleted in hematopoietic cells. In the COPDGene cohort, individuals with CHIP had risks of moderate-to-severe, severe, or very severe COPD that were 1.6 (adjusted 95% confidence interval [CI], 1.1-2.2) and 2.2 (adjusted 95% CI, 1.5-3.2) times greater than those for noncarriers. These findings were consistently observed in three additional cohorts and meta-analyses of all patients. CHIP was also associated with decreased FEV1% predicted in the COPDGene cohort (mean between-group differences, −5.7%; adjusted 95% CI, −8.8% to −2.6%), a finding replicated in additional cohorts. Smoke exposure was associated with a small but significant increased risk of having CHIP (odds ratio, 1.03 per 10 pack-years; 95% CI, 1.01-1.05 per 10 pack-years) in the meta-analysis of all patients. Inactivation of Tet2 in mouse hematopoietic cells exacerbated the development of emphysema and inflammation in models of cigarette smoke exposure. Somatic mutations in blood cells are associated with the development and severity of COPD, independent of age and cumulative smoke exposure.

In this paper, general logic cell and module designs in basic digital signal processing (DSP), for transparent, flexible chips and wearable electronics are presented. Modified Circuits from ratioed logic and pass transistor logic styles are modified and proposed, based on n-type-only indium tin oxide (ITO) stabilized ZnO thin-film transistors (TFTs) process. Elaborations on logic circuits with purely n-type TFT transistors were carried out to extend the logic swing of circuit outputs and accelerate the signal propagation in complex logic functions with simplified pull-up/pull-down or passive networks. To implement logic complexes on multiple OR-of-ANDs functions with better performance, tailored active controlled ratioed logic style is adopted with faster speed and smaller area by simplifying the transistor networks properly. All the circuits were fabricated on transparent glass plate. The featured 2-input/3-input XOR gate, 4-1 MUX and D flip flop (DFF) can operate with maximum featured delays of 2-6 μs at 5 V power supply, with comparatively over 50% less delays and areas than other state-of-art works. The featured 4-bit adder performs maximum 16.41 μs delay at 5 V in measurement. A 4-bit multiplier is also presented based on the adder and DFF. These proposed TFT circuits exhibited smaller area with relatively moderate-high performance in comparison, which were promising building blocks for transparent flexible DSP electronics with low-speed requirements.

Supplementary Excel File 19 from Functional Synergies yet Distinct Modulators Affected by Genetic Alterations in Common Human Cancers

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ImportanceCurrently, predictive biomarkers for response to immune checkpoint inhibitor (ICI) therapy in lung cancer are limited. Identifying such biomarkers would be useful to refine patient selection and guide precision therapy.ObjectiveTo develop a machine-learning (ML)-based tumor-infiltrating lymphocytes (TILs) scoring approach, and to evaluate TIL association with clinical outcomes in patients with advanced non–small cell lung cancer (NSCLC).Design, Setting, and ParticipantsThis multicenter retrospective discovery-validation cohort study included 685 ICI-treated patients with NSCLC with median follow-up of 38.1 and 43.3 months for the discovery (n = 446) and validation (n = 239) cohorts, respectively. Patients were treated between February 2014 and September 2021. We developed an ML automated method to count tumor, stroma, and TIL cells in whole-slide hematoxylin-eosin–stained images of NSCLC tumors. Tumor mutational burden (TMB) and programmed death ligand-1 (PD-L1) expression were assessed separately, and clinical response to ICI therapy was determined by medical record review. Data analysis was performed from June 2021 to April 2022.ExposuresAll patients received anti–PD-(L)1 monotherapy.Main Outcomes and MeasuresObjective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were determined by blinded medical record review. The area under curve (AUC) of TIL levels, TMB, and PD-L1 in predicting ICI response were calculated using ORR.ResultsOverall, there were 248 (56%) women in the discovery cohort and 97 (41%) in the validation cohort. In a multivariable analysis, high TIL level (≥250 cells/mm2) was independently associated with ICI response in both the discovery (PFS: HR, 0.71; P = .006; OS: HR, 0.74; P = .03) and validation (PFS: HR = 0.80; P = .01; OS: HR = 0.75; P = .001) cohorts. Survival benefit was seen in both first- and subsequent-line ICI treatments in patients with NSCLC. In the discovery cohort, the combined models of TILs/PD-L1 or TMB/PD-L1 had additional specificity in differentiating ICI responders compared with PD-L1 alone. In the PD-L1 negative (Conclusions and RelevanceIn these cohorts, TIL levels were robustly and independently associated with response to ICI treatment. Patient TIL assessment is relatively easily incorporated into the workflow of pathology laboratories at minimal additional cost, and may enhance precision therapy.

The study addresses the effects of Al2O3 on the SiC coating fabricated by pack cementation by preparing coatings with different Al2O3 contents on C/C composite. After the in-depth analysis of various characterization results, including XRD, SEM, EDS, and XPS, the competition brought by Al2O3 between enhancing coatings qualities and affecting oxidation behaviors was revealed. One insight into the microstructure of as-prepared coatings is that Al2O3 could boost internal exchange and the diffusion of parent materials, which is conducive to resisting oxidation by improving the qualities of the layers. Another insight about the coating oxidation is obtained from the SiC–Al2O3 volatility diagram, where the multiple roles of Al2O3 plays in the transition of oxidative mechanisms are elucidated. The beneficial impact that stables the oxide layer and reduces the coating consumption takes the upper hand comparing to the adverse effect, including breaking the structure of SiO2.

Ectopic pancreas within the anterior mediastinum is a rare congenital anomaly. We present a case of a solid anterior mediastinal mass that presented with hemoptysis and ground glass parenchymal changes in the right upper lobe. Robotic surgical resection was completed, and final pathology was consistent with benign pancreatic tissue. The patient fully recovered with no recurrence of hemoptysis. Ectopic pancreas, although uncommon, should be included in the differential for solid and cystic anterior mediastinal masses, and surgical resection is often curative and effectively manages symptoms.

Background To improve the utilization rate of cinnamon essential oil and compensate for the shortcomings of its easy decomposition and oxidation, the microemulsion of cinnamon essential oil was prepared using Tween 80 and anhydrous ethanol as surfactant and cosurfactant, respectively. The effects of the surfactant type, Km value, preparation temperature and aqueous pH on the quality of the microemulsion were studied via a pseudo-ternary phase diagram. The slow-release performance of cinnamon essential oil microemulsion and the control performance of the insect repellent package on the rice weevil were characterized. Results The results showed that, when Tween 80 was used as a surfactant and anhydrous ethanol was used as a cosurfactant, the Km value was 3:1, preparation temperature was 40 °C, aqueous pH was 5 and prepared cinnamon essential oil microemulsion was of the O/W type. The microemulsion had strong stability and a 81.5-nm concentrated particle size distribution, and possessed excellent embedding and sustained-release effects. The prepared insect repellent active package prolongs the use time and the effect of cinnamon essential oil. The repellent rate of the rice weevil was as high as 100% after 48 h, and the contact mortality and fumigation mortality rates of the rice weevil also reached 96.67% and 86.67%, respectively, after 96 h. Conclusion The prepared cinnamon essential oil microemulsion and active packaging had a good sustained-release effect. © 2021 Society of Chemical Industry.

It has recently been demonstrated that harps harvest substantively more fog water than conventional mesh nets, but the optimal design for fog harps remains unknown. Here, we systematically vary key parameters of a scale-model fog harp, the wire material, wire pitch, and wire length, to find the optimal combination. We found stainless steel to not only be the best hydrophilic wire material but also nearly be as effective as Teflon-coated wires. The best choice for the wire pitch was coupled to the wire length, as the smallest pitch collected the most water for short harps but was hampered by tangling for taller harps. Accordingly, we use an elastocapillary wire tangling model to successfully predict the onset of tangling beyond a critical length for any given wire pitch. Combining what we learned, we achieved a water harvesting efficiency of 17% with an optimized stainless-steel harp, over three times higher than that of the current standard of a Raschel mesh. These results suggest that an optimal fog harp should feature high-tension, uncoated wires within a large aspect ratio frame to avoid tangling and promote efficient and reliable fog harvesting.

Bone marrow mesenchymal stem cell-derived small extracellular vesicles (BMSC-sEVs) can be used as a potential cell-free strategy for periodontal tissue regeneration, and we aim to investigate the effect and possible mechanism of BMSC-sEV in periodontal tissue regeneration in this study. The BMSC-sEV was isolated by the Exosome Isolation™ reagent and identified by transmission electron microscopy, nanoparticle tracking analysis, and Western blotting. The human periodontal ligament cells (hPDLCs) were cocultured with BMSC-sEV

To add value to ordinary kitchen waste, heterogeneous acid-base catalytic methanolysis was conducted to produce high-value liquid biofuels, methyl levulinate (ML) and fatty acid methyl esters (FAMEs). Yields of 53.3 % ML and 98.5 % FAME were achieved by methanolysis of kitchen waste under the co-catalysis of carbon-silica composite (C/Si-SO

It is increasingly recognized that the cellular microenvironment plays critical roles in regulating the fate and physiology of cells. Despite recent advancements in single-cell analysis technologies, engineering and integration of the microenvironment for single-cell analysis platforms remain limited. Here, we report a single-cell cytokine secretion analysis platform that integrated both the three-dimensional cell culture and the primary oral squamous cell carcinoma tumor cell co-culture to provide both physical and physiological cues for single cells to be analyzed. We apply the platform to investigate the immune responses of human macrophages stimulated with the ligand of toll-like receptor 4 lipopolysaccharide. Notably, we observe the differential modulation effect in cytokine secretions by the tumor microenvironment, in which antitumor cytokine TNF-a secretion was attenuated, and protumor cytokine IL-6 would increase. The differential modulation effect is conserved from cell line-derived macrophages to primary macrophages derived from healthy donors. Immunofluorescence staining further reveals that ∼50% of macrophage cells could be polarized from M1 to the M2 phenotype within 12 h in the engineered tumor microenvironment. This work demonstrates the significance of the cell microenvironment toward single-cell analysis, which could help to evaluate how immune cells will respond in the complex microenvironment more accurately.

Purpose The purpose of this paper is to prepare Ti(C,N) coatings on TA15 treated and not treated by shot peening using double glow plasma alloying technique. The effect of shot peening on the wear behavior of Ti(C,N) coatings is discussed. Design/methodology/approach The Ti(C,N) coatings were prepared by double glow plasma alloying technique on two different TA15 substrate; one is shot peened and the other is not. Findings Ti(C,N) coating on SP-treated TA15 was thicker and denser, and the grain size was smaller compared with that on original TA15. Compared with the Ti(C,N) coating on original TA15, the wear resistance of that on SP-treated TA15 is improved. Ti(C,N) coating on SP-treated TA15 showed higher nanohardness and bearing capacity than that on original TA15. Originality/value For double glow plasma alloying technique, surface quality, surface activity and other factors will have influence on the thickness and density of the coating. The wear mechanisms of Ti(C,N) coating on original TA15 are serious abrasive wear and oxidation wear. However, the wear mechanism of Ti(C,N) coating on SP-treated TA15 is slightly oxidation wear. Peer review The peer review history for this article is available at: https://publons.com/publon/10.1108/ILT-07-2020-0283/

Tumor-infiltrating immune cells (TICs) can serve as an important indicator to evaluate the prognosis and therapeutic response in lung adenocarcinoma (LUAD). The identification of mutated genes that can affect the abundance of TICs and prognosis has practical implications. In the presented study, tumor microenvironment (TME) scoring was performed by the ESTIMATE scoring system on 598 RNA transcripts selected from the TCGA database to determine the proportions of immune cells and stromal cells. The infiltration difference of TICs in LUAD samples was obtained by CIBERSORT. The ‘immuneeconv’ R software package, which integrates six latest algorithms, including TIMER, xCell, MCP-counter, CIBERSORT, EPIC and quanTIseq were used to verify the correlation between purinergic receptor P2Y13 (P2RY13) and immune cells. Based on RNA sequencing analysis of the Lewis lung cancer-bearing model in C57BL/6 mice and immunohistochemistry (IHC) of human LUAD tissues, the expression of P2RY13 and associated pathways were verified. It was shown that differentially expressed genes (DEGs) obtained by interactive analysis based on Immunescore and Stromalscore were significantly enriched in immune-related pathways. The expression of P2RY13 was significantly associated with prognosis and clinicopathological characteristics of LUAD patients. More importantly, this gene played an important role in maintaining the immune dominant environment and changing the regulation of TICs. P2RY13 expression was positively correlated with the infiltration of dendritic cells (DCs) in various of tumor tissues as validated by the PanglaoDB scRNA-seq database. Therefore, P2RY13 is expected to be a potential biomarker for predicting TME and the prognosis of LUAD after verification., GRAPHICAL ABSTRACT