Farmland Microhabitat Mediated by a Residual Microplastic Film: Microbial Communities and Function.

How the plastisphere mediated by the residual microplastic film in farmlands affects microhabitat systems is unclear. Here, microbial structure, assembly, and biogeochemical cycling in the plastisphere and soil in 33 typical farmland sites were analyzed by amplicon sequencing of 16S rRNA genes and ITS and metagenome analysis. The results indicated that residual microplastic film was colonized by microbes, forming a unique niche called the plastisphere. Notable differences in the microbial community structure and function were observed between soil and plastisphere. Residual microplastic film altered the microbial symbiosis and assembly processes. Stochastic processes significantly dominated the assembly of the bacterial community in the plastisphere and soil but only in the plastisphere for the fungal community. Deterministic processes significantly dominated the assembly of fungal communities only in soil. Moreover, the plastisphere mediated by the residual microplastic film acted as a preferred vector for pathogens and microorganisms associated with plastic degradation and the nitrogen and sulfur cycle. The abundance of genes associated with denitrification and sulfate reduction activity in the plastisphere was pronouncedly higher than that of soil, which increase the potential risk of nitrogen and sulfur loss. The results will offer a scientific understanding of the harm caused by the residual microplastic film in farmlands.

Effects of high manganese-cultivated seedlings on cadmium uptake by various rice (Oryza sativa L.) genotypes.

Cadmium (Cd) contamination in paddy soil threatens rice growth and food safety, enriching manganese (Mn) in rice seedlings is expected to reduce Cd uptake by rice. The effects of 250 µM Mn-treated seedlings on reducing Cd uptake of four rice genotypes (WYJ21, ZJY1578, HHZ, and HLYSM) planted in 0.61 mg kg-1 Cd-contaminated soil, were studied through the hydroponic and pot experiments. The results showed that the ZJY1578 seedling had the highest Mn level (459 µg plant-1), followed by WYJ21 (309 µg plant-1), and less Mn accumulated in the other genotypes. The relative expression of OsNramp5 (natural resistance-associated macrophage protein) was reduced by 42.7 % in ZJY1578 but increased by 23.3 % in HLYSM. The expressions of OsIRT1 (iron-regulated transporter-like protein) were reduced by 24.0-56.0 % in the four genotypes, with the highest reduction in ZJY1578. Consequently, a greater reduction of Cd occurred in ZJY1578 than that in the other genotypes, i.e., the root and shoot Cd at the tillering were reduced by 27.8 % and 48.5 %, respectively. At the mature stage, total Cd amount and distribution in the shoot and brown rice were also greatly reduced in ZJY1578, but the inhibitory effects were weakened compared to the tillering stage. This study found various responses of Cd uptake and transporters to Mn-treated seedlings among rice genotypes, thus resulting in various Cd reductions. In the future, the microscopic transport processes of Cd within rice should be explored to deeply explain the genotypic variation.

HELQ and EGR3 expression correlate with IGHV mutation status and prognosis in chronic lymphocytic leukemia.

BACKGROUND: IGHV mutation status is a crucial prognostic biomarker for CLL. In the present study, we investigated the transcriptomic signatures associating with IGHV mutation status and CLL prognosis. METHODS: The co-expression modules and hub genes correlating with IGHV status, were identified using the GSE28654, by 'WGCNA' package and R software (version 4.0.2). The over-representation analysis was performed to reveal enriched cell pathways for genes of correlating modules. Then 9 external cohorts were used to validate the correlation of hub genes expression with IGHV status or clinical features (treatment response, transformation to Richter syndrome, etc.). Moreover, to elucidate the significance of hub genes on disease course and prognosis of CLL patients, the Kaplan-Meier analysis for the OS and TTFT of were performed between subgroups dichotomized by the median expression value of individual hub genes. RESULTS: 2 co-expression modules and 9 hub genes ((FCRL1/FCRL2/HELQ/EGR3LPL/LDOC1/ZNF667/SOWAHC/SEPTIN10) correlating with IGHV status were identified by WGCNA, and validated by external datasets. The modules were found to be enriched in NF-kappaB, HIF-1 and other important pathways, involving cell proliferation and apoptosis. The expression of hub genes was revealed to be significantly different, not only between CLL and normal B cell, but also between various types of lymphoid neoplasms. HELQ expression was found to be related with response of immunochemotherapy treatment significantly (p = 0.0413), while HELQ and ZNF667 were expressed differently between stable CLL and Richter syndrome patients (p < 0.0001 and p = 0.0278, respectively). By survival analysis of subgroups, EGR3 expression was indicated to be significantly associated with TTFT by 2 independent cohorts (GSE39671, p = 0.0311; GSE22762, p = 0.0135). While the expression of HELQ and EGR3 was found to be associated with OS (p = 0.0291 and 0.0114 respectively).The Kras, Hedgehog and IL6-JAK-STAT3 pathways were found to be associating with the expression of hub genes, resulting from GSEA. CONCLUSIONS: The expression of HELQ and EGR3 were correlated with IGHV mutation status in CLL patients. Additionally, the expression of HELQ/EGR3 were prognostic markers for CLL associating with targetable cell signaling pathways.

The landscape of gene co-expression modules correlating with prognostic genetic abnormalities in AML.

BACKGROUND: The heterogenous cytogenetic and molecular variations were harbored by AML patients, some of which are related with AML pathogenesis and clinical outcomes. We aimed to uncover the intrinsic expression profiles correlating with prognostic genetic abnormalities by WGCNA. METHODS: We downloaded the clinical and expression dataset from BeatAML, TCGA and GEO database. Using R (version 4.0.2) and 'WGCNA' package, the co-expression modules correlating with the ELN2017 prognostic markers were identified (R2 ≥ 0.4, p < 0.01). ORA detected the enriched pathways for the key co-expression modules. The patients in TCGA cohort were randomly assigned into the training set (50%) and testing set (50%). The LASSO penalized regression analysis was employed to build the prediction model, fitting OS to the expression level of hub genes by 'glmnet' package. Then the testing and 2 independent validation sets (GSE12417 and GSE37642) were used to validate the diagnostic utility and accuracy of the model. RESULTS: A total of 37 gene co-expression modules and 973 hub genes were identified for the BeatAML cohort. We found that 3 modules were significantly correlated with genetic markers (the 'lightyellow' module for NPM1 mutation, the 'saddlebrown' module for RUNX1 mutation, the 'lightgreen' module for TP53 mutation). ORA revealed that the 'lightyellow' module was mainly enriched in DNA-binding transcription factor activity and activation of HOX genes. The 'saddlebrown' module was enriched in immune response process. And the 'lightgreen' module was predominantly enriched in mitosis cell cycle process. The LASSO- regression analysis identified 6 genes (NFKB2, NEK9, HOXA7, APRC5L, FAM30A and LOC105371592) with non-zero coefficients. The risk score generated from the 6-gene model, was associated with ELN2017 risk stratification, relapsed disease, and prior MDS history. The 5-year AUC for the model was 0.822 and 0.824 in the training and testing sets, respectively. Moreover, the diagnostic utility of the model was robust when it was employed in 2 validation sets (5-year AUC 0.743-0.79). CONCLUSIONS: We established the co-expression network signature correlated with the ELN2017 recommended prognostic genetic abnormalities in AML. The 6-gene prediction model for AML survival was developed and validated by multiple datasets.

MAPK14 over-expression is a transcriptomic feature of polycythemia vera and correlates with adverse clinical outcomes.

BACKGROUND: The transcriptomic signature has not been fully elucidated in PV, as well as mRNA markers for clinical variables (thrombosis, leukemic transformation, survival, etc.). We attempted to reveal and validate crucial co-expression modules and marker mRNAs correlating with polycythemia vera (PV) by weighted gene co-expression network analysis (WGCNA). MATERIAL AND METHODS: The GSE57793/26014/61629 datasets were downloaded from Gene Expression Omnibus (GEO) database and integrated into one fused dataset. By R software and 'WGCNA' package, the PV-specific co-expression module was identified, the pathway enrichment profile of which was obtained by over-representation analysis (ORA). Protein-protein interaction (PPI) network and hub gene analysis identified MAPK14 as our target gene. Then the distribution of MAPK14 expression in different disease/mutation types, were depicted based on external independent datasets. Genome-scale correlation analysis revealed the association of MAPK14 and JAK/STAT family genes. Then gene set enrichment analysis (GSEA) was performed to detect the activated and suppressed pathways associating with MAPK14 expression. Moreover, GSE47018 dataset was utilized to compare clinical variables (thrombosis, leukemic transformation, survival, etc.) between MAPK14-high and MAPK14-low groups. RESULTS: An integrated dataset including 177 samples (83 PV, 35 ET, 17 PMF and 42 normal donors) were inputted into WGCNA. The 'tan' module was identified as the PV-specific module (R2 = 0.56, p = 8e-16), the genes of which were dominantly enriched in pro-inflammatory pathways (Toll-like receptor (TLR)/TNF signaling, etc.). MAPK14 is identified as the top hub gene in PV-related PPI network with the highest betweenness. External datasets validated that the MAPK14 expression was significantly higher in PV than that of essential thrombocytosis (ET)/primary myelofibrosis (PMF) patients and normal donors. JAK2 homozygous mutation carriers have higher level of MAPK14 than that of other mutation types. The expression of JAK/STAT family genes significantly correlated with MAPK14, which also contributed to the activation of oxidated phosphorylation, interferon-alpha (IFNα) response and PI3K-Akt-mTOR signaling, etc. Moreover, MAPK14-high group have more adverse clinical outcomes (splenectomy, thrombosis, disease aggressiveness) and inferior survival than MAPK14-low group. CONCLUSION: MAPK14 over-expression was identified as a transcriptomic feature of PV, which was also related to inferior clinical outcomes. The results provided novel insights for biomarkers and therapeutic targets for PV.

Overexpression of HOXA10 is associated with unfavorable prognosis of acute myeloid leukemia.

BACKGROUND: HOXA family genes were crucial transcription factors involving cell proliferation and apoptosis. While few studies have focused on HOXA10 in AML. We aimed to investigate the prognostic significance of HOXA10. METHODS: We downloaded datasets from GEO and BeatAML database, to compare HOXA expression level between AML patients and controls. Kaplan-Meier curves were used to estimate the impact of HOXA10 expression on AML survival. The differentially expressed genes, miRNAs, lncRNAs and methylated regions between HOXA10-high and -low groups were obtained using R (version 3.6.0). Accordingly, the gene set enrichment analysis (GSEA) was accomplished using MSigDB database. Moreover, the regulatory TFs/microRNAs/lncRNAs of HOXA10 were identified. A LASSO-Cox model fitted OS to clinical and HOXA10-associated genetic variables by glmnet package. RESULTS: HOXA10 was overexpressed in AML patients than that in controls. The HOXA10-high group is significantly associated with shorter OS and DFS. A total of 1219 DEGs, 131 DEmiRs, 282 DElncRs were identified to be associated with HOXA10. GSEA revealed that 12 suppressed and 3 activated pathways in HOXA10-high group. Furthermore, the integrated regulatory network targeting HOXA10 was established. The LASSO-Cox model fitted OS to AML-survival risk scores, which included age, race, molecular risk, expression of IKZF2/LINC00649/LINC00839/FENDRR and has-miR-424-5p. The time dependent ROC indicated a satisfying AUC (1-year AUC 0.839, 3-year AUC 0.871 and 5-year AUC 0.813). CONCLUSIONS: Our study identified HOXA10 overexpression as an adverse prognostic factor for AML. The LASSO-COX regression analysis revealed novel prediction model of OS with superior diagnostic utility.

LINC00649 underexpression is an adverse prognostic marker in acute myeloid leukemia.

BACKGROUND: Long noncoding RNAs (lncRNA) play a role in leukemogenesis, maintenance, development, and therapeutic resistance of AML. While few studies have focused on the prognostic significance of LINC00649 in AML, which we aim to investigate in this present study. METHODS: We compared the expression level of LINC00649 between AML patients and healthy controls. The Kaplan-Meier curves of AML patients expressing high versus low level of LINC00649 was performed. The LINC00649 correlated genes/miRNAs/lncRNAs and methylation CpG sites were screened by Pearson correlation analysis with R (version 3.6.0), using TCGA-LAML database. The LINC00649 associated ceRNA network was established using lncBase 2.0 and miRWalk 2.0 online tools, combining results from correlation analysis. Finally, a prediction model was constructed using LASSO-Cox regression. RESULTS: LINC00649 was underexpressed in bone marrow of AML group than that in healthy control group. The patients of LINC00649-low group have significantly inferior PFS and OS. A total of 154 mRNAs, 31 miRNAs, 28 lncRNAs and 1590 methylated CpG sites were identified to be significantly correlated with LINC00649. Furthermore, the network of ceRNA was established with 6 miRNAs and 122 mRNAs. The Lasso-Cox model fitted OS/PFS to novel prediction models, which integrated clinical factors, ELN risk stratification, mRNA/miRNA expression and methylation profiles. The analysis of time-dependent ROC for our model showed a superior AUC (AUC = 0.916 at 1 year, AUC = 0.916 at 3 years, and AUC = 0.891 at 5 years). CONCLUSIONS: Low expression of LINC00649 is a potential unfavorable prognostic marker for AML patients, which requires the further validation. The analysis by LASSO-COX regression identified a novel comprehensive model with a superior diagnostic utility, which integrated clinical and genetic variables.

Bioinformatics Analysis of Key Genes and Pathways Associated with Thrombosis in Essential Thrombocythemia.

BACKGROUND Essential thrombocythemia (ET) is a form of chronic myeloproliferative neoplasm (MPN), and thrombosis is an important complication. This study aimed to use bioinformatics analysis to identify differentially expressed genes (DEGs) in ET associated thrombosis. MATERIAL AND METHODS Two datasets were identified from the Gene Expression Omnibus (GEO) database to investigate the expression profiles in ET. The GSE103176 dataset included 24 patients with ET and 15 healthy individuals with samples from CD34+ bone marrow cells. The GSE54644 dataset included 47 patients with ET and 11 healthy individuals with samples from peripheral neutrophils. GEO2R was used to screen DEGs, followed by over-representation analysis. Protein-protein interaction (PPI) network analysis and module analysis were performed using the STRING database and Cytoscape software. Hub genes were identified using the cytoHubba Cytoscape plugin, and maximal clique centrality (MCC) was identified. The MCODE Cytoscape plugin was used to identify network clusters, or highly interconnected regions. RESULTS There were 586 and 392 DEGs identified from the GSE103176 and GSE54644 datasets, respectively. The upregulated DEGs for CD34+ cells were predominantly enriched for granulocyte activation or related pathways for biological process (BP), and secretory vesicle for the cellular component (CC). The top hub genes within CD34+ cells included CXCL1, CAMP, HP, MMP8, PTX3, ORM1, LYZ, LTF, PGLYRP1, and OLFM4. CONCLUSIONS Bioinformatics analysis identified DEGs and hub genes that interacted with CD34+ cells and neutrophils that may predict an increased risk of thrombosis in patients with ET. These preliminary findings should be validated using next-generation sequencing (NGS) and clinical studies.

Detection of intracellular IgD using flow cytometry could be a novel and supplementary method to diagnose IgD multiple myeloma.

BACKGROUND: We examined whether detecting the heavy chain of cytoplasmic immunoglobulin D (IgD) by flow cytometry could be used as a supplemental method to diagnose IgD multiple myeloma (MM). METHODS: Bone marrow (BM) samples of thirty-five patients with MM were collected. Five of them were IgD MM, the rest of thirty were other subtypes of MM. Antibodies to four types of heavy chains of immunoglobulin (e.g., IgA, IgG, IgM, and IgD) were analyzed by flow cytometry in each patient's BM sample. RESULTS: The five IgD MM patients were all positive for cytoplasmic IgD. The percentage of IgD positive MM cells among nucleated cells varied from 0.4 to 12.9%. Cytoplasmic IgG was positive in eight patients with IgG MM (n = 9); cytoplasmic IgA was positive in all patients with IgA MM (n = 10); cytoplasmic IgM was positive in one patient with IgM MM (n = 1). No heavy chain was detected in light chain MM (n = 9) and non-secretory subtype (n = 1). CONCLUSIONS: Detection of cytoplasmic IgD by flow cytometry is a convenient, sensitive and supplemental method to diagnose IgD MM.

Clinicopathological implications of Tiam1 overexpression in invasive ductal carcinoma of the breast.

BACKGROUND: T-lymphoma invasion and metastasis-inducing protein 1 (Tiam1) has been implicated in tumor occurrence and progression. Recent studies have shown that high expression levels of Tiam1 protein appear to be associated with the progression of numerous human tumors. This study attempted to explore the role of Tiam1 protein in tumor progression and the prognostic evaluation of breast cancer. METHODS: The localization of the Tiam1 protein was determined in the MDA-MB-231 breast cancer cell line using immunofluorescence (IF) staining. In addition, a total of 283 breast tissue samples, including 153 breast cancer tissues, 67 ductal carcinoma in situ (DCIS) and 63 adjacent non-tumor breast tissues, were analyzed by immunohistochemical (IHC) staining of the Tiam1 protein. The correlation between Tiam1 expression and clinicopathological characteristics was evaluated by Chi-square test and Fisher's exact tests. Disease-free survival (DFS) and 10-year overall survival (OS) rates were calculated by the Kaplan-Meier method. Additionally, univariate and multivariate analyses were performed by the Cox proportional hazards regression models. RESULTS: Tiam1 protein showed a mainly cytoplasmic staining pattern in breast cancer cells; however, nuclear staining was also observed. Tiam1 protein expression was significantly higher in breast cancers (42.5 %, 65/153) and DCIS (40.3 %, 27/67) than in adjacent non-tumor tissues (12.7 %, 8/63). In addition, Tiam1 associated with tumor stage and Ki-67 expression, but negatively correlated with receptor tyrosine-protein kinase erbB-2 (Her2) expression. Moreover, survival analyses showed that DFS and 10-year OS rates were significantly lower in breast cancer patients with high Tiam1 expression than those with low Tiam1 expression. Univariate analysis suggested that molecular types, clinical stage, Her2 expression levels and Tiam1 expression levels were also significantly associated with DFS and 10-year OS rates of breast cancer patients. Furthermore, multivariate analysis suggested that Tiam1 expression is a significant independent prognostic factor along with tumor stage in patients with breast cancer. CONCLUSIONS: Tiam1 expression is frequently up-regulated in breast cancer. Tiam1 expression correlated with clinicopathological parameters, suggesting that it may be a useful prognostic biomarker and potential therapeutic target for patients with breast cancer.

Crystal structure, luminescence properties, energy transfer and thermal properties of a novel color-tunable, white light-emitting phosphor Ca9-x-yCe(PO4)7:xEu2+,yMn2.

A series of Ca9-x-yCe(PO4)7:xEu2+,yMn2+ phosphors were synthesized by a high-temperature solid-state reaction method. The as-prepared samples were characterized by XRD and EDX measurements, which showed that Eu2+ and Mn2+ could be efficiently doped into the host. Ce3+ acts concurrently as activator and sensitizer in Ca9Ce(PO4)7, and the energy transfer mechanisms between Ce3+/Eu2+ and Ce3+/Mn2+ in Ca9Ce(PO4)7 were validated and proven to be a resonant type via dipole-quadrupole and dipole-dipole interactions, respectively. Besides, there is also energy transfer from Eu2+ to Mn2+ ions. The host, Ca9Ce(PO4)7, emits blue-white light and Ca9Ce(PO4)7:xEu2+,yMn2+ phosphors emit blue-green through white to orange-red light under near-ultraviolet radiation as a result of tuning the ratio of Eu2+/Mn2+. Ca9Ce(PO4)7:0.04Eu2+,0.08Mn2+ emits white light with CIE coordinates (0.333, 0.310), a CCT of 5446 K, and a high CRI of 81. The energy transfer efficiency between Ce3+ and Mn2+ increases significantly with temperature. These results reveal that Ca9Ce(PO4)7:Eu2+,Mn2+ may be a potential candidate for white light-emitting phosphors.

NQO1 protein expression predicts poor prognosis of non-small cell lung cancers.

BACKGROUND: High-level expression of NAD(P)H: quinoneoxidoreductase 1 (NQO1) has been correlated with many types of human cancers, suggesting that NQO1 plays important roles in tumor occurrence and progression. This study attempted to explore the role of NQO1 in tumor progression and prognostic evaluation of non-small cell lung cancer (NSCLC). METHODS: Total 164 tissue samples, including 150 NSCLC paired with the adjacent non-tumor tissues and 14 normal lung tissues, were picked-up for immunohistochemical (IHC) staining of the NQO1 protein, and immunofluorescence (IF) staining was also performed to detect the subcellular localization of the NQO1 protein in A549 human lung cancer cells. The correlation between NQO1 expression and clinicopathological characteristics were evaluated by Chi-square test and Fisher's exact tests. The disease-free survival (DFS) and overall survival (OS) rates of NSCLC patients were calculated by the Kaplan-Meier method, and univariate and multivariate analyses were performed using the Cox proportional hazards regression model. RESULTS: The NQO1 protein showed a mainly cytoplasmic staining pattern in lung cancer cells, including adenocarcinoma and squamous cell carcinoma (SCC). Both positive rate and strongly positive rate of NQO1 protein expression were significantly higher in NSCLC (59.3% and 28.0%) than that in adjacent non tumor (8.0% and 1.3%) and normal lung tissues (0%). The positive rate of NQO1 was related with clinical stage and lymph node metastasis, and the strongly positive rate of NQO1 protein was significantly correlated with tumor size, poor differentiation, advanced clinical stage and lymph node metastasis in NSCLC. Additionally, survival analyses showed that the patients with NQO1 positive expression had lower OS rates compared with those with NQO1 negative expression in the groups of T1-2, T3-4, without LN metastasis and stage I-II of NSCLC, respectively; however, in the groups of patients with LN metastasis or III-IV stages, OS rate was not correlated with NQO1 expression status. Moreover, multivariate analysis suggested that NQO1 emerged as a significant independent prognostic factor along with tumor size, differentiation, lymph node metastasis and clinical stage in patients with NSCLC. CONCLUSIONS: NQO1 is upregulated in NSCLC, and it may be a useful poor prognostic biomarker and a potential therapeutic target for patients with NSCLC.

[Expression of the epithelial cell adhesion molecule in prostate cancer and its clinical significance].

OBJECTIVE: To explore the expression of the epithelial cell adhesion molecule (EpCAM) in prostate cancer (PCa) and its clinical significance. METHODS: We collected tissue samples from 63 cases of PCa, 46 cases of prostatic intraepithelial neoplasia (PIN), and 58 cases of benign prostatic hyperplasia (BPH) adjacent to PCa and determined the expression of EpCAM in the epithelial and stromal cells by immunohistochemistry. RESULTS: The positive expression rates of EpCAM in the epithelial cells were significantly higher in PCa and PIN than in PCa-adjacent BPH (98. 4 and 97. 8 vs 51.7%, P <0. 01), and so was that in the stromal cells of PCa than in those of PCa-adjacent PIN (89.5 vs 50.0%, P <0.01). The expression of EpCAM.was remarkably higher in the stromal cells of bone metastasis than in those of non-bone metastasis tissue (100. 0 vs 40. 0%, P <0. 01) but showed no statistically significant differences between the highly and poorly differentiated PCa tissues (88.5 vs 91.9%, P >0.05). CONCLUSION: The expression level of EpCAM in the stromal cells of PCa is related to the occurrence, progression, and bone metastasis of the tumor, and therefore may be used as a marker in the early diagnosis of PCa as well as a predictor of bone metastasis of the tumor.

[Yes-associated protein (YAP) promotes invasion and migration of cutaneous squamous cell carcinoma cells by activating the PI3K/AKT pathway].

Objective To investigate the expression of Yes-associated protein (YAP) in cutaneous squamous cell carcinoma (cSCC) and its effects on invasion and migration. Methods Immunohistochemical staining was used to detect the expression of YAP in cSCC, Bowen disease (BD), and adjacent normal tissues, and analyzed the correlation between YAP expression and clinicopathological characteristics of cSCC. A stable cell line in A431 cells with YAP gene silencing was established through lentiviral infection. Tetramethylrhodamine isothiocyanate (TRITC)-phalloidin staining was performed to analyze the distribution and number of microfilaments in A431 cells. TranswellTM chamber assay was performed to detect the invasion ability of cells, and scratch healing assay was used to determine the migration ability. Immunofluorescence cytochemistry was used to detected the expression of EMT-related markers, including epithelial-cadherin (E-cadherin), zinc-finger transcription factors Snail in A431 cells with YAP silencing. Western blot analysis was employed to detect the expression of E-cadherin, snail, ß-catenin, phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), phosphorylaedAKT (p-AKT), ribosomal proteinS6(S6), phosphorylatedS6 (p-S6), 4E-binding protein 1 (4EBP1), and phosphorylated 4EBP1 (p-4EBP1). ResultsThe expression of YAP was significantly higher in BD and cSCC tissues compared to adjacent tissues. The strong positive rate of YAP in cSCC tissues was associated with tumor size, differentiation and the level of invasion. However, there was no correlation between YAP expression and gender, age, tumor location, morphological type, or nerve and vascular invasion. After silencing the expression of YAP in A431 cells, the migration and invasion ability of tumor cells were significantly reduced, and cell microfilaments became thinner with reduced pseudopodia. The expression of E-cadherin was increased, while the expression of snail, ß-catenin, p-AKT, p-S6 and p-4EBP1were decreased. Conclusion YAP is highly expressed in cSCC tissues, and promotes the cell migration and invasion of cSCC cells by activating the PI3K/AKT signaling pathway and EMT.

Co-hydrothermal carbonization of municipal sludge and agricultural waste to reduce plant growth inhibition by aqueous phase products: Molecular level analysis of organic matter.

The organic matter molecular mechanism by which combined hydrothermal carbonization (co-HTC) of municipal sludge (MS) and agricultural wastes (rice husk, spent mushroom substrate, and wheat straw) reduces the inhibitory effects of aqueous phase (AP) products on pak choi (Brassica campestris L.) growth compared to HTC of MS alone is not clear. Fourier-transform ion cyclotron resonance mass spectrometry was used to characterize the differences in organic matter at the molecular level between AP from MS HTC alone (AP-MS) and AP from co-HTC of MS and agricultural waste (co-Aps). The results showed that N-bearing molecules of AP-MS and co-Aps account for 70.6 % and 54.2 %-64.1 % of all molecules, respectively. Lignins were present in the highest proportion (56.3 %-78.5 %) in all APs, followed by proteins and lipids. The dry weight of co-APs hydroponically grown pak choi was 31.6 %-47.6 % higher than that of the AP-MS. Molecules that were poorly saturated and with low aromaticity were preferentially consumed during hydroponic treatment. Molecules present before and after hydroponics were defined as resistant molecules; molecules present before hydroponics but absent after hydroponics were defined as removed molecules; and molecules absent before hydroponics but present after hydroponics were defined as produced molecules. Large lignin molecules were broken down into more unsaturated molecules, but lignins were the most commonly resistant, removed, and produced molecules. Correlation analysis revealed that N- or S-bearing molecules were phytotoxic in the AP. Tannins positively influenced the growth of pak choi. These results provide new insights into potential implementation strategies for liquid fertilizers produced from AP arising from HTC of MS and agricultural wastes.

Assessment of prolonged proteasome inhibition through ixazomib-based oral regimen on newly diagnosed and first-relapsed multiple myeloma: A real-world Chinese cohort study.

OBJECTIVE: To evaluate the effectiveness, safety, and convenience of in-class transition (iCT) from intravenous bortezomib-based induction to ixazomib-based oral regimens. METHODS: This retrospective real-world study was conducted in 16 Chinese hospitals between October 2017 and April 2023 and analyzed newly diagnosed (NDMM) and first-line relapsed multiple myeloma (FRMM) patients who attained at least a partial response from bortezomib-based induction therapy, followed by an ixazomib-based oral regimen for 2 year or until disease progression or intolerable toxicity. RESULTS: The study enrolled 199 patients, median age: 63 years old, male 55.4%, 53% as high risk (HR), and 47% as standard risk. Cytogenetic risk stratification by metaphase fluorescence in situ hybridization (M-FISH), based on the Mayo Clinic risk stratification system. The median duration of total PI therapy was 11 months, with ixazomib-based treatment spanning 6 months. At the 20-month median follow-up, 53% of patients remained on therapy. The 24-month PFS rate was 84.3% from the initiation of bortezomib-based induction and 83.4% from the start of ixazomib-based treatment. Overall response rate (ORR) was 100% post-bortezomib induction and 90% following 6 cycles of the ixazomib-based regimen. Based on the Sankey diagrams, 89.51% of patients maintained or improved their disease response after 2 cycles of iCT, 6 cycles (90.14%), and 12 cycles (80%). The HR level of Mayo was found to be a significant independent factor in a worse remission (hazard ratio (HR) 2.55; p = 0.033). Ixazomib's safety profile aligned with previous clinical trial data, with 49% of patients experiencing at least one AE of any grade. The most common AEs included peripheral neuropathy, nausea and vomiting, diarrhea, thrombocytopenia, and granulocytopenia. CONCLUSION: In the real-world Chinese MM population, NDMM and FRMM patients responded favorably to PI-based continuous therapy, demonstrating substantial response rates. The ixazomib-based iCT allows for sustained PI-based treatment, offering promising efficacy and tolerable AEs.

Ixazomib-based frontline therapy followed by ixazomib maintenance in frail elderly newly diagnosed with multiple myeloma: a prospective multicenter study.

Background: Frail elderly patients with newly diagnosed multiple myeloma (NDMM) have inferior survival and less benefit from high-dose therapies. This prospective study aimed to investigate the efficacy, safety, and quality of life (QoL) of induction treatment of ixazomib/lenalidomide/dexamethasone (IRd) and ixazomib/pegylated liposomal doxorubicin/dexamethasone (IDd) followed by ixazomib/dexamethasone (Id) maintenance therapy in frail, elderly patients with NDMM. Methods: From July 2019 to December 2021, this non-randomized concurrent controlled clinical study enrolled 120 NDMM patients aged ≥65 years with frailty defined by the International Myeloma Working Group (IMWG) frailty score or Mayo geriatric scoring system. The enrolled patients received 6-8 cycles of IRd or IDd followed by Id maintenance therapy for a minimum of 2 years at the discretion of physicians based on patient's clinical characteristics (chiCTR1900024917). Findings: The median age was 71 years and 55% of the patients were males. The overall response rate (ORR) was 82% and 77%, complete response (CR) rate was 25% and 12% for IRd and IDd groups, respectively. The difference in ORR of the Idd group minus the IRd group was -5.36% (95% CI: -18.9% to 8.19%), indicating that the ORR of the IDd group was neither inferior nor non-inferior to the IRd group. After a median follow-up of 34.3 months, the median progression-free survival (PFS) was 21.6 and 13.9 months, OS was not reached and 29.2 months in IRd and IDd groups, respectively. 28 and 33 patients discontinued induction therapy, 20 and 19 discontinued maintenance therapy in IRd and IDd groups, respectively. Cumulative Grade 3 or higher hematological adverse events (AEs) occurred in 10 of the 60 patients (17%) and non-hematological AEs occurred in 15 of the 60 patients (25%) in the IRd group, while 13 of the 60 patients (22%) and 21 of the 60 patients (35%) in the IDd group. Patients were observed with clinically significant improvement in QoL when compared with that at baseline in both IRd and IDd groups by evaluation per cycle (P < 0.0001). Interpretation: The results demonstrated that compared with IRd regimen, IDd regimen showed no significant advantage, but the survival of the IDd group was shorter than that of the IRd group, indicating an all-oral outpatient triplet regimen with IRd, which has low toxicity and has improved QoL, could be the viable first-line treatment option for frail NDMM patients. Funding: The Young Elite Scientist sponsorship program by bast of Beijing Association for Science and Technology (No. BYESS2023116) and Beijing Medical Award Foundation (No. YXJL-2018-0539-0073).

A review of freshwater benthic clams (Corbicula fluminea): Accumulation capacity, underlying physiological mechanisms and environmental applications.

Asian clams (Corbicula fluminea) have been extensively applied in biomonitoring and other environmental fields based on their high enrichment capacity and rapid response to pollutants. This review first summarizes the kinetic process of metals and organic pollutants enriched by C. fluminea and discusses the environmental behavior and application. The accumulation ability of Cu, Zn, and Mn were significantly higher than that of other metals, which were attributed to their high uptake rate constant and low elimination rate constant. The visceral mass was found to be the major burden tissue. However, large knowledge gaps existed regarding the accumulation capacity of C. fluminea for organic pollutants and nanoparticles. Moreover, physiological mechanisms underlying the accumulation of environmental pollutants were proposed. C. fluminea can improve the niche of benthic algae by ingesting pelagic algae, mitigating water eutrophication. It can also remove pathogens and parasites based on the biological assimilation of nonspecific immunity, interrupting disease transmission. The novel insight into the application of C. fluminea in wastewater treatment further broadens the range of pest management strategies and offers the feasibility of blocking the spread of invasive bivalves.

Predicting leukemic transformation in myelodysplastic syndrome using a transcriptomic signature.

Background: For prediction on leukemic transformation of MDS patients, emerging model based on transcriptomic datasets, exhibited superior predictive power to traditional prognostic systems. While these models were lack of external validation by independent cohorts, and the cell origin (CD34+ sorted cells) limited their feasibility in clinical practice. Methods: Transformation associated co-expressed gene cluster was derived based on GSE58831 ('WGCNA' package, R software). Accordingly, the least absolute shrinkage and selection operator algorithm was implemented to establish a scoring system (i.e., MDS15 score), using training set (GSE58831 originated from CD34+ cells) and testing set (GSE15061 originated from unsorted cells). Results: A total of 68 gene co-expression modules were derived, and the 'brown' module was recognized to be transformation-specific (R2 = 0.23, p = 0.005, enriched in transcription regulating pathways). After 50,000-times LASSO iteration, MDS15 score was established, including the 15-gene expression signature. The predictive power (AUC and Harrison's C index) of MDS15 model was superior to that of IPSS/WPSS in both training set (AUC/C index 0.749/0.777) and testing set (AUC/C index 0.933/0.86). Conclusion: By gene co-expression analysis, the crucial gene module was discovered, and a novel prognostic system (MDS15) was established, which was validated not only by another independent cohort, but by a different cell origin.