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To address the challenges faced by vehicles during actual operation when passing through traffic lights or intersections, where rapid changes in operating conditions can lead to a decrease in SCR efficiency and an increase in NOx emissions, this study focuses on defining characteristic position scenarios and analyzing the NOx emission characteristics of vehicles when passing through these scenarios based on real-time vehicle conditions. Through the analysis of several specific events, several road condition factors and driver behavior factors that may contribute to increased NOx emissions at characteristic position scenarios are identified. The findings indicate that when vehicles pass through traffic lights and intersections, the main causes of increased NOx emissions are low SCR temperature resulting from prolonged idling or engine shutdown, and high exhaust NOx emissions resulting from sudden excessive fuel injection. The driver behaviors associated with these situations primarily include coasting when approaching intersections, frequent stop-start behaviour due to traffic congestion or road crowding, choosing to shut off the engine for fuel efficiency during prolonged traffic congestion, and aggressive acceleration by stepping on the accelerator when the green light is about to turn red.

Codon optimality has been demonstrated to be an important determinant of mRNA stability and expression levels in multiple model organisms and human cell lines. However, tissue-specific codon optimality has not been developed to investigate how codon optimality is usually perturbed by somatic synonymous mutations in human cancers. Here, we determined tissue-specific codon optimality in 29 human tissues based on mRNA expression data from the Genotype-Tissue Expression project. We found that optimal codons were associated with differentiation, whereas non-optimal codons were correlated with proliferation. Furthermore, codons biased toward differentiation displayed greater tissue specificity in codon optimality, and the tissue specificity of codon optimality was primarily present in amino acids with high degeneracy of the genetic code. By applying tissue-specific codon optimality to somatic synonymous mutations in 8532 tumor samples across 24 cancer types and to those in 416 normal cells across six human tissues, we found that synonymous mutations frequently increased optimal codons in tumor cells and cancer-related genes (e.g., genes involved in cell cycle). Furthermore, an elevated frequency of optimal codon gain was found to promote tumor cell proliferation in three cancer types characterized by DNA damage repair deficiency and could act as a prognostic biomarker for patients with triple-negative breast cancer. In summary, this study profiled tissue-specific codon optimality in human tissues, revealed alterations in codon optimality caused by synonymous mutations in human cancers, and highlighted the non-negligible role of optimal codon gain in tumorigenesis and therapeutics.

Background: Intratumor heterogeneity (ITH) has been shown to be inversely associated with immune infiltration in several cancers including clear cell renal cell carcinoma (ccRCC), but it remains unclear whether ITH is associated with response to immunotherapy (e.g. PD-1 blockade) in ccRCC. Methods: We quantified ITH using mutant-allele tumor heterogeneity, investigated the association of ITH with immune parameters in patients with ccRCC ( n = 336) as well as those with papillary RCC (pRCC, n = 280) from The Cancer Genome Atlas, and validations were conducted in patients with ccRCC from an independent cohort ( n = 152). The relationship between ITH and response to anti-PD-1 immunotherapy was explored in patients with metastatic ccRCC from a clinical trial of anti-PD-1 therapy ( n = 35), and validated in three equal-size simulated data sets ( n = 60) generated by random sampling with replacement based on this clinical trial cohort. Results: In ccRCC, low ITH was associated with better survival, more reductions in tumor burden, and clinical benefit of anti-PD-1 immunotherapy through modulating immune activity involving more neoantigens, elevated expression of HLA class I genes, and higher abundance of dendritic cells. Furthermore, we found that the association between the level of ITH and response to PD-1 blockade was independent of the mutation status of PBRM1 and that integrating both factors performed better than the individual predictors in predicting the benefit of anti-PD-1 immunotherapy in ccRCC patients. In pRCC, increased immune activity was also observed in low- versus high-ITH tumors, including higher neoantigen counts, increased abundance of monocytes, and decreased expression of PD-L1 and PD-L2. Conclusions: ITH may be helpful in the identification of patients who could benefit from PD-1 blockade in ccRCC, and even in pRCC where no genomic metrics has been found to correlate with response to immune checkpoint inhibitors.

Nanomaterials have been widely used in biomedical sciences; however, the mechanism of interaction between nanoparticles and biomolecules is still not fully understood. In the present study, we report the interaction mechanism between differently sized Ag nanoparticles and the improved light-oxygen-voltage (iLOV) protein. The steady-state and time-resolved fluorescence results demonstrated that the fluorescence intensity and lifetime of the iLOV protein decreased upon its adsorption onto Ag nanoparticles, and this decrease was dependent upon nanoparticle size. Further, we showed that the decrease of fluorescence intensity and lifetime arose from electron transfer between iLOV and Ag nanoparticles. Moreover, through point mutation and controlled experimentation, we demonstrated for the first time that electron transfer between iLOV and Ag nanoparticles is mediated by the tryptophan residue in the iLOV protein. These results are of great importance in revealing the function of iLOV protein as it applies to biomolecular sensors, the field of nano-photonics, and the interaction mechanism between the protein and nanoparticles.

Dilution is considered to be a fast and easily applicable pretreatment for anaerobic digestion (AD) of chicken manure (CM), however, dilution with fresh water is uneconomical because of the water consumption. The present investigation was targeted at evaluating the feasibility and process performance of AD of CM diluted with algal digestate water (AW) for methane production to replace tap water (TW). Moreover, the kinetics parameters and mass flow of the AD process were also comparatively analyzed. The highest methane production of diluted CM (104.39 mL/g volatile solid (VS)) was achieved with AW under a substrate concentration of 8% total solid (TS). The result was markedly higher in comparison with the group with TW (79.54–93.82 mL/gVS). Apart from the methane production, considering its energy and resource saving, nearly 20% of TW replaced by AW, it was promising substitution to use AW for TW to dilute CM. However, the process was susceptible to substrate concentration, inoculum, as well as total ammonia and free ammonia concentration.

Hypertrophic scarring, a common proliferative disorder of dermal fibroblasts, results from an overproduction of fibroblasts and excessive deposition of collagen. Although treatment with surgical excision or steroid hormones can modify the symptoms, numerous treatment-related complications have been described. In view of this, we investigated the therapeutic effects of essential oil (EO) from rhizomes of Ligusticum chuanxiong Hort. (Umbelliferae) on formed hypertrophic scars in a rabbit ear model. EO was prepared as a liposomal formulation (liposome-enveloped essential oil, LEO) and a rabbit ear model with hypertrophic scars was established. LEO (2.5, 5, and 10%) was applied once daily to the scars for 28 days. On postoperative day 56, the scar tissue was excised for masson's trichrome staining, detection of fibroblast apoptosis, assays of the levels of collagens I and III, and analysis of the mRNA expression of matrix metalloproteinase-1 (MMP-1), caspase-3 and -9, and transforming growth factor beta 1 (TGF-β(1)). In addition, the scar elevation index (SEI) was also determined. As a result, LEO treatment significantly alleviated formed hypertrophic scars on rabbit ears. The levels of TGF-β(1), MMP-1, collagen I, and collagen III were evidently decreased, and caspase -3 and -9 levels and apoptosis cells were markedly increased in the scar tissue. SEI was also significantly reduced. Histological findings exhibited significant amelioration of the collagen tissue. These results suggest that LEO possesses the favorable therapeutic effects on formed hypertrophic scars in the rabbit ear model and may be an effective cure for human hypertrophic scars.

Herein, we have described a novel organocatalytic approach to access biologically important dihydropyridin-2-ones in a one-pot way with generally high yields (up to 99%) and excellent enantioselectivities (up to 99% ee). This reaction proceeded via a new dual activation mode, including in situ-generated α,β-unsaturated acylazoliums and 4-dimethylaminopyridinium salts that underwent a Michael addition/1,4-H migration/lactamization sequence. The base-triggered 4-dimethylaminopyridinium ylide formation pathway over the competing substitution reaction pathway of vicinal haloamines is noteworthy. [ABSTRACT FROM AUTHOR]