Risk factors analysis and the establishment of nomogram prediction model for PICC-related venous thrombosis in patients with lymphoma: a double-center cohort-based case-control study.

Objective: The objective of this study is to examine the risk factors associated with the occurrence of PICC-Related Venous Thrombosis (PICC-RVTE) in individuals diagnosed with lymphoma, as well as to develop a predictive risk nomogram model. Methods: A total of 215 patients with lymphoma treated at Yunnan Provincial Tumor Hospital from January 2017 to December 2020 were retrospectively evaluated as the training cohort; 90 patients with lymphoma treated at the Department of Oncology of the First People's Hospital of Anning, Affiliated to Kunming University of Science and Technology during the January 2021 to September 2023 were evaluated as the validation cohort. Independent influencing factors were analyzed by logistic regression, a nomogram was developed and validated, and the model was evaluated using internal and external data cohorts for validation. Results: A total of 305 lymphoma patients were selected and 35 (11.48%) PICC-RVTE occurred, the median time was 13 days. The incidence within 1-2week was 65.71%. Multivariate analysis suggested that the activity amount, thrombosis history(within the last 12 months), ATIII, Total cholesterol and D-dimer levels were independently associated with PICC-RVTE, and a nomogram was constructed based on the multivariate analysis. ROC analysis indicated good discrimination in the training set (area under the curve [AUC] = 0.907, 95%CI:0.850-0.964) and the testing set (AUC = 0.896, 95%CI: 0.782-1.000) for the PICC-RVTE nomogram. The calibration curves showed good calibration abilities, and the decision curves indicated the clinical usefulness of the prediction nomograms. Conclusions: Patients should be advised to undergo color Doppler ultrasound system testing within two week after the implantation of a PICC catheter to detect PICC-RVTE at an early stage. The validated nomogram can be used to predict the risk of catheter-related thrombosis (CRT) in patients with lymphoma who received at least one chemotherapy after PICC catheterization, no bleeding tendency, no recent history of anticoagulant exposure and no severe heart, lung, renal insufficiency. This model has the potential to assist clinicians in formulating individualized treatment strategies for each patient.

Anti-EGFR ScFv functionalized exosomes delivering LPCAT1 specific siRNAs for inhibition of lung cancer brain metastases.

Brain metastasis (BM) is one of the leading causes of cancer-related deaths in patients with advanced non-small cell lung cancer (NSCLC). However, limited treatments are available due to the presence of the blood-brain barrier (BBB). Upregulation of lysophosphatidylcholine acyltransferase 1 (LPCAT1) in NSCLC has been found to promote BM. Conversely, downregulating LPCAT1 significantly suppresses the proliferation and metastasis of lung cancer cells. In this study, we firstly confirmed significant upregulation of LPCAT1 in BM sites compared to primary lung cancer by analyzing scRNA dataset. We then designed a delivery system based on a single-chain variable fragment (scFv) targeting the epidermal growth factor receptor (EGFR) and exosomes derived from HEK293T cells to enhance cell-targeting capabilities and increase permeability. Next, we loaded LPCAT1 siRNA (siLPCAT1) into these engineered exosomes (exoscFv). This novel scFv-mounted exosome successfully crossed the BBB in an animal model and delivered siLPCAT1 to the BM site. Silencing LPCAT1 efficiently arrested tumor growth and inhibited malignant progression of BM in vivo without detectable toxicity. Overall, we provided a potential platform based on exosomes for RNA interference (RNAi) therapy in lung cancer BM.

Multitask deep learning for prediction of microvascular invasion and recurrence-free survival in hepatocellular carcinoma based on MRI images.

BACKGROUND AND AIMS: Accurate preoperative prediction of microvascular invasion (MVI) and recurrence-free survival (RFS) is vital for personalised hepatocellular carcinoma (HCC) management. We developed a multitask deep learning model to predict MVI and RFS using preoperative MRI scans. METHODS: Utilising a retrospective dataset of 725 HCC patients from seven institutions, we developed and validated a multitask deep learning model focused on predicting MVI and RFS. The model employs a transformer architecture to extract critical features from preoperative MRI scans. It was trained on a set of 234 patients and internally validated on a set of 58 patients. External validation was performed using three independent sets (n = 212, 111, 110). RESULTS: The multitask deep learning model yielded high MVI prediction accuracy, with AUC values of 0.918 for the training set and 0.800 for the internal test set. In external test sets, AUC values were 0.837, 0.815 and 0.800. Radiologists' sensitivity and inter-rater agreement for MVI prediction improved significantly when integrated with the model. For RFS, the model achieved C-index values of 0.763 in the training set and ranged between 0.628 and 0.728 in external test sets. Notably, PA-TACE improved RFS only in patients predicted to have high MVI risk and low survival scores (p < .001). CONCLUSIONS: Our deep learning model allows accurate MVI and survival prediction in HCC patients. Prospective studies are warranted to assess the clinical utility of this model in guiding personalised treatment in conjunction with clinical criteria.

Application of contrast-enhanced ultrasound in the diagnosis of tuberous vas deferens tuberculosis.

BACKGROUND: To assess the value of contrast-enhanced ultrasound (CEUS) in the diagnosis of tuberous vas deferens tuberculosis (VD TB) and improve the positive diagnostic rate of VD TB. METHODS: CEUS and routine ultrasound (US) images of 17 patients with tuberous VD TB confirmed by surgery, pathology, or laboratory semen examination were retrospectively analyzed and summarized, and the positive rates of both imaging techniques were compared. RESULTS: The 19 VD lesions of the 17 patients were divided into two types according to the CEUS findings: Type I and Type II, and type II was divided into Types IIa, IIb, and IIc. Of the nodules with transverse diameters > 1 cm, 100% presented as type II. Of the nodules with transverse diameters < 1 cm, 37.5% (3/8) presented as type I and 62.5% (5/8) presented as type II. The sonographic manifestations of tuberous VD TB were hypoechoic and mixed echoic. The positive diagnostic rate was 89.5% for CEUS and 68.4% for US, but the difference was not significant (χ2 = 2.533; P = 0.111). CONCLUSIONS: CEUS was able to show the blood supply characteristics of tuberous VD TB, the internal necrosis of nodules was more easily observed by CEUS than by routine US, which is helpful for the diagnosis of tuberous VD TB.

8-hydroxyquinoline-N-oxide copper(II)- and zinc(II)-phenanthroline and bipyridine coordination compounds: Design, synthesis, structures, and antitumor evaluation.

Fourteen novel tumor-targeting copper(II) and zinc(II) complexes, [Cu(ONQ)(QD1)(NO3)]·CH3OH (NQ3), [Cu(ONQ)(QD2)(NO3)] (NQ2), [Cu(NQ)(QD2)Cl] (NQ3), [Cu(ONQ)(QD1)Cl] (NQ4), [Cu(ONQ)(QD3)](NO3) (NQ5), [Cu(ONQ)(QD3)Cl] (NQ6), [Zn(ONQ)(QD4)Cl] (NQ7), [Zn(ONQ)(QD1)Cl] (NQ8), [Zn(ONQ)(QD5)Cl] (NQ9), [Zn(ONQ)(QD2)Cl] (NQ10), [Zn(ONQ)(QD6)Cl] (NQ11), [Zn(ONQ)(QD7)Cl] (NQ12), and [Zn(ONQ)(QD3)Cl] (NQ13) supported on 8-hydroxyquinoline-N-oxide (H-ONQ), 2,2'-dipyridyl (QD1), 5,5'-dimethyl-2,2'-bipyridyl (QD2), 1,10-phenanthroline (QD3), 4,4'-dimethoxy-2,2'-bipyridyl (QD4), 4,4'-dimethyl-2,2'-bipyridyl (QD5), 5-chloro-1,10-phenanthroline (QD6), and bathophenanthroline (QD7), were first synthesized and characterized using various spectroscopic techniques. Furthermore, NQ1-NQ13 exhibited higher antiproliferative activity and selectivity for cisplatin-resistant SK-OV-3/DDP tumor cells (CiSK3) compared to normal HL-7702 cells based on results obtained from the cell counting Kit-8 (CCK-8) assay. The complexation of copper(II) ion with QD2 and ONQ ligands resulted in an evident increase in the antiproliferation of NQ1-NQ6, with NQ6 exhibiting the highest antitumor potency against CiSK3 cells compared to NQ1-NQ5, H-ONQ, QD1-QD7, and NQ7-NQ13 as well as the reference cisplatin drug with an IC50 value of 0.17 ± 0.05 µM. Mechanistic studies revealed that NQ4 and NQ6 induced apoptosis of CiSK3 cells via mitophagy pathway regulation and adenosine triphosphate (ATP) depletion. Further, the differential induction of mitophagy decreased in the order of NQ6 > NQ4, which can be attributed to the major impact of the QD3 ligand with a large planar geometry and the Cl leaving group within the NQ6 complex. In summary, these results confirmed that the newly synthesized H-ONQ copper(II) and zinc(II) coordination metal compounds NQ1-NQ13 exhibit potential as anticancer drugs for cisplatin-resistant ovarian CiSK3 cancer treatment.

P2RY13 is a prognostic biomarker and associated with immune infiltrates in renal clear cell carcinoma: A comprehensive bioinformatic study.

Background and Aims: Clear cell renal cell carcinoma (ccRCC) is a common and aggressive form of cancer with a high incidence globally. This study aimed to investigate the role of P2RY13 in the progression of ccRCC and elucidate its mechanism of action. Methods: Gene Expression Omnibus and The Cancer Genome Atlas databases were used to extract gene expression profiles of ccRCC. These profiles were annotated and visualized by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses, as well as Gene Set Enrichment Analysis (GSEA). The STRING database was used to establish a protein-protein interaction network and to analyze the functional similarity. The GEPIA2 database was used to predict survival associated with hub genes. Meanwhile, the TIMER2.0 database was used to assess immune cell infiltration and its link with the hub genes. Immunohistochemistry (IHC) was used to determine the difference between ccRCC and adjacent normal tissue. Results: We identified 272 differentially expressed genes (DEGs). GO and KEGG analyses suggested that DEGs were primarily involved in lymphocyte activation, inflammatory response, immunological effector mechanism pathways. By cytohubba, the 20 highest-scoring hub genes were screened to identify critical genes in the protein-protein interaction network linked with ccRCC. Resting dendritic cells, CD8 T cells, and activated mast cells all showed a significant positive correlation with these hub genes. Moreover, a higher immune score was associated with increased prognostic risk scores, which in turn correlated with a poorer prognosis. IHC revealed that P2RY13 was expressed at higher levels in ccRCC compared to para-cancer tissues. Conclusion: Identifying the DEGs will aid in the understanding of the causes and molecular mechanisms involved in ccRCC. P2RY13 may play a pivotal role in the progression and prognosis of ccRCC, potentially driving carcinogenesis though immune system mechanisms.

Discovery and identification of the prognostic significance and potential mechanism of FMO2 in breast cancer.

BACKGROUND: Flavin containing dimethylaniline monoxygenase 2 (FMO2), is downexpressed in diverse tumors and displays vital roles in tumorigenesis. However, the prognostic value and potential mechanism of FMO2 in breast cancer remain unclear. METHODS: The expression of FMO2 was analyzed and the relationship between FMO2 expression level and clinical indicators in breast cancer was analyzed. Then the prognostic value of FMO2 in breast cancer was assessed. The FMO2-correlated genes were obtained, and the highest-ranked gene was chosen. The expression, therapeutic responder analysis, and gene set enrichment analysis of the highest-ranked gene were conducted. RESULTS: FMO2 was downregulated in breast cancer and was closely related to clinical indicators. Patients with decreased FMO2 expression showed poor overall survival, post-progression survival, relapse-free survival, and distant metastasis-free survival. FMO2 correlates with N/ER/PR subgroups in breast cancer and patients with high FMO2 levels were sensitive to anti-programmed cell death protein 1, anti-programmed death-ligand 1, and anti-cytotoxic T-lymphocyte antigen 4 immunotherapies. Mechanically, FMO2 was positively and highly correlated with secreted Frizzled-related protein 1 (SFRP1), which was downregulated in breast cancer due to hypermethylation. Moreover, SFRP1 was correlated to pathological complete response and relapse-free survival status at 5 years regardless of any chemotherapy, hormone therapy, and anti-HER2 therapy. Gene set enrichment analysis revealed enrichment of component and coagulation cascades, focal adhesion, protein export, and spliceosome. CONCLUSIONS: FMO2 was lower expressed in breast cancer than normal tissues and contributes to subtype classification and prognosis prediction with co-expressed SFRP1.

Combined iron (III) chloride/sodium citrate with enzymatic hydrolysis for xylo-oligosaccharides and monosaccharides production from poplar.

Currently, the production of xylo-oligosaccharides (XOS) from lignocelluloses by chelating system hydrolysis has not been investigated. Herein, iron (III) chloride/sodium citrate (IC/SC) chelating system hydrolysis and xylanase hydrolysis were used to produce XOS from poplar. Then, the delignification of IC/SC-hydrolyzed poplar was performed by p-toluenesulfonic acid (p-TsOH) pretreatment to increase the accessibility of cellulase. The results demonstrated that 42.3% of XOS with an extremely low by-product (xylose/XOS = 0.11) was produced from poplar by 50 mM IC/SC hydrolysis (molar ratio of 1:1, 170 °C, 60 min) and xylanase hydrolysis. The second step IC/SC hydrolysis and xylanase hydrolysis of poplar increased the yield of XOS to 51.3%. Finally, the glucose yield of p-TsOH-pretreated poplar (60% p-TsOH, 70 °C, 30 min) was greatly increased from 37.5% to 83.8% by cellulase hydrolysis with Tween 80 addition. The novel strategy proposed in this work was feasible for XOS and monosaccharides production from poplar.

Cancer survival analysis and spatial distribution during 2014-2016 in Shandong Province, China.

We aimed to analyse cancer survival and its spatial distribution in Shandong Province. A total of 609,861 cancer cases from 2014 to 2016 were included in the analysis. Survival analysis was performed using strs in Stata. Spatial analysis was performed with GeoDa to determine measures of global and local spatial autocorrelation. Hotspot analysis was used to identify spatial clusters of high values (hotspots) and low values (cold spots) through ArcGIS. The 5-year relative survival rates were 37.85% for all cancers combined, 29.29% for males and 48.88% for females. After age standardisation, the survival rates were 34.47% for all cancers, 28.43% for males and 41.56% for females. Cancers with higher survival rates included thyroid (78.80%), breast (69.52%), uterus (64.51%) and bladder (62.54%) cancers. However, cancers with lower survival rates included pancreatic (11.34%), liver (13.19%), lung (18.39%), bone (19.71%), gallbladder (19.78%), oesophagus (24.52%), and stomach (28.85%) cancers and leukaemia (26.30%). Cancer survival rates in urban areas (37.53%) were higher than those in rural areas (32.83%). From the geographic distribution of cancer survival, we observed that the survival rate displayed a downward trend from east to west and from north to south. The hotspot analysis revealed that some counties of Qingdao, Jinan, Zibo, Dongying and Yantai cities were hotspots, whereas almost all counties of Linyi city and some counties of Weifang, Heze, Rizhao, and Dezhou cities were cold spots. In conclusion, the cancer survival rate in Shandong is still lower than that in China overall. The early diagnosis and treatment of lung and digestive tract cancers need to be further strengthened. Nevertheless, our results reflect a critical first step in obtaining and reporting accurate and reliable estimates of survival in Shandong.

Simulation of a tumor cell flowing through a symmetric bifurcated microvessel.

Microvessel bifurcations serve as the major sites of tumor cell adhesion and further extravasation. In this study, the movement, deformation, and adhesion of a circulating tumor cell flowing in a symmetric microvessel with diverging and converging bifurcations were simulated by dissipative particle dynamics combined with a spring-based network model. Effects of the initial position of the CTC, externally-applied acceleration and the presence of RBCs on the motion of the CTC were investigated. The results demonstrated that the CTC released at the centerline of the parent vessel would attach to the vessel wall when arriving at the apex of diverging bifurcation and slide into the daughter branch determined by its centroid deflection and finally form firm adhesion at relatively lower flow rates. As the external acceleration increases, the increasing shear force enlarges the contact area for the adherent CTC on the one hand and reduces the residence time on the other hand. With the presence of RBCs in the bloodstream, the collision between the adherent tumor cell at the diverging bifurcation and flowing RBCs promotes the firm adhesion of CTC at lower flow rates.

SNHG9/miR-214-5p/SOX4 feedback loop regulates osteosarcoma progression.

Osteosarcoma (OS) is a high-grade, aggressive bone sarcoma. LncRNAs play a key regulatory role in controlling biological and pathological processes. The expression of lncRNA SNHG9 varies among different cancer tissues, and the role of SNHG9 in OS progression is unclear. In this study, we found SNHG9 overexpression in OS tissues and cells. In addition, downregulated SNHG9 expression impaired the proliferation, migration, and invasion abilities of OS cells. SNHG9 expression was positively regulated by the transcription factor SOX4. SNHG9 interacted with miR-214-5p as a molecular sponge and SOX4 was identified as the target of miR-214-5p. The interaction affected the expression of SNHG9, miR-214-5p, and SOX4, and regulated OS cell proliferation, migration, and invasion. Therefore, the SNHG9/miR-214-5p/SOX4 feedback loop performs an important role in OS progression and might be used as a new potential therapeutic target for the treatment of OS.

Correlation between physical characteristics of biopsy specimen and disease of cervical lymph node after contrast-enhanced ultrasound.

BACKGROUND: To investigate the correlation between physical characteristics and disease of cervical lymph node biopsy specimens after contrast-enhanced ultrasound. METHODS: All patients were biopsied after CEUS, 235 patients were divided into three groups A, B and C according to the physical characteristics of specimens: 92 patients in group A were complete tissue specimens; 113 patients in group B were discontinuous tissue specimens. There were 30 patients in group C, including a small number of tissue and floc, purulent and bloody specimens. Pathological examination, pathogen culture examination and Gene X-Pert MIB examination were completed for all patients in the three groups, and statistical analysis was conducted on the integrity and traits of the specimens. RESULTS: Group A included 92 intact tissue specimens, 21 with reactive hyperplasia, 17 with lymphoma, 12 with metastatic carcinoma, 13 with lymphadenopathy, 15 with necrotizing lymphadenitis, and rare lymphadenopathy. In group B, 113 patients were treated with intermittent tissue specimens, including infected lymph nodes, lymphoma in 1 case, metastatic carcinoma in 3 cases and sarcoidosis in 1 case. There were 30 patients in group C, including a small amount of tissue and floc, purulent and bloody specimens, all of which were infected lymph nodes. The χ2 value of malignant and benign lymph nodes was 42.401, p = 0.000. CONCLUSION: The physical characteristics of cervical lymph node biopsy specimens after CEUS are correlated with the disease, which has guiding significance for postoperative specimen selection.

ß-Carotene extracted from Blakeslea trispora attenuates oxidative stress, inflammatory, hepatic injury and immune damage induced by copper sulfate in zebrafish (Danio rerio).

ß-Carotene, as a kind of potent antioxidant compounds, has gained extensive attention. Blakeslea trispora, a filiform aerobic fungus, has been proposed as a natural source of ß-carotene for commercial exploitation. However, it has not yet been investigated whether ß-carotene extracted from Blakeslea trispora can attenuate oxidative stress, inflammatory, liver injury and immune damage of zebrafish (Danio rerio) exposed to copper sulfate (CuSO4). In this study, we evaluated the effects of ß-carotene on migration of GFP-labeled neutrophils, histological changes of liver, markers of oxidative, inflammatory cytokines and transaminase analysis, as well as the expression and activities of apoptosis, immune-related certain genes in zebrafish treated with different concentrations of ß-carotene (0, 10, 20, 40 µg/mL) after exposure to CuSO4. The results indicated that ß-carotene reduced migration of neutrophils and released liver damage. What's more, ß-carotene was found to reduce the index levels of oxidative stress response (HMOX-1, reactive oxygen species (ROS), NADPH, MDA), inflammatory factors (interleukine-1ß (IL-1ß), interleukine-6 (IL-6), interleukine-8 (IL-8), tumor necrosis factor-α (TNF-α)), liver function protein (AST, ALT) which increased by CuSO4. ß-Carotene also promoted the activities of SOD, GSH-Px, ACP, AKP and LZM and increased the protein of immune-related factors, IgM and IFN-γ after exposure to CuSO4. Thus, our results demonstrate that ß-carotene has an antioxidant, anti-inflammatory and hepatoprotective activity and participation in immunoregulation.

Long non-coding RNA BBOX1-AS1 exacerbates esophageal squamous cell carcinoma development by regulating HOXB7/ß-catenin axis.

Mounting evidence suggests that long non-coding RNAs play a critical role in the occurrence and development of human malignancies. Nonetheless, it remains unknown whether Gamma-Butyrobetaine Hydroxylase 1-Antisense RNA 1 (BBOX1-AS1) participates in the regulation of esophageal squamous cell carcinoma (ESCC) carcinogenesis. Herein, we validated that BBOX1-AS1 was notably overexpressed in ESCC tissues compared to the adjacent non-tumor tissues and significantly correlated with tumor sizes. BBOX1-AS1 enhanced the malignant behavior of ESCC cells in vitro, such as cell proliferation, migration, and invasion. In addition, knockdown of BBOX1-AS1 augmented the proportion of apoptotic cells in ESCC cells. Mechanistically, BBOX1-AS1 regulated HOXB7 expression, and rescue experiments indicated that silencing of HOXB7 could abolish the malignant phenotypes mediated by BBOX1-AS1 to a certain extent. Moreover, HOXB7 participated in the activation of the Wnt/ß-catenin signaling pathway. In summary, our findings substantiated that BBOX1-AS1 could activate the Wnt/ß-catenin pathway by upregulating HOXB7 expression to promote ESCC progression, providing a rationale to develop novel therapeutic approaches.

The value of multimodal ultrasonography in differential diagnosis of tuberculous and non-tuberculous superficial lymphadenitis.

BACKGROUND: To investigate the value of multimodal ultrasonography in differentiating tuberculosis from other lymphadenopathy. METHODS: Sixty consecutive patients with superficial lymphadenopathy treated at our hospital from January 2017 to December 2018 were categorized into four types based on the color Doppler ultrasound, five types based on contrast-enhanced ultrasound, and five types based on elastography. Sensitivity and specificity were calculated of all the three imaging, including color Doppler examination, contrast-enhanced ultrasound and one individual multimodal method, for detecting lymph nodes. RESULTS: A total of 60 patients were included in the final analysis. Of those, Mycobacterium tuberculosis was positive in 38 patients and negative in 22 patients. Among the 38 patients who were positive for Mycobacterium tuberculosis, of which 23 had a history of pulmonary tuberculosis, accounting for 60.53% of the positive cases, and the remaining patients did not combine lesions of other organs. Among the 60 superficial lymph nodes, 63.3% presented with tuberculous lymphadenitis. The sensitivity, specificity, and accuracy of the color Doppler examination were 73.68%, 68.18%, and 71.67%, respectively. The sensitivity, specificity and accuracy of contrast-enhanced ultrasound were 89.47%, 63.64% and 80.00%, respectively. The sensitivity, specificity and accuracy of the elastography were 63.16%, 63.64% and 63.33%, respectively. The sensitivity, specificity and accuracy of one individual multimodal method were 42.11%, 95.45% and 61.67%, respectively. The sensitivity, specificity and accuracy of all modes combined were 100.00%, 27.27% and 73.33%, respectively. CONCLUSION: Multimodal ultrasonography has high predictive value for the differential diagnosis of superficial tuberculous lymphadenitis.

Region-Specific Biomarkers and Their Mechanisms in the Treatment of Lung Adenocarcinoma: A Study of Panax quinquefolius from Wendeng, China.

Panax quinquefolius, a popular medicinal herb, has been cultivated in China for many years. In this work, the region-specific profiles of metabolites in P. quinquefolius from Wendeng was investigated using liquid-chromatography-quadrupole-time-of-flight-(LC-Q-TOF)-based metabolomics analysis. The three most abundant biomarkers, identified as ginsenoside Rb3, notoginsenoside R1, and ginsenoside Rc, were the representative chemical components employed in the network pharmacology analysis. In addition, molecular docking and western blotting analyses revealed that the three compounds were effective binding ligands with Hsp90α, resulting in the inactivation of SRC and PI3K kinase, which eventually led to the inactivation of the Akt and ERK pathways and lung cancer suppression. The outcomes obtained herein demonstrated the intriguing chemical characteristics and potential functional activities of P. quinquefolius from Wendeng.

Experimental Study of Chloride Resistance of Polypropylene Fiber Reinforced Concrete with Fly Ash and Modeling.

Herein, the paper reports an experimental investigation lasting one year on the chloride resistance of polypropylene fiber (PF) reinforced concrete with fly ash (FA). Four influential factors at four levels were studied, viz. water to binder ratio (w/b) (0.53, 0.34, 0.29, and 0.25), PF dosage (0%, 0.06%, 0.08%, and 0.1% in volume basis of the total volume of concrete), FA content (0%, 15%, 25%, and 35% in mass substitution ratio of cement) and concentration of NaCl solution (0%, 3%, 5%, and 7%). Dry-wet cyclic immersion and long-term soaking were taken into consideration in addition to the aforementioned factors. A L16(44) orthogonal table was used to sequence influencing factors and to determine the optimal combination. Results showed that 7% NaCl solution caused the highest chloride content in 0-5 mm depth, whilst the w/b ratio of 0.25 curbed the chloride penetration within 10 mm even for concrete subjected to dry-wet cyclic immersion for 360 d. Subsequently, a respond surface model (RSM) basing on polynomials was constructed to visually evaluate the effect of PF dosage and FA content. Results clarified that a cubic model was more precise and PF dosage and FA content turned out to have the positive facilitation to chloride resistance. The positive effect of PF however is not consistent and commensurate for concrete with varied fly ash content. Finally, a fuzzy logic based nonlinear model accommodating all seven influencing factors was verified to be proper and adaptive in predicting chloride content.

LncRNA LOXL1-AS1 promotes esophageal squamous cell carcinoma progression by targeting DESC1.

Recently, ample evidence indicated that numerous aberrantly expressed long non-coding RNAs (lncRNAs) participated in the development of multiple malignancies. However, the expression and function of lncRNA LOXL1-AS1 in mediating esophageal squamous cell carcinoma (ESCC) carcinogenesis remains largely elusive. Here we validated that LOXL1-AS1 was significantly upregulated in ESCC tissues compared with the corresponding adjacent non-neoplastic tissues, and LOXL1-AS1 expression was positively correlated with ESCC patients' lymph node metastasis. Besides, LOXL1-AS1 knockdown impaired ESCC cells proliferation, migration and invasion capabilities in vitro. Furthermore, inhibiting LOXL1-AS1 in ESCC cells increased the percentage of cells at the G1 phase, accompanied by reducing in S phase in contrast to scramble control, and silencing of LOXL1-AS1 evoked ESCC cell apoptosis. From high throughput RNA sequencing (RNA-seq) analysis, we identified that differentially expressed in squamous cell carcinoma 1 (DESC1) was a critical downstream target of LOXL1-AS1. Taken together, we demonstrated the function and mechanism of LOXL1-AS1 in contributing ESCC progression for the first time, and indicated LOXL1-AS1 may be a novel therapeutic biomarker of ESCC.

METTL3 restrains papillary thyroid cancer progression via m6A/c-Rel/IL-8-mediated neutrophil infiltration.

Growing evidence indicates that N6-methyladenosine (m6A) is the most pervasive RNA modification in eukaryotic cells. However, the specific role of METTL3 in papillary thyroid carcinoma (PTC) initiation and development remains elusive. Here we found that downregulation of METTL3 was correlated with malignant progression and poor prognosis in PTC. A variety of gain- and loss-of-function studies clarified the effect of METTL3 on regulation of growth and metastasis of PTC cells in vitro and in vivo. By combining RNA sequencing (RNA-seq) and methylated RNA immunoprecipitation sequencing (meRIP-seq), our mechanistic studies pinpointed c-Rel and RelA as downstream m6A targets of METTL3. Disruption of METTL3 elicited secretion of interleukin-8 (IL-8), and elevated concentrations of IL-8 promoted recruitment of tumor-associated neutrophils (TANs) in chemotaxis assays and mouse models. Administration of the IL-8 antagonist SB225002 substantially retarded tumor growth and abolished TAN accumulation in immunodeficient mice. Our findings revealed that METTL3 played a pivotal tumor-suppressor role in PTC carcinogenesis through c-Rel and RelA inactivation of the nuclear factor κB (NF-κB) pathway by cooperating with YTHDF2 and altered TAN infiltration to regulate tumor growth, which extends our understanding of the relationship between m6A modification and plasticity of the tumor microenvironment.

LncRNA FAM83A-AS1 promotes ESCC progression by regulating miR-214/CDC25B axis.

Background: Recent researches have pinpointed that long non-coding RNA (lncRNA) was tightly related to the carcinogenesis. However, the function of lncRNA in esophageal cell squamous carcinoma (ESCC) remains to be explored. In the current study, we assessed the expression pattern and the biological function of FAM83A-AS1 in ESCC. Methods: qRT-PCR was used to detect the expression of FAM83A-AS1, miR-214, and CDC25B expression in ESCC tissues and cell lines. CCK-8, transwell, apoptosis and cell cycle assays were performed to define the function of FAM83A-AS1 in ESCC cells. Furthermore, the regulation of miR-214 by FAM83A-AS1 was defined by qRT- PCR and rescue assays. In addition, the association between CDC25B, miR-214, CDC25B was confirmed by qRT-PCR. Results: Here, we discovered that FAM83A-AS1 was strongly expressed in ESCC tissues. FAM83A-AS1 abundance was associated with TNM stages and the differentiation grade of ESCC patients. The receiver operating characteristic curve (ROC) analysis indicated the high accuracy of FAM83A-AS1 in ESCC diagnosis. Functionally, inhibiting FAM83A-AS1 repressed cell proliferation, migration, and invasion in ESCC. In addition, we found that FAM83A-AS1 accelerated the cell cycle while inhibited cell apoptosis. Mechanistically, we found that FAM83A-AS1 regulated miR-214 expression, and there was a negative correlation between miR-214 and FAM83A-AS1 in ESCC. Rescue assay indicated that miR-214 could impair the suppressing effect of cell migration induced by FAM83A-AS1 depletion. Furthermore, CDC25B was a direct target of miR-214, and FAM83A-AS1 enhanced CDC25B expression while miR-214 positively CDC25B expression in ESCC. Conclusions: Collectively, we concluded that FAM83A-AS1 facilitated ESCC progression by regulating the miR-214/CDC25B axis. Our study showed FAM83A-AS1 may act as a promising target for ESCC diagnosis and therapy.