Detecting volatile organic compounds (VOCs) in exhaled breath is a promising research area for disease diagnosis. Mass transfer behavior plays a crucial role in determining the detection performance ...of VOCs. However, the high mobility of exhaled breath poses a substantial challenge for the mass transfer process. Here, the distinct mass transfer behavior of mobile gaseous molecules is discovered by employing the schlieren imaging technique to visualize gas flow. The results demonstrate that hollow porous structures exhibit a higher gas flow flux than solid film and microporous structures, thereby generating a sufficient probability of contact reactions for mobile gaseous molecules. The proposed colorimetric array sensors offer enhanced sensitivity and stability for detecting mobile gaseous molecules. The discovery will serve as a foundational milestone is anticipated in elucidating the behavior of gas mass transfer and promoting its potential application in disease detection through the analysis of human exhaled breath.
The analysis of volatile organic compounds (VOCs) in exhaled breath is expected to be used for disease diagnosis and health monitoring. The schlieren imaging technique of gas flow is employed to elucidate the mass transfer behavior of mobile gas across various structures. The hollow porous structures significantly enhance the flux of gas transport, improving the visualized results and detected sensitivity of colorimetric array sensors CASs.
Flowering plants (angiosperms) are dominant components of global terrestrial ecosystems, but phylogenetic relationships at the familial level and above remain only partially resolved, greatly ...impeding our full understanding of their evolution and early diversification. The plastome, typically mapped as a circular genome, has been the most important molecular data source for plant phylogeny reconstruction for decades.
Here, we assembled by far the largest plastid dataset of angiosperms, composed of 80 genes from 4792 plastomes of 4660 species in 2024 genera representing all currently recognized families. Our phylogenetic tree (PPA II) is essentially congruent with those of previous plastid phylogenomic analyses but generally provides greater clade support. In the PPA II tree, 75% of nodes at or above the ordinal level and 78% at or above the familial level were resolved with high bootstrap support (BP ≥ 90). We obtained strong support for many interordinal and interfamilial relationships that were poorly resolved previously within the core eudicots, such as Dilleniales, Saxifragales, and Vitales being resolved as successive sisters to the remaining rosids, and Santalales, Berberidopsidales, and Caryophyllales as successive sisters to the asterids. However, the placement of magnoliids, although resolved as sister to all other Mesangiospermae, is not well supported and disagrees with topologies inferred from nuclear data. Relationships among the five major clades of Mesangiospermae remain intractable despite increased sampling, probably due to an ancient rapid radiation.
We provide the most comprehensive dataset of plastomes to date and a well-resolved phylogenetic tree, which together provide a strong foundation for future evolutionary studies of flowering plants.
The world's herbaria contain millions of specimens, collected and named by thousands of researchers, over hundreds of years. However, this treasure has remained largely inaccessible to genetic ...studies, because of both generally limited success of DNA extraction and the challenges associated with PCR-amplifying highly degraded DNA. In today's next-generation sequencing world, opportunities and prospects for historical DNA have changed dramatically, as most NGS methods are actually designed for taking short fragmented DNA molecules as templates.
As a practical test of routine recovery of rDNA and plastid genome sequences from herbarium specimens, we sequenced 25 herbarium specimens up to 80 years old from 16 different Angiosperm families. Paired-end reads were generated, yielding successful plastid genome assemblies for 23 species and nuclear rDNAs for 24 species, respectively. These data showed that genome skimming can be used to generate genomic information from herbarium specimens as old as 80 years and using as little as 500 pg of degraded starting DNA.
The routine plastome sequencing from herbarium specimens is feasible and cost-effective (compare with Sanger sequencing or plastome-enrichment approaches), and can be performed with limited sample destruction.
The adsorption of chromium (VI) ions from aqueous solution by ethylenediamine-modified cross-linked magnetic chitosan resin (EMCMCR) was studied in a batch adsorption system. Chromium (VI) removal is ...pH dependent and the optimum adsorption was observed at pH 2.0. The adsorption rate was extremely fast and the equilibrium was established within 6–10
min. The adsorption data could be well interpreted by the Langmuir and Temkin model. The maximum adsorption capacities obtained from the Langmuir model are 51.813
mg
g
−1, 48.780
mg
g
−1 and 45.872
mg
g
−1 at 293, 303 and 313
K, respectively. The adsorption process could be described by pseudo-second-order kinetic model. The intraparticle diffusion study revealed that film diffusion might be involved in the present case. Thermodynamic parameters revealed the feasibility, spontaneity and exothermic nature of adsorption. The sorbents were successfully regenerated using 0.1
N NaOH solutions.
The response to immune checkpoint inhibitors (ICIs) monotherapy remains unsatisfactory in patients with NSCLC. Thus, combining ICIs with other potential modalities is of great significance to enhance ...the response of single drug alone. Here, we identified that HIF-1α inhibition was capable of promoting anti-tumor immunity in NSCLC. We applied NSCLC cell lines and mouse models to evaluate the synergy of combined HIF-1α inhibition and PD-1 blockade on tumor growth and the function of tumor infiltrating lymphocytes (TILs). Public datasets were utilized to investigate patients' prognosis based on expressions of HIF-1α and LOXL2 as well as EMT-associated markers and CD8+ TILs. Moreover, we explored the correlation between HIF-1α and LOXL2 levels and CD8+ TILs in tumor samples from patients with NSCLC by immunohistochemistry, as well as their association to patients’ survival. In vitro, PX-478, an HIF-1α inhibitor, promoted tumor cell apoptosis induced by T cells when combined with ICIs. Furthermore, mice treated with PX-478 and anti-PD-1 antibodies exhibited a marked delay in tumor growth and prolonged survival, which correlated with increased TILs and granzyme B secretion. Besides, patients with high HIF-1α expression exhibited high levels of EMT-related markers and low TILs, indicating an immunosuppressive phenotype. Mechanistically, we observed that HIF-1α inhibition suppressed the EMT phenotypes induced by hypoxia and further alleviated tumor immunosuppression, which was related to blockage of HIF-1α/LOXL2 signaling pathway. In summary, we identified that HIF-1α inhibition could synergize with anti-PD-1 to impair tumor growth in vitro and in vivo. Our data suggest that HIF-1α inhibitors represent a promising treatment to enhance anti-tumor immunity and provide preclinical rationale to evaluate the combination of ICIs with HIF-1α inhibition clinically in NSCLC.
•Attenuating hypoxia-induced EMT phenotypes may increase tumor infiltrated activating T cells.•Downregulation of EMT by HIF-1α inhibition was associated with suppression of the HIF-1α-LOXL2 signaling pathway.•The combination of HIF-1α inhibition and ICIs can induce significant tumor regression and improve efficacy of immunotherapy.
Colon cancer is the third most common cancer and the second leading cause of cancer‐related death worldwide. Dysregulated RNA splicing factors have been reported to be associated with tumorigenesis ...and development in colon cancer. In this study, we interrogated clinical and RNA expression data of colon cancer patients from The Cancer Genome Atlas (TCGA) dataset and the Gene Expression Omnibus (GEO) database. Genes regulating RNA splicing correlated with survival in colon cancer were identified and a risk score model was constructed using Cox regression analyses. In the risk model, RNA splicing factor peroxisome proliferator‐activated receptor‐γ coactivator‐1α (PPARGC1) is correlated with a good survival outcome, whereas Cdc2‐like kinase 1(CLK1), CLK2, and A‐kinase anchor protein 8‐like (AKAP8L) with a bad survival outcome. The risk model has a good performance for clinical prognostic prediction both in the TCGA cohort and the other two validation cohorts. In the tumor microenvironment (TME) analysis, the immune score was higher in the low‐risk group, and TME‐related pathway gene expression was also higher in low‐risk group. We further verified the mRNA and protein expression levels of these four genes in the adjacent nontumor, tumor, and liver metastasis tissues of colon cancer patients, which were consistent with bioinformatics analysis. In addition, knockdown of AKAP8L can suppress the proliferation and migration of colon cancer cells. Animal studies have also shown that AKAP8L knockdown can inhibit tumor growth in colon cancer in vivo. We established a prognostic risk model for colon cancer based on genes related to RNA splicing regulation and uncovered the role of AKAP8L in promoting colon cancer progression.
we interrogated transcriptome and the corresponding clinical data of colon cancer patients from the The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset to investigate prognosis associated splicing‐related signature.And our study established a prognostic risk model based on RNA splicing regulation related genes for colon cancer.
A two-marker combination of plastid rbcL and matK has previously been recommended as the core plant barcode, to be supplemented with additional markers such as plastid trnH–psbA and nuclear ribosomal ...internal transcribed spacer (ITS). To assess the effectiveness and universality of these barcode markers in seed plants, we sampled 6,286 individuals representing 1,757 species in 141 genera of 75 families (42 orders) by using four different methods of data analysis. These analyses indicate that (i) the three plastid markers showed high levels of universality (87.1–92.7%), whereas ITS performed relatively well (79%) in angiosperms but not so well in gymnosperms; (ii) in taxonomic groups for which direct sequencing of the marker is possible, ITS showed the highest discriminatory power of the four markers, and a combination of ITS and any plastid DNA marker was able to discriminate 69.9–79.1% of species, compared with only 49.7% with rbcL + matK; and (iii) where multiple individuals of a single species were tested, ascriptions based on ITS and plastid DNA barcodes were incongruent in some samples for 45.2% of the sampled genera (for genera with more than one species sampled). This finding highlights the importance of both sampling multiple individuals and using markers with different modes of inheritance. In cases where it is difficult to amplify and directly sequence ITS in its entirety, just using ITS2 is a useful backup because it is easier to amplify and sequence this subset of the marker. We therefore propose that ITS/ITS2 should be incorporated into the core barcode for seed plants.
Cymbidium is an orchid genus that has undergone rapid radiation and has high ornamental, economic, ecological and cultural importance, but its classification based on morphology is controversial. The ...plastid genome (plastome), as an extension of plant standard DNA barcodes, has been widely used as a potential molecular marker for identifying recently diverged species or complicated plant groups. In this study, we newly generated 237 plastomes of 50 species (at least two individuals per species) by genome skimming, covering 71.4% of members of the genus Cymbidium. Sequence‐based analyses (barcoding gaps and automatic barcode gap discovery) and tree‐based analyses (maximum likelihood, Bayesian inference and multirate Poisson tree processes model) were conducted for species identification of Cymbidium. Our work provides a comprehensive DNA barcode reference library for Cymbidium species identification. The results show that compared with standard DNA barcodes (rbcL + matK) as well as the plastid trnH‐psbA, the species identification rate of the plastome increased moderately from 58% to 68%. At the same time, we propose an optimized identification strategy for Cymbidium species. The plastome cannot completely resolve the species identification of Cymbidium, the main reasons being incomplete lineage sorting, artificial cultivation, natural hybridization and chloroplast capture. To further explore the potential use of nuclear data in identifying species, the Skmer method was adopted and the identification rate increased to 72%. It appears that nuclear genome data have a vital role in species identification and are expected to be used as next‐generation nuclear barcodes.
Advanced nasopharyngeal carcinoma (NPC) has a poor prognosis, with an unfavorable response to palliative chemotherapy. Unfortunately, there are few effective therapeutic regimens. Therefore, we ...require novel treatment strategies with enhanced efficacy. The present study aimed to investigate the antitumor efficacy of APG-1252-M1, a dual inhibitor of BCL-2/BCL-XL, as a single agent and combined with gemcitabine. We applied various apoptotic assays and used subcutaneous transplanted NPC model to assess the in vitro and in vivo antitumor activity. Moreover, phospho-tyrosine kinase array was used to investigate the combined therapy's potential synergistic mechanism. In addition, further validation was performed using immunohistochemistry and western blotting. In vitro, we observed that APG-1252-M1 had moderate antitumor activity toward NPC cells; however, it markedly improved gemcitabine's ability to promote NPC cell apoptosis and suppress invasion, migration, and proliferation. Specifically, APG-1252 plus gemcitabine exhibited even remarkable antitumor activity in vivo. Mechanistically, the drug combination synergistically suppressed NPC by activating caspase-dependent pathways, blocking the phospho (p)-JAK-2/STAT3/MCL-1 signaling pathway, and inhibiting epithelial-mesenchymal transition. In conclusion, the results indicated that the combination of APG-1252 and gemcitabine has synergistic anticancer activities against NPC, providing a promising treatment modality for patients with NPC.
The relationship between physical activity and hyperuricemia (HUA) remains inconsistent, and the dose-response association between moderate-to- vigorous physical activity (MVPA) level and HUA still ...unclear. In this study, we aimed to investigate the dose-response association of MVPA with HUA, and to explore an appropriate range of MVPA level for preventing HUA.
Data from the US National Health and Nutrition Examination Survey (NHANES) 2007-2018 were used, including 28740 non-gout adult Americans. MVPA level was self-reported using the Global Physical Activity Questionnaire and serum uric acid was measured using timed endpoint method. The dose-response relationship between MVPA level and HUA was modeled with restricted cubic spline analysis. Logistic regression analysis were applied to estimate odd ratios (ORs) and 95% confidence intervals (CIs) of the relationships between MVPA level and HUA.
A total of 28740 adults were included in the study (weighted mean age, 47.3 years; 46.5% men), with a prevalence rate of HUA was 17.6%. The restricted cubic spline functions depicted a general U-shaped relationship between MVPA level and HUA. The MVPA level of 933 and 3423 metabolic equivalent (MET) -min/wk were the cut-off discriminating for the risk of HUA. Participants with MVPA levels in the range of 933-3423 MET-min/wk had lower risk of HUA and they had the lowest risk when MVPA levels at around 1556 MET-min/wk. Compared with the moderate-activity group (600-2999 Met-min/wk), the low-activity group (< 600 Met-min/wk) had a greater risk of HUA (OR, 1.13 95%CI, 1.02-1.26) after fully adjusting for potential confounders.
Compared with the moderate MVPA level, the low MVPA level was associated with the higher risk of HUA. And there may be a U-shaped dose-response relationship between MVPA level and HUA. When MVPA level was approximately 933-3423 MET-min/wk, the risk of HUA may at a lower level and the risk reached the lowest when MVPA level at around 1556 MET-min/wk.
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