Increased LACTB2 Expression Regulates Oxidative Phosphorylation and mTORC1 Signaling of Colorectal Cancer.

This study aimed to investigate the mechanisms of LACTB2 in colorectal cancer (CRC). Microarrays and sequencing data of CRC were acquired from UCSC Xena, GTEx, Gene Expression Omnibus, and TCGA. Pooled analysis of the mRNA expression of LACTB2 in CRC was performed using Stata software. The protein expression of LACTB2 in CRC tissues was evaluated by immunohistochemistry. The relationship between immune cell infiltration and LACTB2 expression was investigated using CIBERSORT. The potential signaling pathways and biological mechanisms of LACTB2 were explored using GSEA, KEGG, and GO. Subsequently, further screening of small molecular compounds with potential therapeutic effects on CRC was conducted through the HERB database, followed by molecular docking studies of these compounds with the LACTB2 protein. The integration and analysis of expression data obtained from 2294 CRC samples and 1286 noncancerous colorectal samples showed that LACTB2 was highly expressed in CRC. Immunohistochemistry performed on in-house tissue samples confirmed that LACTB2 protein expression was upregulated in CRC. CIBERSORT revealed lower B cell infiltration levels in the high LACTB2 expression group than in the low expression group. GO, KEGG, and GSEA analyses showed that LACTB2 expression and genes positively correlating with it were mainly related to DNA synthesis and repair, mitochondrial translational elongation and translational termination, phosphorylation, and mTORC1 signaling. Finally, molecular docking simulations confirmed the ability of quercitin to target and bind to LACTB2. This is the first study to demonstrate that LACTB2 is upregulated in CRC. LACTB2 promotes colorectal tumorigenesis and tumor progression.

Combination of concept maps and case-based learning in a flipped classroom: A mixed-methods study.

AIM: This study aimed to evaluate the impact of a hybrid learning method on the academic achievements, learning skills and experiences of undergraduate nursing students. BACKGROUND: Case-based learning is a student-centered approach that is commonly integrated into the flipped classroom model in nursing education. However, effectively combining the flipped classroom model and case-based learning into a hybrid learning format is challenging. To address this gap, this study integrated concept maps with case-based learning and the flipped classroom and evaluated the impact of this hybrid learning method on the academic achievements, learning skills and experiences of undergraduate nursing students. DESIGN: A mixed-methods approach, including a quasi-experimental study and semi-structured interviews, was employed. METHODS: A total of 277 undergraduate nursing students participated, with 136 students in the control group undergoing case-based learning and 141 students in the experimental group taught using the hybrid learning approach, which combined concept maps, case-based learning and a flipped classroom. The study assessed self-directed learning, critical thinking, learning strategy and curriculum grades in both groups before and after the intervention. Additionally, students in the experimental group participated in semi-structured interviews. RESULTS: The quantitative findings indicated that both case-based learning and the hybrid learning method (combined concept maps, case-based learning and a flipped classroom) had similar impacts on the curriculum grades, self-directed learning, cognitive maturity and learning strategy of nursing students. The qualitative results further demonstrated how the hybrid approach facilitated integrated learning, promoted self-evaluation, aided adaptation to the flipped classroom and enhanced teacher-student interaction. CONCLUSIONS: Combining case-based learning, a flipped classroom and concept maps is an effective learning approach for undergraduate nursing students. It may improve students' self-directed learning, cognitive maturity and learning strategy. Additionally, concept maps are a beneficial supplement to case-based learning and a flipped classroom in terms of guiding integrated learning, promoting self-evaluation, enhancing adaptation to a flipped classroom and increasing interaction between teachers and students and between classmates.

Endoplasmic Reticulum Stress in the Pathogenesis of Hyperglycemia Induced by Thiamine-Responsive Megaloblastic Anemia.

BACKGROUND: Thiamine responsive megaloblastic anemia (TRMA) is a genetic disease caused by SLC19A2 gene mutation. This study aimed to preliminarily explore the relationship between endoplasmic reticulum stress (ERS)-PERK signaling pathway and the pathogenesis of hyperglycemia induced by TRMA. METHODS: Islet ß (INS.1 and ß-TC-6) and HEK293T cell line models with stable overexpression of SLC19A2 and SLC19A2 (c.1409insT) were established. The cells were divided into empty virus group (control), wild-type group (overexpressed SLC19A2), and mutation group (overexpressed SLC19A2 (c.1409insT)). Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and western blotting were used to detect the expression levels of ERS-PERK signaling pathway-related proteins, including glucose-regulated protein 78 (GRP78), protein kinase R-like ER kinase (PERK), and eukaryotic initiation factor 2 (eIF2α), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP) in islet ß cells. Protein localization was assessed by immunofluorescence staining. RESULTS: Compared with the control group, the mRNA expression levels of SLC19A2 in wild-type and mutant islet ß cells (INS.1 and ß-TC-6) and HEK293T cells were significantly upregulated (all p < 0.05). Compared with the control group and the wild-type group, the mRNA expression levels of GRP78, PERK, eIF2α, ATF4, and CHOP were increased (all p < 0.05) in the mutant islet ß cells; the protein expression levels of PERK, GRP78, and eIF2α were elevated (all p < 0.05). In addition, the results of immunofluorescence staining showed that SLC19A2 (c.1409insT) mutation changed the localization of the proteins in the cells. Thus, they were not located on the cell surface, but in the cytoplasm and nuclei, and protein aggregation occurred in the cytoplasm. CONCLUSIONS: 1. Islet ß and HEK293Tcell lines, stably overexpressing SLC19A2 and SLC19A2 (c.1409insT) mutations, were successfully constructed. 2. SLC19A2 (c.1409insT) mutation could raise the expression levels of ERS-PERK signaling pathway-related proteins (GRP78, PERK, eIF2α, ATF4, and CHOP), and activate apoptosis pathway. 3. SLC19A2 (c.1409insT) mutation could change the localization of proteins and produce protein aggregation in cells. It could lead to protein misfolding and ERS, which would participate in the pathological mechanism of hyperglycemia induced by TRMA.

Identification of immune-related genes and patient selection for hepatocellular carcinoma immunotherapy.

Background: Hepatocellular carcinoma (HCC) is a malignant disease with a poor prognosis. Among the treatment strategies for HCC, tumor immunotherapy (TIT) is a promising research hotspot, in which identifying novel immune-related biomarkers and selecting suitable patient population are urgent issues to be solved. Methods: In this study, an abnormal expression map of HCC cell genes was constructed using public high-throughput data from 7,384 samples (3,941 HCC vs. 3,443 non-HCC tissues). Through single-cell RNA sequencing (scRNA-seq) cell trajectory analysis, the genes defined as potential drivers of HCC cell differentiation and development were selected. By screening for both immune-related genes and those associated with high differentiation potential in HCC cell development, a series of target genes were identified. Coexpression analysis was performed using Multiscale Embedded Gene Co-expression Network Analysis (MEGENA) to find the specific candidate genes involved in similar biological processes. Subsequently, nonnegative matrix factorization (NMF) was conducted to select patients suitable for HCC immunotherapy based on the coexpression network of candidate genes. Results: HSP90AA1, CDK4, HSPA8, HSPH1, and HSPA5 were identified as promising biomarkers for prognosis prediction and immunotherapy of HCC. Through the use of our molecular classification system, which was based on a function module containing 5 candidate genes, patients with specific characteristics were found to be suitable candidates for TIT. Conclusions: These findings provide new insights into the selection of candidate biomarkers and patient populations for future HCC immunotherapy.

Effects of agricultural land types on microplastic abundance: A nationwide meta-analysis in China.

Microplastics (MPs) accumulation in agricultural land that possibly poses threats to food security and human health has recently attracted increasing attention. Land use type probably is a key factor that drives the contamination level of soil MPs. Nevertheless, few studies have performed large-scale systematic analysis of the effects in different agricultural land soils on the MPs abundance. In this study, we constructed a national MPs dataset comprising 321 observations from 28 articles, summarised the current status of microplastic pollution in five agricultural land types in China through meta-analysis, and investigated the effects and key factors of agricultural land types on microplastic abundance. The results showed that among the existing soil microplastic research, vegetable soils maintained a higher environmental exposure distribution than other agricultural lands, and with the most common trend being vegetable land > orchard land > cropland > grassland. By combining agricultural practices, demographic economic factors and geographical factors, a potential impact identification method based on subgroup analysis was established. The findings demonstrated that agricultural film mulch significantly increased soil MPs abundance, especially in orchards. Increased population and economy (carbon emissions and PM2.5 concentrations) add MPs abundance in all kinds of agricultural lands. And the significant changes of effect sizes in high-latitude and mid-altitude areas suggested that geographical space differences exerted a certain degree of impact on the soil distribution of MPs. By the proposed method, different levels of MPs risk areas in agricultural soils can be more reasonably and effectively identified, which will provide type-specific policies technical and theoretical support for the precise management of MPs in agricultural land soils.

Novel insights into the temporal molecular fractionation of dissolved black carbon at the iron oxyhydroxide - water interface.

As the most reactive and mobile fraction of black carbon, dissolved black carbon (DBC) inexorably interacts with minerals in the biosphere. Nevertheless, the research on the mechanisms and compositions of DBC assembly at the mineral-water interface remains limited. In this study, we revealed the "kinetic architecture" of DBC on iron oxyhydroxide at novel insights based on quantitative and qualitative approaches. The results indicated that high molecular weight, highly unsaturated, oxygen-rich (such as carboxyl-rich fraction, phenolics), aliphatics, and long C chains compounds were preferentially adsorbed on the iron oxyhydroxide. 2D-COS analyses directly disclosed the sequential fractionation: aromatic and phenolic groups > aliphatic groups, and few aromatics were continuously adsorbed after the rapid adsorption. Quantitative determinations identified that aromatic and phenolic components were adsorbed rapidly over the first 60 min, while aromatics achieved the dynamic equilibrium until ∼300 min, which was consistent with the 2D-COS observations. Our findings supported the hypothesis that "mineral-OM" and "OM-OM" interactions worked simultaneously, and the adsorption might be co-driven by ligand exchange, hydrophobic interactions, and other mechanisms. This work provided the theoretical basis for organic carbon storage and turnover, and it was valuable for predicting the behaviors and fates of contaminants at the soil-water interface and surface water.

Characterization of dissolved black carbon and its binding behaviors to ceftazidime and diclofenac pharmaceuticals: Employing the molecular weight fractionation.

As the ubiquitous component of the aquatic environment, dissolved organic matter (DOM) readily bind with residual pharmaceutical contaminants (PCs) and influence their environmental behaviors. However, the binding mechanisms between dissolved black carbon (DBC), a vital part of the natural DOM pool, and PCs were poorly researched. In this study, the bulk DBC was divided into four fractions in molecular weight (MW) via an ultrafiltration system, and the properties of DBC and their binding interaction with two kinds of typical PCs (ceftazidime (CAZ) and diclofenac (DCF)) were explored concretely. The results showed that low MW component was the main contributor to bulk DBC, and the aromaticity increased with the increase of MW. The categories of chemical structures and fluorescent substances in different MW DBC were similar. Multispectral techniques showed that the oxygen-enriched compounds in DBC had the higher affinity to CAZ/DCF. The -NH-, -COOH, -NH2 groups in CAZ molecules appeared to form the hydrogen bond with DBC. Fluorescence quenching experiments were analyzed, and the binding mechanisms were specifically expounded from the thermodynamic perspective. The fluorophore of fulvic acid-like compounds (FA) were quenched by both static and dynamic quenching mechanisms, while only static quenching occurred for humic acid-like compounds (HA). For bulk DBC, the hydrogen bond and van der Waals force were the major forces in the HA-CAZ system, while the hydrophobic force made the primary contribution to the HA-DCF system, which might be ascribed to the higher hydrophobic nature of DCF. Notably, with the increase of HA MW, the main binding mode of HA-CAZ/DCF changed from hydrophobic force to hydrogen bond and van der Waals force gradually, which also directly proved that various noncovalent interactions co-driven the binding processes. Our findings are beneficial to better assess the fate of DBC and PCs and the corresponding complexes in the aquatic environment.

Clinical Significance and Prognostic Value of Lactate Dehydrogenase Expression in Cervical Cancer.

Background: Lactate dehydrogenase (LDH) is a marker of injury and disease as it is expressed extensively in numerous cell types and tissues. Moreover it is released during tissue breakdown, and is elevated in cancerous tissues. However, the clinical significance and prognostic value of LDH as a tumor marker have been subject to considerable discussion. Objective: In this study, clinical serum LDH data from patients with cervical cancer (CC), CC microarray data, and RNA-seq data were integrated to assess the expression of LDH in CC. Methods: A total of 204 patients with newly diagnosed CC and 204 age-matched healthy controls were included to evaluate serum LDH levels in CC and non-cancer samples. External microarrays and RNA-seq datasets were collected for the differential expression analysis of LDH in CC and non-cancer tissue samples. Kaplan-Meier survival curves of the prognostic value of LDH for CC were plotted for RNA-seq data. Functional enrichment analysis was performed for the genes co-expressed with LDH. Results: The data from our in-house clinical cases as well as the data extracted from microarrays and RNA-seq databases demonstrated significant overexpression of LDH in CC samples. Elevated LDH expression levels were associated with poor overall survival in CC patients. The genes co-expressed with LDH were significantly correlated with the biological processes and pathways, associated with nuclear division, the condensed chromosome, protein serine/threonine kinase activity, and the cell cycle. Conclusion: In conclusion, LDH upregulation might serve as a therapeutic and prognostic biomarker for CC.

N-CQDs from reed straw enriching charge over BiO2-x/BiOCl p-n heterojunction for improved visible-light-driven photodegradation of organic pollutants.

Green bismuth-based photocatalysts have attracted extensive attention in the field of PPCPs photodegradation. The improved carrier separation efficiency still remains a key factor to enhance photocatalytic performance. Herein, N-doped biomass carbon quantum dots (N-CQDs) decorated p-n heterojunction photocatalyst BiO2-x/BiOCl was prepared using a facile ion-etching strategy, and it displayed a markedly enhanced catalytic activity in the photodegradation of sulfonamide antibiotics. Calculated by the differential charge density, the doped N-CQDs could gather photogenerated electrons, which indicated that the introduction of N-CQDs into BiO2-x/BiOCl would effectively inhibit the recombination of photogenerated charge carriers. In addition, photocatalytic performance and density functional theory (DFT) calculation results revealed that the photogenerated electrons tended to transfer from p-BiOCl to n-BiO2-x through N-CQDs, which could generate ·O2- and photogenerated h+ to oxidize the target pollutants. Benefiting from the synergistic effect of accelerated separation of e--h+ in p-n heterojunction and the electron-rich performance of N-CQDs, the superb TOC removal efficiencies (89.40% within 120 min visible-light irradiation) and toxicity reduction performance of photodegradation intermediates were achieved. As a consequence, this work will provide a design of high-quality photocatalysts and a green-promising strategy for bismuth-based photocatalysts in the water treatment of PPCPs.

Anesthetic management in cesarean delivery of women with placenta previa: a retrospective cohort study.

BACKGROUND: The incidence of placenta preiva is rising. Cesarean delivery is identified as the only safe and appropriate mode of delivery for pregnancies with placenta previa. Anesthesia is important during the cesarean delivery. The aim of this study is to assess maternal and neonatal outcomes of patients with placenta previa managed with neuraxial anesthesia as compared to those who underwent general anesthesia during cesarean delivery. METHODS: A retrospective cohort study was performed of all patients with placenta preiva at our large academic institution from January 1, 2014 to June 30, 2019. Patients were managed neuraxial anesthesia and general anesthesia during cesarean delivery. RESULTS: We identified 1234 patients with placenta previa who underwent cesarean delivery at our institution. Neuraxial anesthesia was performed in 737 (59.7%), and general anesthesia was completed in 497 (40.3%) patients. The mean estimated blood loss at neuraxial anesthesia of 558.96 ± 42.77 ml were significantly lower than the estimated blood loss at general anesthesia of 1952.51 ± 180 ml (p < 0.001). One hundred and forty-six of 737 (19.8%) patients required blood transfusion at neuraxial anesthesia, whereas 381 out of 497 (76.7%) patients required blood transfusion at general anesthesia. The rate neonatal asphyxia and admission to NICU at neuraxial anesthesia was significantly lower than general anesthesia (2.7% vs. 19.5 and 18.2% vs. 44.1%, respectively). After adjusting confounding factors, blood loss was less, Apgar score at 1- and 5-min were higher, and the rate of blood transfusion, neonatal asphyxia, and admission to NICU were lower in the neuraxial group. CONCLUSIONS: Our data demonstrated that neuraxial anesthesia is associated with better maternal and neonatal outcomes during cesarean delivery in women with placenta previa.

Hereditary spherocytosis overlooked for 7 years in a pediatric patient with ß-thalassemia trait and novel compound heterozygous mutations of SPTA1 gene.

Objectives: We aimed to determine the clinical and genetic characteristics of a boy diagnosed with the ß-thalassemia trait. He also had hereditary spherocytosis (HS) that had been overlooked for 7 years. Methods: Blood samples collected from the proband and his family were assessed by laboratory tests, and next-generation sequencing (NGS) and Sanger sequencing. Results: The ß-thalassemia trait was complicated with HS in the proband. Compound heterozygous mutations of the Spectrin Alpha, Erythrocytic 1 (SPTA1) gene, c.83G > A and c.190G > A in the proband were inherited from his mother and father, respectively, and he also had the heterozygous c.126_129delCTTT mutation in the Hemoglobin Subunit Beta (HBB) gene. The c.190G > A mutation has not yet been added to the Human Gene Mutation Database (HGMD®). The heterozygous HBB c.126_129delCTTT mutation was inherited from his mother, and his older brother also had this mutation. Conclusion: Compared with other patients with either HS or ß-thalassemia, this proband with both HS and the ß-thalassemia trait had very complicated laboratory findings, which resulted in HS being overlooked for 7 years. Genetic testing is invaluable for the differential diagnosis of hereditary anemias with overlapping clinical features.

Eliminating the Effect of Reflectance Properties on Reconstruction in Stripe Structured Light System.

The acquisition of the geometry of general scenes is related to the interplay of surface geometry, material properties and illumination characteristics. Surface texture and non-Lambertian reflectance properties degrade the reconstruction results by structured light technique. Existing structured light techniques focus on different coding strategy and light sources to improve reconstruction accuracy. The hybrid system consisting of a structured light technique and photometric stereo combines the depth value with normal information to refine the reconstruction results. In this paper, we propose a novel hybrid system consisting of stripe-based structured light and photometric stereo. The effect of surface texture and non-Lambertian reflection on stripe detection is first concluded. Contrary to existing fusion strategy, we propose an improved method for stripe detection to reduce the above factor's effects on accuracy. The reconstruction problem for general scene comes down to using reflectance properties to improve the accuracy of stripe detection. Several objects, including checkerboard, metal-flat plane and free-form objects with complex reflectance properties, were reconstructed to validate our proposed method, which illustrates the effectiveness on improving the reconstruction accuracy of complex objects. The three-step phase-shifting algorithm was implemented and the reconstruction results were given and also compared with ours. In addition, our proposed framework provides a new feasible scheme for solving the ongoing problem of the reconstruction of complex objects with variant reflectance. The problem can be solved by subtracting the non-Lambertian components from the original grey values of stripe to improve the accuracy of stripe detection. In the future, based on stripe structured light technique, more general reflection models can be used to model different types of reflection properties of complex objects.

Accurate infrared structured light sensing system for dynamic 3D acquisition.

3D real-time acquisition plays a vital role in computer graphics and computer vision. In this paper, we present a dynamic IR structured light sensing system with high resolution and accuracy for real-time 3D scanning. We adopt the Gray code combined with stripe shifting as our 3D acquisition's coding strategy and parallelize the algorithm via the GPU in our IR 3D scanning system. Our built-up system can capture dense and high-precision 3D model sequences with a speed of 29 Hz. Furthermore, we propose a practical calibration method to obtain accurate calibration parameters for our system. Finally, various experiments are performed to verify the feasibility and accuracy of our proposed IR structured light sensing system.

Enhanced removal of organic contaminants in water by the combination of peroxymonosulfate and carbonate.

In this study, a favorable CO32-/PMS system for efficient degradation of organic contaminants (acid orange 7 (AO7), acetaminophen, para-aminobenzoic acid, phenol, methylene orange, methylene blue) in water was firstly reported. Under optimal conditions, the decolorization ration of AO7 was 100% within 40 min. Data fitting showed that the AO7 decolorization could be described by the pseudo-first-order kinetics, and the rates constant values ranging from 0.0006 to 0.2297 min-1 depending on the operating parameters (initial PMS, CO32-, AO7 concentrations). Radical scavenging studies revealed that superoxide anion radical (O2-) and singlet oxygen (1O2) rather than sulfate (SO4-) nor hydroxyl (HO) were the dominant oxidants might be responsible for AO7 degradation. The presence of NO3-, HPO42- and low concentration of Cl-, NO2-, HCO3-, H2PO4-, HA had no significantly effect on the decolorization of AO7. Adding a higher Cl- concentration displayed favorable effects on the removal efficiencies of AO7, but adding a higher NO2-, HCO3-, H2PO4- and HA concentration apparently inhibited this process. The decolorization of AO7 was lower in wastewater in comparison to other natural waters and ultrapure water, which was probably due to the presence of higher concentration of colloids in wastewater. Nevertheless, up to 94.8%, 97.0% and 85.1% of AO7 were degraded from the filtrate, permeate, and retentate phases of wastewater within 60 min, respectively. Consequently, CO32-/PMS would be promising for removal methodology for AO7 in wastewater containing considerable colloids. Finally, three intermediates were identified and degradation pathways of AO7 were proposed.

Asymmetric dimethylarginine and all-cause mortality: a systematic review and meta-analysis.

Asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), impairs the beneficial effect of NO. The predictive value of ADMA for all-cause mortality remains controversial, though it is important in the development of cardiovascular disease (CVD) and progression to dialysis in renal disease. This systematic review and meta-analysis was conducted to investigate the association between circulating ADMA and all-cause mortality. Studies with data pertinent to the association between circulating ADMA and all-cause mortality were reviewed and OR, HR or RR with 95% CI derived from multivariate Cox's proportional-hazards analysis were extracted. A total of 34 studies reporting 39137 participants were included in final analysis. The results demonstrated that circulating ADMA was independently associated with all-cause mortality (RR = 1.27, 95% CI: 1.20-1.34). The association was still statistically significant in patients with pre-existing renal disease (RR = 1.30, 95% CI: 1.19-1.43) and pre-existing CVD (RR = 1.26, 95% CI: 1.16-1.37). In those without pre-existing renal or CVD, ADMA also predicted all-cause mortality (RR = 1.31, 95% CI: 1.13-1.53). The present study suggests a positive association of circulating ADMA with all-cause mortality. Further studies are needed to investigate the effects of interventions on ADMA, and the value of ADMA as a biomarker.

PDL1 Regulation by p53 via miR-34.

BACKGROUND: Although clinical studies have shown promise for targeting PD1/PDL1 signaling in non-small cell lung cancer (NSCLC), the regulation of PDL1 expression is poorly understood. Here, we show that PDL1 is regulated by p53 via miR-34. METHODS: p53 wild-type and p53-deficient cell lines (p53(-/-) and p53(+/+) HCT116, p53-inducible H1299, and p53-knockdown H460) were used to determine if p53 regulates PDL1 via miR-34. PDL1 and miR-34a expression were analyzed in samples from patients with NSCLC and mutated p53 vs wild-type p53 tumors from The Cancer Genome Atlas for Lung Adenocarcinoma (TCGA LUAD). We confirmed that PDL1 is a direct target of miR-34 with western blotting and luciferase assays and used a p53(R172HΔ)g/+K-ras(LA1/+) syngeneic mouse model (n = 12) to deliver miR-34a-loaded liposomes (MRX34) plus radiotherapy (XRT) and assessed PDL1 expression and tumor-infiltrating lymphocytes (TILs). A two-sided t test was applied to compare the mean between different treatments. RESULTS: We found that p53 regulates PDL1 via miR-34, which directly binds to the PDL1 3' untranslated region in models of NSCLC (fold-change luciferase activity to control group, mean for miR-34a = 0.50, SD = 0.2, P < .001; mean for miR-34b = 0.52, SD = 0.2, P = .006; and mean for miR-34c = 0.59, SD = 0.14, and P = .006). Therapeutic delivery of MRX34, currently the subject of a phase I clinical trial, promoted TILs (mean of CD8 expression percentage of control group = 22.5%, SD = 1.9%; mean of CD8 expression percentage of MRX34 = 30.1%, SD = 3.7%, P = .016, n = 4) and reduced CD8(+)PD1(+) cells in vivo (mean of CD8/PD1 expression percentage of control group = 40.2%, SD = 6.2%; mean of CD8/PD1 expression percentage of MRX34 = 20.3%, SD = 5.1%, P = .001, n = 4). Further, MRX34 plus XRT increased CD8(+) cell numbers more than either therapy alone (mean of CD8 expression percentage of MRX34 plus XRT to control group = 44.2%, SD = 8.7%, P = .004, n = 4). Finally, miR-34a delivery reduced the numbers of radiation-induced macrophages (mean of F4-80 expression percentage of control group = 52.4%, SD = 1.7%; mean of F4-80 expression percentage of MRX34 = 40.1%, SD = 3.5%, P = .008, n = 4) and T-regulatory cells. CONCLUSIONS: We identified a novel mechanism by which tumor immune evasion is regulated by p53/miR-34/PDL1 axis. Our results suggest that delivery of miRNAs with standard therapies, such as XRT, may represent a novel therapeutic approach for lung cancer.

miR-155 and miR-31 are differentially expressed in breast cancer patients and are correlated with the estrogen receptor and progesterone receptor status.

The purpose of the present study was to determine the tissue and plasma levels of microRNA (miR)-155 and miR-31 in 67 patients with invasive intraductal breast cancer and their correlation with the clinicopathological characteristics. Using a quantitative real-time-PCR (qRT-PCR) assay, it was demonstrated that the plasma levels of miR-155 and miR-31 in patients were 6- and 5-fold higher than those in healthy individuals, respectively (P<0.05). In cancerous tissues, miR-155 expression levels were 5-fold higher compared with those in non-cancerous tissues (P<0.05), whereas no difference was observed with miR-31 expression (P>0.05). The expression levels of miR-155, but not miR-31, were inversely correlated with estrogen receptor (ER) and progesterone receptor (PR) expression (ER, r=-0.353, P=0.003; PR, r=-0.357, P=0.003). The tissue and plasma levels of miR-155 and miR-31 were not correlated with epidermal growth factor receptor-2 (HER-2) expression levels. Furthermore, high levels of plasma miR-155 and miR-31 were identified in the tumors of TNM stage II, lymph node metastasis 0-3 and tumor sizes of 2-5 cm in patients who were aged over 52 years. miR-155 was mainly expressed in patients with a pathology score of 3 for ER or PR expression; miR-31 expression was higher in patients with a pathology score of 2. These results suggest that miR-155 and miR-31 are differentially expressed in breast cancer patients. Their correlation with the clinicopathological characteristics may aid the diagnosis and treatment of invasive intraductal breast cancer.