Urinary volatile organic compound metabolites and COPD among US adults: mixture, interaction and mediation analysis.

BACKGROUND: Volatile organic compounds (VOCs) encompass hundreds of high production volume chemicals and have been reported to be associated with adverse respiratory outcomes such as chronic obstructive pulmonary disease (COPD). However, research on the combined toxic effects of exposure to various VOCs on COPD is lacking. We aimed to assess the effect of VOC metabolite mixture on COPD risk in a large population sample. METHODS: We assessed the effect of VOC metabolite mixture on COPD risk in 5997 adults from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2020 (pre-pandemic) using multivariate logistic regression, Bayesian weighted quantile sum regression (BWQS), quantile-based g-Computation method (Qgcomp), and Bayesian kernel machine regression (BKMR). We explored whether these associations were mediated by white blood cell (WBC) count and total bilirubin. RESULTS: In the logistic regression model, we observed a significantly increased risk of COPD associated with 9 VOC metabolites. Conversely, N-acetyl-S-(benzyl)-L-cysteine (BMA) and N-acetyl-S-(n-propyl)-L-cysteine (BPMA) showed insignificant negative correlations with COPD risk. The overall mixture exposure demonstrated a significant positive relationship with COPD in both the BWQS model (adjusted odds ratio (OR) = 1.30, 95% confidence interval (CI): 1.06, 1.58) and BKMR model, and with marginal significance in the Qgcomp model (adjusted OR = 1.22, 95% CI: 0.98, 1.52). All three models indicated a significant effect of the VOC metabolite mixture on COPD in non-current smokers. WBC count mediated 7.1% of the VOC mixture associated-COPD in non-current smokers. CONCLUSIONS: Our findings provide novel evidence suggesting that VOCs may have adverse associations with COPD in the general population, with N, N- Dimethylformamide and 1,3-Butadiene contributing most. These findings underscore the significance of understanding the potential health risks associated with VOC mixture and emphasize the need for targeted interventions to mitigate the adverse effects on COPD risk.

Wilms' tumour gene 1 (WT1) enhances non-small cell lung cancer malignancy and is inhibited by microRNA-498-5p.

BACKGROUND: Wilms' tumour gene 1 (WT1) is clearly recognized as a tumour promoter in diversiform of human malignancies. Nevertheless, knowledge of its expression, functions and potential molecular mechanisms in non-small cell lung cancer (NSCLC) remains elusive. METHODS: Differential expression of WT1 mRNA and protein between NSCLC and normal tissues were assessed by analyzing RNA-seq data from Oncomine and protein data from Human Protein Atlas, respectively. Subsequently, prognosis significance and immune cell infiltration were analyzed by Kaplan-Meier plotter and CIBERSORT. 60 pairs of local NSCLC tissues were involved to validate WT1 expression by quantitative PCR (qPCR) and Western blot. Moreover, Cell Counting Kit-8 (CCK-8), colony formation, transwell, dual luciferase reporter assays and in vivo xenograft tumour growth experiments were conducted to explore the function and mechanism of WT1 in NSCLC. RESULTS: Our solid data indicated that WT1 was increased in NSCLC tissues and cell lines in comparison with their matched controls. In particular, its upregulation correlated with worse prognosis and immune infiltration of the patients. Functional assays demonstrated that knockdown of WT1 inhibited NSCLC malignancy, including inhibiting cell proliferation, survival and invasion. Further exploration discovered that microRNA-498-5p (miR-498-5p) was the upstream suppressor of WT1 by directly targeting the 3' untranslated region (UTR) of WT1 mRNA. Moreover, expression of miR-498-5p was notably decreased and inversely correlated with WT1 in NSCLC tissues. Finally, we proved that miR-498-5p was a potent tumour suppressor in NSCLC by suppressing cell proliferation, survival and invasion, while WT1 restoration could in turn disrupt this suppression both in vitro and in vivo. CONCLUSION: The abnormal increase in WT1 contributes to the malignant properties of NSCLC cells, and miR-498-5p is a natural inhibitor of WT1. Our findings might facilitate the development of novel therapeutic strategies against NSCLC in the future.

Single-Cell Transcriptomics Unveils the Dedifferentiation Mechanism of Lung Adenocarcinoma Stem Cells.

Lung adenocarcinoma (LUAD) is a major subtype of lung cancer, and its prognosis is still poor due to therapy resistance, metastasis, and recurrence. In recent years, increasing evidence has shown that the existence of lung cancer stem cells is responsible for the propagation, metastasis, therapy resistance, and recurrence of the tumor. During their transition to cancer stem cells, tumor cells need to inhibit cell differentiation and acquire invasive characteristics. However, our understanding of the property and role of such lung cancer stem cells is still limited. In this study, lung adenocarcinoma cancer stem cells (LCSCs) were enriched from the PC-9 cell line in a serum-free condition. PC-9 cells grew into spheres and showed higher survival rates when exposed to gefitinib: the drug used for the treatment of LUAD. Additionally, we found that the canonical stemness marker protein CD44 was significantly increased in the enriched LCSCs. Then, LCSCs were inoculated into the groin of nude mice for 1.5 months, and tumors were detected in the animals, indicating the strong stemness of the cells. After that, we performed single-cell RNA sequencing (scRNA-seq) on 7320 LCSCs and explored the changes in their transcriptomic signatures. We identified cell populations with a heterogeneous expression of cancer stem marker genes in LCSCs and subsets with different degrees of differentiation. Further analyses revealed that the activation of the FOXM1 (oncoprotein) transcription factor is a key factor in cell dedifferentiation, which enables tumor cells to acquire an epithelial-mesenchymal transition phenotype and increases the LCSC surface marker CD44. Moreover, we found that the combination of CD44, ABCG2, and ALCAM was a specific marker for LCSCs. In summary, this study identified the potential factors and molecular mechanisms underlying the stemness properties of LUAD cancer cells; it could also provide insight into developing novel and effective therapeutic approaches.

Hsa_circ_001659 serves as a novel diagnostic and prognostic biomarker for colorectal cancer.

Colorectal cancer (CRC) is prevalent worldwide and novel diagnostic and prognostic biomarkers are needed to improve precision medicine. Circular RNAs (circRNAs) are currently being considered as emerging tumor biomarkers. Herein, we aimed to explore the possible clinical application of circRNAs in the early diagnosis and prognostic prediction of CRC. First, candidate circRNA was selected by integrating analysis of Gene Expression Omnibus (GEO) database using GEO2R program. ROC curve analysis demonstrated the predictive values and likelihood ratios of circ_001659 were satisfactory for the diagnosis of CRC, including patients in early-stage disease or patients with carcinoembryonic antigen (CEA)-negative status. Moreover, serum circ_001659 may be a novel biomarker in the assessment of successful treatment and remission of cancer tracking. We further investigated the oncogenic role of circ_001659. In vivo and in vitro experiments indicated that circ_001659 could promote CRC cell invasion and migration. Mechanistically, circ_001659 was localized in the nucleus, recruited the RBBP5 to Vimentin promoter and increased H3K4 trimethylation level on the Vimentin promoter region, which epigenetically activated Vimentin transcription. Our findings demonstrate that circ_001659 could be a useful serum biomarker for CRC diagnosis and prognosis. Targeting circ_001659 and its pathway may be meaningful for treating patients with CRC.

MicroRNA-1915-3p inhibits cell migration and invasion by targeting SET in non-small-cell lung cancer.

BACKGROUND: MicroRNAs (miRNAs) have been reported to play significant roles in non-small-cell lung cancer (NSCLC). However, the roles of microRNA (miR)-1915-3p in NSCLC remain unclear. In this study, we aimed to explore the biological functions of miR-1915-3p in NSCLC. METHODS: The expression of miR-1915-3p and SET nuclear proto-oncogene (SET) in NSCLC tissues were examined by quantitative real-time PCR (qRT-PCR). Migratory and invasive abilities of lung cancer were tested by wound healing and transwell invasion assay. The direct target genes of miR-1915-3p were measured by dual-luciferase reporter assay and western blot. Finally, the regulation between METTL3/YTHDF2/KLF4 axis and miR-1915-3p were evaluated by qRT-PCR, promoter reporter assay and chromatin immunoprecipitation (CHIP). RESULTS: miR-1915-3p was downregulated in NSCLC tissues and cell lines, and inversely associated with clinical TNM stage and overall survival. Functional assays showed that miR-1915-3p significantly suppressed migration, invasion and epithelial-mesenchymal transition (EMT) in NSCLC cells. Furthermore, miR-1915-3p directly bound to the 3'untranslated region (3'UTR) of SET and modulated the expression of SET. SET inhibition could recapitulate the inhibitory effects on cell migration, invasion and EMT of miR-1915-3p, and restoration of SET expression could abrogate these effects induced by miR-1915-3p through JNK/Jun and NF-κB signaling pathways. What's more, miR-1915-3p expression was regulated by METTL3/YTHDF2 m6A axis through transcription factor KLF4. CONCLUSIONS: These findings demonstrate that miR-1915-3p function as a tumor suppressor by targeting SET and may have an anti-metastatic therapeutic potential for lung cancer treatment.

CircKIF2A contributes to cell proliferation, migration, invasion and glycolysis in human neuroblastoma by regulating miR-129-5p/PLK4 axis.

Multiple circular RNAs (circRNAs) have been identified to act as essential mediators in diverse human cancers. However, the roles of circRNAs in neuroblastoma (NB) are largely unknown. In this study, we aimed to explore the function of circKIF2A in NB. Quantitative real-time polymerase chain reaction was executed to detect the levels of circKIF2A, KIF2A mRNA, miR-129-5p and polo-like kinase 4 (PLK4) mRNA. Actinomycin D assay and RNase R digestion assay were conducted to analyze the feature of circKIF2A. 3-(4, 5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, transwell assay and specific kits were utilized to evaluate cell proliferation, metastasis and glycolysis, respectively. Western blot assay was performed to examine the protein levels of matrix metalloproteinase 2 (MMP2), MMP9 and PLK4. Bioinformatics analysis, RNA pull-down assay and dual-luciferase reporter assay were conducted to analyze the relationship between miR-129-5p and circKIF2A or PLK4. Murine xenograft model assay was done to investigate the role of circKIF2A in NB in vivo. CircKIF2A level was increased in NB tissue samples and cell lines. Silencing of circKIF2A impeded NB cell proliferation, migration, invasion and glycolysis. For mechanism analysis, circKIF2A could positively modulate PLK4 expression via sponging miR-129-5p. Moreover, miR-129-5p inhibition reversed the inhibitory effects of circKIF2A silencing on the behaviors of NB cells. MiR-129-5p overexpression weakened the malignant biological behaviors of NB cells by targeting PLK4. Additionally, circKIF2A knockdown hampered tumorigenesis in vivo. CircKIF2A knockdown suppressed cell proliferation, migration, invasion and glycolysis via downregulating PLK4 expression through miR-129-5p.

Dynamic contrast-enhanced magnetic resonance imaging for monitoring the anti-angiogenesis efficacy in a C6 glioma rat model.

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is useful in predicting responses to angiogenic therapy of malignant tumors. PURPOSE: To observe the dynamics of DCE-MRI parameters in evaluating early effects of antiangiogenic therapy in a C6 glioma rat model. MATERIAL AND METHODS: The Bevacizumab or vehicle treatment was started from the 14th day after glioma model was established. The treated and control groups (n = 13 per group) underwent DCE-MRI scans on days 0, 1, 3, 5, and 7 after treatment. Tumor volume was calculated according to T2-weighted images. Hematoxylin and eosin, microvessel density (MVD), and proliferating cell nuclear antigen (PCNA) examination were performed on day 7. The MRI parameters between the two groups were compared and correlations with immunohistochemical scores were analyzed. RESULTS: The average tumor volume of treated group was significantly lower than that of control group on day 7 (81.764 ± 1.043 vs. 103.634 ± 3.868 mm3, P = 0.002). Ktrans and Kep decreased in the treated group while they increased in the control group. The differences were observed on day 5 (Ktrans: 0.045 ± 0.018 vs. 0.093 ± 0.014 min-1, P < 0.001; Kep: 0.062 ± 0.018 vs. 0.134 ± 0.047 min-1, P = 0.005) and day 7 (Ktrans: 0.032 ± 0.010 vs. 0.115 ± 0.025 min-1, P < 0.001; Kep: 0.045 ± 0.016 vs. 0.144 ± 0.042 min-1, P < 0.001). The difference of Ve was observed on day 5 (0.847 ± 0.248 vs. 0.397 ± 0.151, P = 0.009) and 7 (0.920 ± 0.154 vs. 0.364 ± 0.105, P = 0.006). Ktrans and Kep showed positive correlations with MVD and Ve showed negative correlation with PCNA. CONCLUSION: DCE-MRI can assess the changes of early effects of anti-angiogenic therapy in preclinical practice.

Exploring the antioxidant potential of nekemias species extracts on edible oils: In vitro assessment and lipid oxidation inhibition.

Synthetic antioxidants have long been used to protect edible oils from oxidation. However, concerns about their potential health risks and environmental impact have led to a growing interest in natural antioxidants. In this study, we explore the antioxidant properties of extracts from four Nekemias plant species: Nekemias grossedentata (AGR), Nekemias megalophylla (AME), Nekemias chaffanjonii (ACH), and Nekemias cantoniensis (ACA) by obtaining the values for different tests. We investigate their bioactive compound content and evaluate their antioxidant capabilities on six edible oils categorized into three lipid systems based on their fatty acid compositions: oleic acid, linoleic acid, and linolenic acid. Our findings demonstrate that AGR and AME extracts, rich in bioactive compounds, exhibit strong antioxidant activities in vitro, effectively inhibiting lipid oxidation, especially in oleic acid-rich oils like camellia oil. The antioxidant effects of these extracts are comparable to synthetic antioxidants such as TBHQ and superior to natural antioxidant Tea Polyphenols (TP). While the extracts also show antioxidant potential in linoleic and linolenic acid systems, the stability of their effects in these oils is lower than in oleic acid system. These results suggest that Nekemias species extracts have the potential to serve as natural additives for extending the shelf life of edible oils, contributing to the exploration of natural antioxidants.

IRE1α inhibitor enhances paclitaxel sensitivity of triple-negative breast cancer cells.

PURPOSE: Breast cancer is the most commonly diagnosed cancer in women, and triple-negative breast cancer (TNBC) accounts for approximately 15%-20% of all breast cancers. TNBC is highly invasive and malignant. Due to the lack of relevant receptor markers, the prognosis of TNBC is poor and the five-year survival rate is low. Paclitaxel is the first-line drug for the treatment of TNBC, which can inhibit cell mitosis. However, many patients develop drug resistance during treatment, leading to chemotherapy failure. Therefore, finding new therapeutic combinations to overcome TNBC drug resistance can provide new strategies for improving the survival rate of TNBC patients. METHODS: Cell viability assay, RT-qPCR, Colony formation assay, Western blot, and Xenogeneic transplantation methods were used to investigate roles and mechanisms of IRE1α/XBP1s pathway in the paclitaxel-resistant TNBC cells, and combined paclitaxel and IRE1α inhibitor in the treatment of TNBC was examined in vitro and in vivo. RESULTS: We found activation of UPR in paclitaxel-resistant cells, confirming that IRE1α/XBP1 promotes paclitaxel resistance in TNBC. In addition, we demonstrated that the combination of paclitaxel and IRE1α inhibitors can synergistically inhibit the proliferation of TNBC tumors both in vitro and in vivo,suggesting that IRE1α inhibitors combined with paclitaxel may be a new treatment option for TNBC. CONCLUSIONS: In this study, we demonstrated the important role of IRE1α signaling in mediating paclitaxel resistance and identified that combination therapies targeting IRE1α signaling could overcome paclitaxel resistance and enhance chemotherapy efficacy.

Identification of SRSF10 as a promising prognostic biomarker with functional significance among SRSFs for glioma.

AIMS: The serine/arginine-rich splicing factor (SRSF) protein family members are essential mediators of the alternative splicing (AS) regulatory network, which is tightly implicated in cancer progression. However, the expression, clinical correlation, immune infiltration, and prognostic value of SRSFs in gliomas remain unclear. MATERIALS AND METHODS: Glioma samples were extracted from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) datasets. Several databases, such as HPA, DAVID, UALCAN were used to comprehensively explore the roles of SRSFs. In addition, experimental validation of SRSF10 was also conducted. KEY FINDINGS: Here, we found the expression alterations of the SRSF family in glioma samples using data from the TCGA and CGGA_325 datasets. Among the 12 genes, most were found to be closely associated with glioma clinical features, which linked to poor prognosis in glioma patients. Interestingly, survival analysis identified only SRSF10 as a potential independent risk prognostic biomarker for glioma patients. Immune analysis indicated that glioma patients with high SRSF10 expression may respond well to immunotherapies targeting immune checkpoint (ICP) genes. Finally, knocking down SRSF10 reduced glioma cell viability, induced G1 cell cycle arrest, and induced the exclusion of bcl-2-associated transcription factor 1 (BCLAF1) exon 5a. SIGNIFICANCE: Overall, this study uncovers the oncogenic roles of most SRSF family members in glioma, with the exception of SRSF5, while highlighting SRSF10 as a potential novel independent prognostic biomarker for glioma.

Epidemiological and demographic drivers of lung cancer mortality from 1990 to 2019: results from the global burden of disease study 2019.

Background: Understanding the effects of demographic drivers on lung cancer mortality trends is critical for lung cancer control. We have examined the drivers of lung cancer mortality at the global, regional, and national levels. Methods: Data on lung cancer death and mortality were extracted from the Global Burden of Disease (GBD) 2019. Estimated annual percentage change (EAPC) in the age-standardized mortality rate (ASMR) for lung cancer and all-cause mortality were calculated to measure temporal trends in lung cancer from 1990 to 2019. Decomposition analysis was used to analyze the contributions of epidemiological and demographic drivers to lung cancer mortality. Results: Despite a non-significant decrease in ASMR [EAPC = -0.31, 95% confidence interval (CI): -1.1 to 0.49], the number of deaths from lung cancer increased by 91.8% [95% uncertainty interval (UI): 74.5-109.0%] between 1990 and 2019. This increase was due to the changes in the number of deaths attributable to population aging (59.6%), population growth (56.7%), and non-GBD risks (3.49%) compared with 1990 data. Conversely, the number of lung cancer deaths due to GBD risks decreased by 19.8%, mainly due to tobacco (-12.66%), occupational risks (-3.52%), and air pollution (-3.47%). More lung cancer deaths (1.83%) were observed in most regions, which were due to high fasting plasma glucose levels. The temporal trend of lung cancer ASMR and the patterns of demographic drivers varied by region and gender. Significant associations were observed between the contributions of population growth, GBD risks and non-GBD risks (negative), population aging (positive), and ASMR in 1990, the sociodemographic index (SDI), and the human development index (HDI) in 2019. Conclusion: Population aging and population growth increased global lung cancer deaths from 1990 to 2019, despite a decrease in age-specific lung cancer death rates due to GBD risks in most regions. A tailored strategy is needed to reduce the increasing burden of lung cancer due to outpacing demographic drivers of epidemiological change globally and in most regions, taking into account region- or gender-specific risk patterns.

The impact of low-dose CT on smoking behavior among non-smokers, former-smokers, and smokers: A population-based screening cohort in rural China.

BACKGROUND: Lung cancer screening may provide a "teachable moment" for the smoking cessation and relapse prevention. However, the impact of lung cancer screening on smoking initiation in non-smokers has not been reported. METHODS: A baseline smoking behavior survey was conducted in 2000 participants who were screened by low-dose computed tomography (LDCT) from 2014 to 2018. All participants were re-surveyed on their smoking behavior in 2019. Of these, 312 participants were excluded, leaving 1688 participants in the final analysis. The smoking initiation rate in baseline non-smokers, the relapse rate in baseline former smokers, and the abstinence rate in baseline current smokers were calculated, respectively. The associations between screening results, demographic characteristics, and smoking behavior change were analyzed using multivariable logistic regression. RESULTS: From 2014 to 2019, smoking prevalence significantly decreased from 52.6% to 49.1%. The prevalence of smoking initiation, relapse, and abstinence in baseline non-smokers, former, and current smokers was 16.8%, 22.9%, and 23.7%, respectively. The risk of smoking initiation in baseline non-smokers was significantly higher in those with negative screening result (adjusted OR = 2.97, 95% CI: 1.27-6.94). Compared to smokers who only received baseline screening, the chance of smoking abstinence in baseline current smokers was reduced by over 80% in those who attended 5 rounds of screening (adjusted OR = 0.15, 95% CI:0.08-0.27). No significant associations were found between smoking relapse and prior screening frequency, with at least one positive screening result. Age, gender, occupational exposure, income, and smoking pack years were also associated with smoking behavior changes. CONCLUSIONS: The overall decreased smoking prevalence indicated an overwhelming effect of "teachable moment" on "license to smoke." A tailored smoking cessation strategy should be integrated into lung cancer screening.

[Non-structural protein NS1 of canine parvovirus induces the apoptosis of cells].

OBJECTIVE: To investigate the effects of canine parvovirus (CPV) non-structural protein-1 (NS1) on the cell apoptosis induced by CPV and preliminarily explore the mechanism of CPV-induced apoptosis. METHODS: First, the NS1 gene was amplified by PCR from CPV genomic DNA and subcloned into pcDNA3. 1A vector to generate NS1 eukaryotic expression vector pcDNA-NS1. To verify whether pcDNA-NS1 vector can mediate NS1 expression in eukaryotic cells, the human embryo kideny (HEK) 293FT cells were used to transiently express the recombinant NS1. The effects of NS1 on CPV-induced apoptosis were investigated by infecting the F81 host cells with CPV and transfecting the cells with NS1 vector. The apoptosis of the cells was detected by AnnexinV/PI double staining for phosphatidylserine externalization on membrane and by luminescence method for caspase-3/7 activities. RESULTS: The results show that the sequence of NS1 gene amplified was consistent with the GenBank. The NS1 expression vector was shown to be correct and could mediate NS1 expression in eukaryotic cells. The phosphatidylserine on outside of membrane was detected and the caspase-3/7 activities were increased in both CPV-infected cells and NS1-transfected cells. These results indicate that both CPV and NS1 protein can induce the apoptosis of the cells. CONCLUSION: CPV-induced apoptosis was closely related to its non-structural protein NS1.

[Recombinant porcine lung surfactant protein A inhibits porcine reproductive and respiratory syndrome virus infection into host cells in vitro].

OBJECTIVE: To investigate the antiviral activity of porcine lung surfactant protein A (SP-A) to porcine reproductive and respiratory syndrome virus (PRRSV) in vitro. METHODS: The SP-A gene was amplified by PCR from the plasmid containing porcine SP-A gene, and subcloned into pcDNA3. 1A-CD5 vector containing the human CD5 signal peptide to generate SP-A eukaryotic expression vector pcDNA-CD5-SPA/MH. The recombinant expression vector was transfected into HEK293T cells mediated with calcium phosphate. The expressed recombinant SP-A was identified by Western blot and purified from culture medium by Ni-NTA-Agarose beads. The binding activity of SP-A with PRRSV was identified by ELISA. The antiviral activity of SP-A to PRRSV was analyzed by viral titer reduction assays on MARC-145 cells and porcine alveolar macrophages (PAM). RESULTS: The results showed that the eukaryotic expression vector of SP-A gene could mediate SP-A expression in HEK293T cells, the expressed SP-A could bind PRRSV in a dose dependent manner. The PRRSV incubated in advance with SP-A showed the lower infective activity compared with no-SP-A-incubated PRRSV on both MARC-145 cells and porcine alveolar macrophages. The SP-A-treated PRRSV titers in MARC-145 cells and PAM cells were significantly lower than that of SP-A-untreated PRRSV at 72 h post-infection. CONCLUSION: Recombinant porcine SP-A significantly inhibit the infection of PRRSV to the host cells in vitro, which indicates that recombinant SP-A possesses anti-PRRSV activity.

Rhizosphere inoculation of Nicotiana benthamiana with Trichoderma harzianum TRA1-16 in controlled environment agriculture: Effects of varying light intensities on the mutualism-parasitism interaction.

Trichoderma spp., a genus of fast-growing and highly adaptable fungi that form symbiotic relationships with plant roots, rendering them ideal for practical use in controlled environment agriculture. Herein, this paper aims to understand how the Nicotiana benthamiana with inoculation of Trichoderma harzianum strain TRA1-16 responds to light intensity variation. Pot experiments were conducted under low and high light intensities (50 and 150 µmol·m-2·s-1, respectively) and microbial treatments. Plant growth, physio-biochemical attributes, activities of antioxidant enzymes, and phytohormones regulation were investigated. The results showed that for non-inoculated plants, the reduction in light intensity inhibited plant growth, nitrogen (N) and phosphorus (P) uptake, chlorophyll a/b, and carotenoid content. Trichoderma inoculation resulted in 1.17 to 1.51 times higher concentrations of available N and P in the soil than the non-inoculated group, with higher concentrations at high light intensity. Plant height, dry weight, nutrient uptake, and antioxidant activity were significantly increased after inoculation (p<0.05). However, the growth-promoting effect was less effective under low light conditions, with lower plant height and P content in plants. We suggested that when the light was attenuated, the mutualism of the Trichoderma turned into parasitism, slowing the growth of the host plant. The application of fungal inoculation techniques for plant growth promotion required coordination with appropriate light complementation. The mechanisms of coordination and interaction were proposed to be incorporated into the biological market theory.

Changes in litter input exert divergent effects on the soil microbial community and function in stands of different densities.

Soil microbial communities influence soil biogeochemical cycling by affecting the production of extracellular enzymes and the release of carbon dioxide. Changes in litter input or stand density due to thinning can affect soil microbial communities and their function by altering soil biochemical properties. However, it is unclear how or to what extent different amounts of litter input affect soil microbial communities and their function in forest stands with different densities. Therefore, we simulated litter removal, 50 % litter reduction, normal litter input, and double litter increase under field conditions by applying different amounts of litter to soils with different stand densities in the laboratory. We then measured soil biochemical properties, microbial communities, enzyme activity, and respiration rate. Our results revealed that the responses of soil dissolved organic carbon and total nitrogen to litter input were more pronounced in the high-density forest stand with poor soil than in the low-density forest stand with nutrient-rich soil, which was mainly reflected in that the addition of litter significantly decreased the concentration of dissolved organic carbon while increasing the content of total nitrogen in the soil of the high-density forest stand. In comparison to the soil carbon component, the nitrogen component of the soil was more affected by stand density. The responses of soil fungal and bacterial communities to leaf litter treatment varied with stand density, as reflected primarily in changes in the relative abundances of Ascomycota, unclassified_K_fungi, and Proteobacteria, and changes in the relative abundances of their functional groups (ectomycorrhizal fungi, saprophytic fungi, pathogens, parasites, and bacteria involved in the nitrogen cycle). Soil fungal community responses to changes in litter input are more sensitive in the high-density forest with nutrient-poor soil than in the low-density forest stand. Furthermore, litter input inhibited the activities of soil ß-glucuronidase, N-acetyl-ß-d-glucosaminidase, and acid phosphatase more strongly in the low-density forest stand. Litter manipulation primarily affected enzymatic activity in the high-density forest stand by changing the diversity and composition of the soil fungal community. However, in the low-density forest stand, litter treatment affected soil enzyme activity, primarily through changes in soil bacterial and fungal community composition, as well as soil respiration through changes in bacterial richness (Chao 1) and community composition. We conclude that how the change in litter input impacts the soil microbial community and its function, or the magnitude of the effects, is largely dependent on soil quality. Relationships among soil variables, microbial communities, and function differ between stand densities. Our study contributes to an enhanced understanding of the impact of changes in litter input due to climate change or anthropogenic activities on soil biogeochemical cycles and can also guide rationally formulating forest management approaches to improve microbial function under climate change.

MiR-192/NKRF axis confers lung cancer cell chemoresistance to cisplatin via the NF-κB pathway.

BACKGROUND: Chemoresistance influences the therapeutic effect of cisplatin and remains a major obstacle to its clinical use. MicroRNAs are associated with drug resistance of various tumors. However, the association between microRNAs and cisplatin in lung cancer remains largely unclear. METHODS: MicroRNA expression profile was identified by microRNA microarray between the lung cancer cisplatin-sensitive cell line A549 (A549) and cisplatin-resistant cell line A549/DDP (A549/DDP) and confirmed by quantitative real-time-PCR (qRT-PCR). In vitro loss- and gain-of-function studies were performed to reveal the biological function of miR-192 and related mechanism of the microRNA-192/NKRF axis in lung cancer cell cisplatin resistance. RESULTS: Increased miR-192 expression was detected in A549/DDP cells compared to A549. High miR-192 expression significantly suppressed apoptosis, enhanced proliferation, and conferred resistance to cisplatin in lung cancer cells. NF-κB repressing factor (NKRF), which is involved in the regulation of the NF-κB signaling pathway, was identified as a direct target of miR-192. Overexpression of miR-192 significantly increased the nuclear protein amount and transcriptional activation of NF-κB and expression of cIAP1, cIAP2, Bcl-xl and XIAP, whereas decreased miR-192 expression did the opposite. Inhibition of the NF-κB signal pathway by curcumin reversed the effect of upregulation of miR-192 on proliferation, apoptosis and cisplatin-resistance in lung cancer cells. These results indicated that miR-192/ NKRF axis enhances the cisplatin resistance of lung cancer cells through activating the NF-κB pathway in vitro. CONCLUSIONS: MiR-192 plays a crucial role in cisplatin-resistance of lung cancer cells. Thus, MiR-192 may represent a therapeutic target for overcoming resistance to cisplatin-based chemotherapy in lung cancer.

Burden of Lung Cancer Attributable to Occupational Carcinogens from 1990 to 2019 and Projections until 2044 in China.

BACKGROUND: Little is known about trends in the lung cancer burden from the disease that can be attributed to occupational carcinogens in China. METHODS: Data regarding the lung cancer burden that can be attributed to occupational carcinogens in China were extracted from the Global Burden of Disease (GBD) study in 2019. Joinpoint regression analysis and an age-period-cohort (APC) analysis were conducted to estimate the trend of lung cancer burden as a result of occupational carcinogens from 1990 to 2019. A Bayesian APC model was used to predict the disease burden until 2044. RESULTS: The average annual percentage changes of age-standardized summary exposure values (SEVs) of occupational lung carcinogens, as well as the age-standardized population attributable fraction (PAF) of lung cancer due to occupational carcinogens, were 0.5% (95% confidence interval (CI): 0.4-0.5%) and 0.1% (95% CI: 0-0.2%), respectively. In addition, both the joinpoint regression analysis and APC analysis demonstrated significantly increased trends of age-standardized lung cancer mortality (ASMR) and age-standardized disability-adjusted life years (ASDR) as a result of occupational carcinogens. Asbestos and silica accounted for the two most important occupational lung carcinogens in China. The absolute burden is expected to increase, mainly due to population aging and the age-specific rate of illness. CONCLUSIONS: The lung cancer burden that could be attributed to occupational carcinogens significantly increased from 1990 to 2019 in China, and the absolute burden will continue to increase in the next 25 years.

MouseVenue3D: A Markerless Three-Dimension Behavioral Tracking System for Matching Two-Photon Brain Imaging in Free-Moving Mice.

Understanding the connection between brain and behavior in animals requires precise monitoring of their behaviors in three-dimensional (3-D) space. However, there is no available three-dimensional behavior capture system that focuses on rodents. Here, we present MouseVenue3D, an automated and low-cost system for the efficient capture of 3-D skeleton trajectories in markerless rodents. We improved the most time-consuming step in 3-D behavior capturing by developing an automatic calibration module. Then, we validated this process in behavior recognition tasks, and showed that 3-D behavioral data achieved higher accuracy than 2-D data. Subsequently, MouseVenue3D was combined with fast high-resolution miniature two-photon microscopy for synchronous neural recording and behavioral tracking in the freely-moving mouse. Finally, we successfully decoded spontaneous neuronal activity from the 3-D behavior of mice. Our findings reveal that subtle, spontaneous behavior modules are strongly correlated with spontaneous neuronal activity patterns.