Spatiotemporal distribution, light absorption characteristics, and source apportionments of black and brown carbon in China.

Black carbon (BC) and brown carbon (BrC) are aerosols that absorb light and thereby contribute to climate change. In this study, the light absorption properties and spatiotemporal distributions of equivalent BC (eBC) and BrC aerosols were determined based on continuous measurements of aerosol light absorption from January to August 2017, using a seven-channel aethalometer at 49 sampling sites in China. The source apportionments of BC and BrC were identified using the BC/PM2.5, absorption Ångström exponent, the concentration-weighted trajectory method, and the random forest model. Based on the results, BC was the dominant light absorber, whereas BrC was responsible for a higher proportion of the light absorption in northern compared to southern China. The light absorption of BrC was highest in winter (34.3 Mm-1), followed by spring (19.0 Mm-1) and summer (3.6 Mm-1). The combustion of liquid fuels accounted for over 50 % of the light absorption coefficient of BC in most cities and the importance of carbon monoxide (CO) and nitrogen dioxide (NO2) was over 10 % for BC emitted by liquid fuel combustion, based on the random forest model. The contribution of solid fuel combustion to BC in the north was larger than that in the southern regions as coal combustion and crop residue burning are important emission sources of BC in most northern cities. The contribution of primary BrC to light absorption was high in some northern cities, whereas that of secondary BrC was prevalent in some southern cities. The diurnal variations in secondary BrC were affected by changes in odd oxygen and relative humidity, which promoted the photobleaching of the chromophores and aqueous-phase reactions of secondary BrC.

Identification and validation of LINC01322 as a potential prognostic biomarker and oncogene promoting tumor progression in lung adenocarcinoma.

Our study identified a novel long noncoding RNA, LINC01322, that acts as an oncogene in lung adenocarcinoma progression. Cytoplasmic and nuclear RNA purification assays indicated that LINC01322 was localized in the cytoplasm and nucleus. Gene set enrichment analysis revealed the involvement of LINC01322 in the regulation of cell proliferation, migration, and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. LINC01322 may promote lung adenocarcinoma proliferation and migration through the Janus kinase/signal transducer and activator of transcription signaling pathway. In vitro experiments demonstrated that the knockdown of LINC01322 significantly suppressed lung adenocarcinoma cell proliferation, migration, and activation of the Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway, whereas overexpression had the opposite effects. Inhibition of the Janus kinase 2/signal transducer and activator of transcription 3 pathway activity partially reversed the enhancement of cell proliferation and migration caused by LINC01322 overexpression. In vivo experiments further verified the oncogene role of LINC01322. Altogether, our findings suggest that LINC01322 promotes lung adenocarcinoma progression by activating the Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway and that it could be a therapeutic target.

DHX38 enhances proliferation, metastasis, and EMT progression in NSCLC through the G3BP1-mediated MAPK pathway.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a prevalent and aggressive malignancy with limited therapeutic options. Despite advances in treatment, NSCLC remains a major cause of cancer-related death worldwide. Tumor heterogeneity and therapy resistance present challenges in achieving remission. Research is needed to provide molecular insights, identify new targets, and develop personalized therapies to improve outcomes. METHODS: The protein expression level and prognostic value of DHX38 in NSCLC were explored in public databases and NSCLC tissue microarrays. DHX38 knockdown and overexpression cell lines were established to evaluate the role of DHX38 in NSCLC. In vitro and in vivo functional experiments were conducted to assess proliferation and metastasis. To determine the underlying molecular mechanism of DHX38 in human NSCLC, proteins that interact with DHX38 were isolated by IP and identified by LC-MS. KEGG analysis of DHX38-interacting proteins revealed the molecular pathway of DHX38 in human NSCLC. Abnormal pathway activation was verified by Western blot analysis and immunohistochemical (IHC) staining. A molecule-specific inhibitor was further used to explore potential therapeutic targets for NSCLC. The pathway-related target that interacted with DHX38 was verified by co-immunoprecipitation(co-IP) experiments. In cell lines with stable DHX38 overexpression, the target protein was knocked down to explore its complementary effect on DHX38 overexpression-induced tumor promotion. RESULTS: The protein expression of DHX38 was increased in NSCLC, and patients with high DHX38 expression levels had a poor prognosis. In vitro and in vivo experiments showed that DHX38 promoted the proliferation, migration and invasion of human NSCLC cells. DHX38 overexpression caused abnormal activation of the MAPK pathway and promoted epithelial-mesenchymal transition (EMT) in tumours. SCH772984, a novel specific ERK1/2 inhibitor, significantly reduced the increases in cell proliferation, migration and invasion caused by DHX38 overexpression. The co-IP experiments confirmed that DHX38 interacted with the Ras GTPase-activating protein-binding protein G3BP1. DHX38 regulated the expression of G3BP1. Knocking down G3BP1 in cells with stable DHX38 overexpression prevented DHX38-induced tumor cell proliferation, migration and invasion. Silencing G3BP1 reversed the MAPK pathway activation and EMT induced by DHX38 overexpression. CONCLUSION: In NSCLC, DHX38 functions as a tumor promoter. DHX38 modulates G3BP1 expression, leading to the activation of the MAPK signaling pathway, thus promoting tumor cell proliferation, metastasis, and the progression of epithelial-mesenchymal transition (EMT) in non-small cell lung cancer.

Integrative Analysis of Single-Cell and Bulk RNA Sequencing Reveals Prognostic Characteristics of Macrophage Polarization-Related Genes in Lung Adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is a group of cancers with poor prognosis. The combination of single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (RNA-seq) can identify important genes involved in cancer development and progression from a broader perspective. Methods: The scRNA-seq data and bulk RNA-seq data of LUAD were downloaded from the Gene Expression Omnibus (GEO) database and the Cancer Genome Atlas (TCGA) database. Analyzing scRNA-seq for core cells in the GSE131907 dataset, and the uniform manifold approximation and projection (UMAP) was used for dimensionality reduction and cluster identification. Macrophage polarization-associated subtypes were acquired from the TCGA-LUAD dataset after analysis, followed by further identification of differentially expressed genes (DEGs) in the TCGA-LUAD dataset (normal/LUAD tissue samples, two subtypes). Venn diagrams were utilized to visualize differentially expressed and highly variable macrophage polarization-related genes. Subsequently, a prognostic risk model for LUAD patients was constructed by univariate Cox and Least Absolute Shrinkage and Selection Operator (LASSO), and the model was investigated for stability in the external data GSE72094. After analyzing the correlation between the trait genes and significantly mutated genes, the immune infiltration between the high/low-risk groups was then examined. The Monocle package was applied to analyze the pseudo-temporal trajectory analysis of different cell clusters in macrophage clusters. Subsequently, cell clusters of data macrophages were selected as key cell clusters to explore the role of characteristic genes in different cell populations and to identify transcription factors (TFs) that affect signature genes. Finally, qPCR were employed to validate the expression levels of prognosis signature genes in LUAD. Results: 424 macrophage highly variable genes, 3920 DEGs, and 9561 DEGs were obtained from macrophage clusters, the macrophage polarization-related subtypes, and normal/LUAD tissue samples, respectively. Twenty-eight differentially expressed and highly mutated MPRGs were obtained. A prognostic risk model with 7 DE-MPRGs (RGS13, ADRB2, DDIT4, MS4A2, ALDH2, CTSH, and PKM) was constructed. This prognostic model still has a good prediction effect in the GSE72094 dataset. ZNF536 and DNAH9 were mutated in the low-risk group, while COL11A1 was mutated in the high-risk group, and they were highly correlated with the characteristic genes. A total of 11 immune cells were significantly different in the high/low-risk groups. Five cell types were again identified in the macrophage cluster, and then NK cells: CD56hiCD62L+ differentiated earlier and were present mainly on 2 branches. While macrophages were present on 2 branches and differentiated later. It was found that the expression levels of BCLAF1 and MAX were higher in cluster 1, which might be the TFs affecting the expression of the characteristic genes. Moreover, qPCR confirmed that the expression of the prognosis genes was generally consistent with the results of the bioinformatic analysis. Conclusion: Seven MPRGs (RGS13, ADRB2, DDIT4, MS4A2, ALDH2, CTSH, and PKM) were identified as prognostic genes for LUAD and revealed the mechanisms of MPRGs at the single-cell level.

Design and evaluation of α-helix-based peptide inhibitors for blocking PD-1/PD-L1 interaction.

The current research in tumor immunotherapy indicates that blocking the protein-protein interaction (PPI) between PD-1 and its ligand, PD-L1, may be one of the most effective treatments for cancer patients. The α-helix is a common elements of protein secondary structure and is often involved in protein interaction. Thus, α-helix-based peptides could mimic proteins involved in such interactions and are also capable of modulating PPI in vivo. In this study, starting from a potential α-helix-rich protein, we designed a series of α-helix-based peptide candidates to block PD-1/PD-L1 interaction. These candidates were first screened using molecular docking and molecular dynamics simulations, and then their capacities to inhibit PD-1/PD-L1 interactions and to restore antitumor immune activities were investigated using the HTRF assay, SPR assay, cellular co-culture experiments and animal model experiments. Two peptides exhibited the best anti-tumor effects and the strong ability to restore the immunity of tumor-infiltrating T-cells. Further D-amino acid substitution was employed to improve the serum stability of peptide candidate, making the intravenous administration easier while maintaining the therapeutic efficacy. The resultant peptides showed promise as checkpoint inhibitors for application in tumor immunotherapy. These findings suggested that our strategy for developing peptides starting from an α-helical structure could be used in the design of bioactive inhibitors to potential block protein-protein interactions.

Validation and calibration of aerosol optical depth and classification of aerosol types based on multi-source data over China.

A refined classification of aerosol types is essential to identify and control air pollution sources. This study focused on improving the resolution and accuracy of aerosol optical depth (AOD) and further refining the classification of aerosol types in China. We validated the accuracy of the AOD acquired using the Modern-Era Retrospective Analysis for Research and Applications version 2 (MERRA2) and Copernicus Atmosphere Monitoring Service (CAMS) by comparing it with that acquired using from the Aeronet Robotic Network (AERONET). We simulated the AOD with high spatial resolution and accuracy based on the extremely randomized trees (ERT), adaptive boosting (AdaBoost), and gradient boosting decision trees (GBDT) models and identified aerosol types based on the Angstrom Exponent (AE) from the Moderate Resolution Imaging Spectroradiometer (MODIS) and the calibrated AOD. The results showed that CAMS overestimates AOD (21.4 %) and MERRA2 underestimates AOD (-17.3 %). Among the three machine learning models, the ERT model performed best, with a determination coefficient (R2) of 0.825 and the root-mean-square error (RMSE) of 0.174. Biomass burning/urban-industrial aerosols dominated China, with the largest contributions to southern, eastern, and central China in spring and summer. Clean continental aerosols contributed the most to southwestern China in fall and winter, whereas desert dust aerosols contributed the most to northwestern and eastern China in spring.

Identification of Potential RBPJ-Specific Inhibitors for Blocking Notch Signaling in Breast Cancer Using a Drug Repurposing Strategy.

Notch signaling is a key parameter in regulating cell fate during tissue homeostasis, and an aberrant Notch pathway can result in mammary gland carcinoma and has been associated with poor breast cancer diagnosis. Although inhibiting Notch signaling would be advantageous in the treatment of breast cancer, the currently available Notch inhibitors have a variety of side effects and their clinical trials have been discontinued. Thus, in search of a more effective and safer Notch inhibitor, inhibiting recombinant signal binding protein for immunoglobin kappaJ region (RBPJ) specifically makes sense, as RBPJ forms a transcriptional complex that activates Notch signaling. From our established database of more than 10,527 compounds, a drug repurposing strategy-combined docking study and molecular dynamic simulation were used to identify novel RBPJ-specific inhibitors. The compounds with the best performance were examined using an in vitro cellular assay and an in vivo anticancer investigation. Finally, an FDA-approved antibiotic, fidaxomicin, was identified as a potential RBPJ inhibitor, and its ability to block RBPJ-dependent transcription and thereby inhibit breast cancer growth was experimentally verified. Our study demonstrated that fidaxomicin suppressed Notch signaling and may be repurposed for the treatment of breast cancer.

Long noncoding RNA LMO7DN inhibits cell proliferation by regulating the cell cycle in lung adenocarcinoma.

In our previous study, we reported that the long noncoding RNA, LMO7 downstream neighbor (LMO7DN), has a strong prognostic value in lung adenocarcinoma (LUAD). In this study, we further investigated the role of LMO7DN in LUAD progression. LMO7DN was found to be expressed at low levels in LUAD tissues, and its high expression predicted good prognosis. Bioinformatics analysis indicated that LMO7DN was closely associated with the cell cycle. Furthermore, we found that cell proliferation was significantly enhanced following knockdown of LMO7DN, and the number of cells in the G2/M phase was markedly decreased, whereas there was no change in apoptosis. Thus, LMO7DN inhibits cell proliferation by affecting the cell cycle and is of significant prognostic value in LUAD.

Association Between Neutrophil-Lymphocyte Ratio and All-Cause Mortality and Cause-Specific Mortality in US Adults, 1999-2014.

BACKGROUND: Neutrophil-lymphocyte ratio (NLR) is a novel marker of inflammation. Emerging studies have evaluated the relationship of NLR with cardiovascular diseases and malignant conditions. However, rare studies regarded the association between NLR and long-term health status. This study aimed to evaluate the association of NLR with all-cause mortality and cause-specific mortality among adults in the United States. METHODS: We obtained eight cycles data of National Health and Nutrition Examination Surveys (NHANES) from 1999 to 2014, and enrolled 32328 participants after certain screening. By weighted chi-square test and linear regression analysis, we analyzed the correlation between NLR and baseline characteristics of the participants. Kaplan-Meier curves and Cox regression models were used to assess the survival relevance of NLR. We conducted stratified analysis, interaction analysis, and sensitivity analysis to robustness of our results. RESULTS: Participants with high NLR levels had a higher risk of death. After adjustment for baseline characteristics, the hazard ratio comparing the higher vs lower NLR levels was 1.43 (95% CI, 1.18-1.73) for all-cause mortality, 1.27 (95% CI, 0.84-1.92) for cancer mortality, and 1.44 (95% CI, 0.96-2.16) for cardiovascular disease mortality. Stratified analysis found that the observed associations between NLR levels and mortality did not differ significantly. CONCLUSION: In this nationally representative cohort of US adults, higher NLR was significantly associated with an increased risk of all-cause mortality.

Comparison of submental tumorigenesis model and axillary tumorigenesis model in nude mice xenotransplanted with human hypopharyngeal carcinoma cells / 第二军医大学学报

Objective To establish a submental tumorigenesis model by injecting human hypopharyngeal carcinoma cells to nude mice, and to compare the model with traditional axillary tumorigenesis model. Methods Five-week-old male nude mice were selected and divided into submental tumorigenesis model group (submental group) and axillary tumorigenesis model group (axillary group). Each group was divided into two subgroups by injecting human hypopharyngeal carcinoma cells FADU or HN31, namely sub-FADU, sub-HN31, ax-FADU, and ax-HN31 groups, with 12 nude mice in each group. The nude mice in the submental group were injected with tumor cells in the left side of submental area, and those in the axillary group were injected with tumor cells in the right side of axillary area. The time of tumor formation, tumor volume and body mass of nude mice were measured. The death of nude mice was recorded. After eight weeks, the local tumor growth, infiltration, and organ metastasis such as liver, spleen and kidney of the survival nude mice were examined by ultrasound, and the tumor metastasis was observed by routine H-E staining and immunohistochemical staining. Results On the 7th and 9th days after injection, the tumors were observed in the submental group and the axillary group. On the 33rd day after injection, the tumor volume in the ax-FADU and ax-HN31 groups was significantly bigger than those in the sub-FADU and sub-HN31 groups (P<0.05, P<0.01). The body mass of nude mice in each group reached peak on the 17th to 19th days after injection, and thereafter the body mass in the submental group was gradually decreased and that in the axillary group was still increased. On the 33rd day after injection, the body mass in the ax-FADU and ax-HN31 groups were significantly higher than those in the sub-FADU and sub-HN31 groups, respectively (P<0.01). After eight weeks, there were eight deaths in the sub-FADU group and 10 in the sub-HN31 group, with six mice alive in the submental group; there were six deaths in the ax-FADU group and six in the ax-HN31 group, with 12 alive in the axillary group. There was no significant difference in mortality of nude mice between the four subgroups. Ultrasound and pathological examination showed that four survived nude mice were found with cervical lymph node and liver metastases in the submental group, and only one was found with liver metastases in the axillary group; and the difference between the two groups was statistically significant (P<0.05). There were two pulmonary metastases in the submental group, and one in the axillary group; there was one spleen metastases in the submental group and no spleen metastases in the submental group; and there were no significant differences between the two groups. Conclusion Submental tumorigenesis model and axillary tumorigenesis model have their own characteristics. The submental tumorigenesis model has shorter tumorigenesis time, higher local invasion and higher distant metastasis rate, and is suitable for studying the invasiveness and metastasis of tumor in vivo. The axillary tumorigenesis model has larger volume of tumor, less injury to the adjacent organs and tissues, longer survival time and lower distant metastasis rate, and is suitable for the study of the characteristics of tumor cells.

[Extraction of total RNA and cloning of sgDHAR gene from Siraitia grosvenorii].

Total RNA was isolated from Siraitia grosvenorii fruit by the method of modified Trizol, according to S. grosvenorii fruit characteristics of rich phenols, polysaccharide, oil and proteins. The OD260/280, OD260/230, RNA integrity (RIN) and yield of the total RNA with this method were 2.01, 2.02, 9.50 and 260 mirog.g-1, respectively. The open reading frame (ORF) of dehydroascorbate reductase (DHAR), named as SgDHAR, was cloned by rapid amplification of cDNA ends (RACE) and RT-PCR method from S. grosvenorii. The GenBank accession number for this gene is KC907731. The SgDHAR gene contains a full-length cDNA of 1,252 bp including ORF of 819 bp and encodes a predicted protein of 272 amino acids. The molecular mass is 30.217 7 kD and the isoelectric point is 8.76. Homology comparison showed that it shared 87% nucleotide sequence homology with Cucumis sativus. Expression patterns using qRT-PCR analysis showed that SgDHAR was mainly expressed in fruit and stem, followed by flower, and was lowest in root, while the expression level was 6.83 times in triploid. T than that in diploid. Therefore, SgDHAR gene may be involved in abortion of triploid seedless S. grosvenorii.

Comparative vesicle proteomics reveals selective regulation of protein expression in chestnut blight fungus by a hypovirus.

The chestnut blight fungus (Cryphonectria parasitica) and hypovirus constitute a model system to study fungal pathogenesis and mycovirus-host interaction. Knowledge in this field has been gained largely from investigations at gene transcription level so far. Here we report a systematic analysis of the vesicle proteins of the host fungus with/without hypovirus infection. Thirty-three differentially expressed protein spots were identified in the purified vesicle protein samples by two-dimensional electrophoresis and mass spectrometry. Down-regulated proteins were mostly cargo proteins involved in primary metabolism and energy generation and up-regulated proteins were mostly vesicle associated proteins and ABC transporter. A virus-encoded protein p48 was found to have four forms with different molecular mass in vesicles from the virus-infected strain. While a few of the randomly selected differentially expressed proteins were in accordance with their transcription profiles, majority were not in agreement with their mRNA accumulation patterns, suggesting that an extensive post-transcriptional regulation may have occurred in the host fungus upon a hypovirus infection.

[A comparison study on the physical/chemical properties and immunomodulatory activities of mycelial polysaccharide extracts from five Ganoderma species].

Five Ganoderma species, including G. lucidum, G. tsugae, G. oerstedii, G. resinaceum and G. subamboinens, were parallel studied under an identical condition. These species were cultivated using liquid fermentation and their mycelia polysaccharides were extracted and compared on the physical/chemical properties and in vitro immunomodulatory activities. These results showed that the polysaccharide yields varied markedly among different species, and G. oerstedii was the highest among the five. However, HPLC analysis showed all the polysaccharide extracts had similar molecular weight distributions and monosaccharide compositions. They all contained glucose, galactose, mannose, glucosamine hydrochloride and fucose. In vitro assays, these polysaccharide extracts significantly stimulated phagocytosis and nitric oxide production by RAW 264.7 macrophage cell line, and G. subamboinens exerted the strongest potency. When Con A was not or presented, they all showed an up-or-down immunomodulatory effect on mouse splenocyte proliferation. The results illustrate that in addition to G. lucidum and G. tsugae, which are the two mostly studied and applied species, other Ganoderma species can also produce polysaccharides with similar physical/chemical properties and with similar immunomodulatory activities.