LARS1 is a Prognostic Biomarker and Exhibits a Correlation with Immune Infiltrates in Hepatocellular Carcinoma.

Purpose: To study the relationship between LARS1 expression and immune infiltration and prognosis in hepatocellular carcinoma (HCC). Patients and Methods: The clinical characteristics together with LARS1 expression levels were obtained from the TCGA database. Immunohistochemistry confirmed LARS1 expression levels in paraneoplastic and tumor tissues. To investigate LARS1-related downstream molecules, a network of protein-protein interactions (PPIs) and the Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) were built. Furthermore, gene set enrichment analysis (GSEA) was used to analyze the pathways associated with LARS1 expression, whereas Single-sample GSEA (ssGSEA) was applied to perform an association study between immune infiltration and LARS1 gene expression. The TISCH Database and the TISIDB database were used to compare the difference of LARS1 expression in hepatocellular carcinoma and immunomodulators. Results: In comparison to that in normal tissues, the LARS1 expression level was elevated in tumor tissues. LARS1 expression exhibited substantial correlation with AFP, Histologic grade, pathologic stage, Residual tumor, and Vascular invasion in HCC. Higher LARS1 expression in HCC was linked to lower progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS). According to the GO/KEGG study, the important biological process (neutral lipid metabolic process), cellular component (triglyceride-rich plasma lipoprotein), molecular functions (lipase inhibitor activity), and KEGG pathway (cholesterol metabolism) could be a probable function mechanism in promoting HCC. Various pathways as per GSEA revealed that they were enriched in samples with elevated LARS1 expression. The expression level of LARS1 in malignant tumor cells after immunotherapy was significantly higher than that before immunotherapy. LARS1 was also remarkably linked to the infiltration level and the immunomodulators. Conclusion: LARS1 can be used as a biomarker of HCC, which is associated to immune infiltration of HCC.

Assisted reproductive technology treatment failure and the detection of intrauterine HPV through spent embryo transfer media sample.

Cervical human papillomavirus (HPV) infection is believed to increase the risks of pregnancy failure and abortion, however, whether the uterine cavity HPV infection reduces pregnancy rate or increases miscarriage rate remains unclarified in infertile women undergoing assisted reproductive technology (ART) treatment. Therefore, we aimed to assess ART outcomes in the presence of intrauterine HPV. This was a hospital-based multicenter (five reproductive medicine centers) matched cohort study. This study involved 4153 infertile women undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection treatment in five reproductive medicine centers between October 2018 and 2020. The spent embryo transfer media sample with endometrium tissue were collected and performed with flow-through hybridization and gene chips to detect HPV DNA. According to basic characteristics, HPV-positive and negative patients were matched in a ratio of 1:4 by age, body mass index transfer timing, transfer type, and number of embryos transferred. The primary outcome was pregnancy and clinical miscarriage rates in the transfer cycle underwent HPV detection. 92 HPV-positive and 368 HPV-negative patients were screened and analyzed statistically. Univariate analysis showed uterine cavity HPV infection resulted in lower rates of ongoing pregnancy (31.5% vs. 44.6%; p = 0.023), implantation (32.3% vs. 43.1%; p = 0.026), biochemical pregnancy (47.8% vs. 62.5%; p = 0.010), and clinical pregnancy (40.2% vs. 54.3%; p = 0.015) compared with HPV negative group. The infertile female with positive HPV also had a slightly higher frequency of biochemical miscarriage (15.9% vs. 13.0%; p = 0.610) and clinical miscarriage (24.3% vs. 15.5%; p = 0.188). These findings suggest that HPV infection in the uterine cavity is a high risk for ART failure. HPV screening is recommended before ART treatment, which may be benefit to improving pregnancy outcome.

The GRHL3-regulated long non-coding RNA lnc-DC modulates keratinocytes differentiation by interacting with IGF2BP2 and up-regulating ZNF750.

BACKGROUND: Aberrant keratinocytes differentiation has been demonstrated to be associated with a number of skin diseases. The roles of lncRNAs in keratinocytes differentiation remain to be largely unknown. OBJECTIVE: Here we aim to investigate the role of lnc-DC in regulating epidermal keratinocytes differentiation. METHODS: Expression of lnc-DC in the skin was queried in AnnoLnc and verified by FISH. The lncRNA expression profiles during keratinocytes differentiation were reanalyzed and verified by qPCR and FISH. Gene knock-down and over-expression were used to explore the role of lnc-DC in keratinocytes differentiation. The downstream target of lnc-DC was screened by whole transcriptome sequencing. CUT&RUN assay and siRNAs transfection was used to reveal the regulatory effect of GRHL3 on lnc-DC. The mechanism of lnc-DC regulating ZNF750 was revealed by RIP assay and RNA stability assay. RESULTS: Lnc-DC was biasedly expressed in skin and up-regulated during epidermal keratinocytes differentiation. Knockdown lnc-DC repressed epidermal keratinocytes differentiation while over-express lnc-DC showed the opposite effect. GRHL3, a well-known transcription factor regulating keratinocytes differentiation, could bind to the promoter of lnc-DC and regulate its expression. By whole transcriptome sequencing, we identified that ZNF750 was a downstream target of lnc-DC during keratinocytes differentiation. Mechanistically, lnc-DC interacted with RNA binding protein IGF2BP2 to stabilize ZNF750 mRNA and up- regulated its downstream targets TINCR and KLF4. CONCLUSION: Our study revealed the novel role of GRHL3/lnc-DC/ZNF750 axis in regulating epidermal keratinocytes differentiation, which may provide new therapeutic targets of aberrant keratinocytes differentiation related skin diseases.

Larger hydroxyapatite aggregation from Ca2+ adhesion in ANAMMOX granular sludge caused by high dissolved oxygen.

Anaerobic ammonia oxidation (ANAMMOX), a sustainable biological process, is promising to remove NH4+-N from municipal sewage. In this study, results showed that the anammox granular sludge morphology changes with the alternation of dissolved oxygen (DO), mainly attributing to the adhesion of calcium ions (Ca2+) to the surface of sludge particles. Diverse characterization methods revealed that gray adhesions in the form of hydroxyapatite covered the original holes on the anammox granular sludge surface, including scanning Electron Microscopy (SEM), digital camera images, Energy Dispersive Spectrometer (EDS), and X-ray diffraction (XRD). Ex-situ degradation of NH4+-N and NO2--N yielded diverse outcomes. The protein to polysaccharide ratio (PN/PS) in the total extracellular polymeric substances (EPS) across 4 size groups demonstrated a decrease under O2 exposure. Microbial community analysis indicated norank_f_A4b and Nitrolancea being the most abundant genus under O2 exposure at day 1 and day 100, respectively. These findings offer an effective strategy to prevent size-larger granular sludge from deteriorating through changing DO and Ca2+ in municipal wastewater in ANAMMOX.

Tourmaline mediated enhanced autotrophic denitrification: The mechanisms of electron transfer and Paracoccus enrichment.

Autotrophic denitrification (AD) without carbon source is an inevitable choice for denitrification of municipal wastewater under the carbon peaking and carbon neutrality goals. This study first employed sulfur-tourmaline-AD (STAD) as an innovative nitrate removal trial technique in wastewater. STAD demonstrated a 2.23-fold increase in nitrate­nitrogen (NO3--N) removal rate with reduced nitrite­nitrogen (NO2--N) accumulation, effectively removing 99 % of nitrogen pollutants compared to sulfur denitrification. Some denitrifiers microorganisms that could secrete tyrosine, tryptophan, and aromatic protein (extracellular polymeric substances (EPS)). Moreover, according to the EPS composition and characteristics analysis, the secretion of loosely bound extracellular polymeric substances (LB-EPS) that bound to the bacterial endogenous respiration and enriched microbial abundance, was produced more in the STAD system, further improving the system stability. Furthermore, the addition of tourmaline (Tm) facilitated the discovery of a new genus (Paracoccus) that enhanced nitrate decomposition. Applying optimal electron donors through metabolic pathways and the microbial community helps to strengthen the AD process and treat low carbon/nitrogen ratio wastewater efficiently.

B2M is a Biomarker Associated With Immune Infiltration In High Altitude Pulmonary Edema.

BACKGROUND: High altitude pulmonary edema (HAPE) is a serious mountain sickness with certain mortality. Its early diagnosis is very important. However, the mechanism of its onset and progression is still controversial. AIM: This study aimed to analyze the HAPE occurrence and development mechanism and search for prospective biomarkers in peripheral blood. METHODS: The difference genes (DEGs) of the Control group and the HAPE group were enriched by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and then GSEA analysis was performed. After identifying the immune-related hub genes, QPCR was used to verify and analyze the hub gene function and diagnostic value with single-gene GSEA and ROC curves, and the drugs that acted on the hub gene was found in the CTD database. Immune infiltration and its association with the hub genes were analyzed using CIBERSORT. Finally, WGCNA was employed to investigate immune invasion cells' significantly related gene modules, following enrichment analysis of their GO and KEGG. RESULTS: The dataset enrichment analysis, immune invasion analysis and WGCNA analysis showed that the occurrence and early progression of HAPE were unrelated to inflammation. The hub genes associated with immunity obtained with MCODE algorithm of Cytoscape were JAK2 and B2M.. RT-qPCR and ROC curves confirmed that the hub gene B2M was a specific biomarker of HAPE and had diagnostic value, and single-gene GSEA analysis confirmed that it participated in MHC I molecule-mediated antigen presentation ability decreased, resulting in reduced immunity. CONCLUSION: Occurrence and early progression of high altitude pulmonary edema may not be related to inflammation. B2M may be a new clinical potential biomarker for HAPE for early diagnosis and therapeutic evaluation as well as therapeutic targets, and its decrease may be related to reduced immunity due to reduced ability of MCH I to participate in antigen submission.

Five-year outcomes of immediate implant placement for mandibular molars with and without chronic apical periodontitis: A retrospective study.

BACKGROUND: Most physicians consider molars with chronic apical periodontitis (CAP) lesions as contraindications for immediate implant placement. At the patient's request, we perform immediate implant placement of the mandibular molars with CAP in clinical practice. AIM: To retrospectively analyze and compare the 5-year outcomes of immediate implant placement of the mandibular molars with CAP and those without obvious inflammation. METHODS: The clinical data of patients with immediate implant placement of the mandibular molars in the Department of Oral and Maxillofacial Surgery, the Affiliated Hospital of Qingdao University, from June 2015 to June 2017 were collected. The patients were divided into CAP (n = 52) and no-CAP (n = 45) groups. Changes in bone mineral density and bone mass around implants were analyzed 5 years after implant restoration. RESULTS: At 5 years after implantation, the peri-implant bone mineral density was 528.2 ± 78.8 Hounsfield unit (HU) in the CAP group and 562.6 ± 82.9 HU in the no-CAP group (P = 0.126). Marginal bone resorption around implants did not differ significantly between the two groups, including buccal (P = 0.268) or lingual (P = 0.526) resorption in the vertical direction or buccal (P = 0.428) or lingual (P = 0.560) resorption in the horizontal direction. Changes in the peri-implant jump space did not differ significantly between the two groups, including the buccal (P = 0.247) or lingual (P = 0.604) space in the vertical direction or buccal (P = 0.527) or lingual (P = 0.707) space in the horizontal direction. The gray value of cone-beam computed tomography measured using Image J software can reflect the bone mineral density. In the CAP area, the gray values of the bone tissue immediately and 5 years after implant placement differed significantly from those of the surrounding bone tissue (P < 0.01). CONCLUSION: The results of this study suggest that immediate implant placement of the mandibular molars with CAP can achieve satisfactory 5-year clinical results, without significant differences in the complications, survival rate, or bone tissue condition from the no-CAP mandibular molars.

PHAM-YOLO: A Parallel Hybrid Attention Mechanism Network for Defect Detection of Meter in Substation.

Accurate detection and timely treatment of component defects in substations is an important measure to ensure the safe operation of power systems. In this study, taking substation meters as an example, a dataset of common meter defects, such as a fuzzy or damaged dial on the meter and broken meter housing, is constructed from the images of manual inspection in power systems. There are several challenges involved in accurately detecting defects in substation meter images, such as the complex background, different meter sizes and large differences in the shapes of meter defects. Therefore, this paper proposes the PHAM-YOLO (Parallel Hybrid Attention Mechanism You Only Look Once) network for automatic detection of substation meter defects. In order to make the network pay attention to the key areas against the complex background of the meter defect images and the differences between different defect features, a Parallel Hybrid Attention Mechanism (PHAM) module is designed and added to the backbone of YOLOv5. PHAM integration of local and non-local correlation information can highlight these differences while remaining focused on the meter defect features. To improve the expressive ability of the feature map, a Spatial Pyramid Pooling Fast (SPPF) module is introduced, which pools the input feature map using a continuous fixed convolution kernel, fusing the feature maps of different receptive fields. Bounding box regression (BBR) is the key way to determine object positioning performance in defect detection. EIOU (Efficient Intersection over Union) is, therefore, introduced as a boundary loss function to solve the ambiguity of the CIOU (Complete Intersection Over Union) loss function, making the BBR regression more accurate. The experimental results show that the Average Precision Mean (mAP), Precision (P) and Recall (R) of the proposed PHAM-YOLO network in the dataset are 78.3%, 78.3%, and 79.9%, respectively, with mAP being improved by 2.7% compared to the original model and higher than SSD, Fast R-CNN, etc.

MLink: Linking Black-Box Models From Multiple Domains for Collaborative Inference.

The cost efficiency of model inference is critical to real-world machine learning (ML) applications, especially for delay-sensitive tasks and resource-limited devices. A typical dilemma is: in order to provide complex intelligent services (e.g., smart city), we need inference results of multiple ML models, but the cost budget (e.g., GPU memory) is not enough to run all of them. In this work, we study underlying relationships among black-box ML models and propose a novel learning task: model linking, which aims to bridge the knowledge of different black-box models by learning mappings (dubbed model links) between their output spaces. We propose the design of model links which supports linking heterogeneous black-box ML models. Also, in order to address the distribution discrepancy challenge, we present adaptation and aggregation methods of model links. Based on our proposed model links, we developed a scheduling algorithm, named MLink. Through collaborative multi-model inference enabled by model links, MLink can improve the accuracy of obtained inference results under the cost budget. We evaluated MLink on a multi-modal dataset with seven different ML models and two real-world video analytics systems with six ML models and 3,264 hours of video. Experimental results show that our proposed model links can be effectively built among various black-box models. Under the budget of GPU memory, MLink can save 66.7% inference computations while preserving 94% inference accuracy, which outperforms multi-task learning, deep reinforcement learning-based scheduler and frame filtering baselines.

Development of an artificial intelligence based model for predicting the euploidy of blastocysts in PGT-A treatments.

The euploidy of embryos is unpredictable before transfer in in vitro fertilisation (IVF) treatments without pre-implantation genetic testing (PGT). Previous studies have suggested that morphokinetic characteristics using an artificial intelligence (AI)-based model in the time-lapse monitoring (TLM) system were correlated with the outcomes of frozen embryo transfer (FET), but the predictive effectiveness of the model for euploidy remains to be perfected. In this study, we combined morphokinetic characteristics, morphological characteristics of blastocysts, and clinical parameters of patients to build a model to predict the euploidy of blastocysts and live births in PGT for aneuploidy treatments. The model was effective in predicting euploidy (AUC = 0.879) but was ineffective in predicting live birth after FET. These results provide a potential method for the selection of embryos for IVF treatments with non-PGT.

The Role of Al4C3 Morphology in Tensile Properties of Carbon Fiber Reinforced 2024 Aluminum Alloy during Thermal Exposure.

The aluminum alloy drill pipe suffers long-term high-temperature conditions during ultra-deep well drilling. In this paper, the samples were prepared by vacuum hot pressing, followed by hot extrusion and T6 heat treatment. The mechanical properties of short carbon fiber reinforced 2024 aluminum alloy composites (SCFs/2024 Al) and the microstructure evolution at the interface region thermal exposure at 160 °C for 500 h are discussed. The experimental results showed that the effect of short carbon fiber on 2024 aluminum alloy remained steady throughout the whole process of the heat exposure experiment. The distribution and volume of interface products (Al4C3) changed with the prolonging of heat exposure time, and connected after coarsening. The evolution of the morphology of Al4C3 relieved the stress of the interface between carbon fiber and aluminum alloy matrix and enhanced the mechanical properties of the composite.

Ovarian stimulation in IVF couples with severe male factor infertility: GnRH antagonist versus long GnRH agonist.

Objective: To examine the efficacy of gonadotropin releasing hormone (GnRH) antagonist (GnRH-ant) protocol and the long GnRH agonist (GnRH-a) protocol during in vitro fertilization (IVF) therapy in patients with severe male infertile factors. Methods: A total of 983 women with severe male factor infertility undergoing IVF therapy from 2017 to 2020 at one center were retrospectively analyzed. Patients were divided into the GnRH-ant group (n=527) and the GnRH-a group (n=456) according to their ovarian stimulation protocols. Patient baseline characteristics, ovarian stimulation characteristics, and clinical pregnancy outcomes were compared between the groups. The live birth rate was considered the main pregnancy outcome. Results: GnRH-a group had a higher live birth rate compared with the GnRH-ant group (41.0% versus 31.3%, p=0.002). Moreover, the implantation (32.8% vs. 28.1%, p=0.033), biochemical pregnancy (52.4% versus 44.8%, p=0.017), clinical pregnancy (49.3% versus 39.7%, p=0.002) and ongoing pregnancy rates (43.2% vs. 34.9%, p=0.008) were higher in GnRH-a group. For patients with one embryo transferred, the GnRH-a group demonstrated higher live birth (37.0% vs. 19.4%, p=0.010) and ongoing pregnancy rate (38.9% vs. 24.5%, p=0.046) than the GnRH-ant group. Among patients with two embryos transferred, the live birth rate was also higher in the GnRH-a group than in the GnRH-ant group, with no statistical difference. No significant differences were observed in the biochemical abortion rate, clinical miscarriage rate, early miscarriage rate, late miscarriage rate, heterotopic pregnancy rate, twin pregnancy rate, and birth sex ratio between the two groups. Conclusion: For individuals with severe male infertility undergoing IVF, the GnRH-a protocol is considered a more efficient and feasible strategy with a higher live birth rate compared to the GnRH-ant protocol, especially in single embryo transfer.

Detection of Tomato Ringspot Virus Based on Microfluidic Impedance Sensor.

A microfluidic impedance sensor embedded with gold interdigitated array microelectrodes was utilized to rapidly detect Tomato Ringspot Virus (ToRSV) and achieve efficient and precise detection. The electrochemical impedance spectrum was obtained by immobilizing ToRSV antibody on the surface of a gold interdigital array microelectrode and mixing it with ToRSV to generate an impedance change. The electrochemical impedance spectrum was obtained. The equivalent circuit was established to analyze the mechanism of impedance change, and the quantitative linear relationship between ToRSV concentration and impedance was established. According to an equivalent circuit analysis, ToRSV increases the solution resistance Rs, the electron transfer resistance Ret on the electrode surface, and the double layer capacitance Cdl, resulting in an increase in impedance. The results reveal that the ToRSV concentration detected in the range of 0.001 to 10 µg/mL ranges from 248.8 to 687.2 kΩ at the ideal detection frequency of 10.7 Hz, with a good linear connection, R2 = 0.98. When this method's detection limit is tested, the impedance value is 367.68 kΩ. 0.0032 µg/mL was the detection limit. The sensor is quick and easy to use, has high detection sensitivity, and can be used to detect other plant viruses.

Study on the Motion Characteristics of Solid Particles in Fine Flow Channels by Ultrasonic Cavitation.

Microjets caused by the cavitation effect in microchannels can affect the motion trajectory of solid particles in microchannels under ultrasonic conditions. The optimal parameters for an observation experiment were obtained through simulations, and an experiment was designed to verify these parameters. When the cavitation bubbles collapse in the near-wall area, the solid particles in the microchannel can be displaced along the expected motion trajectory. Using fluent software to simulate the bubble collapse process, it can be seen that, when an ultrasonic sound pressure acts on a bubble near the wall, the pressure causes the top of the bubble wall to sink inward and eventually penetrate the bottom of the bubble wall, forming a high-speed microjet. The maximum speed of the jet can reach nearly 28 m/s, and the liquid near the top of the bubble also moves at a high speed, driving the particles in the liquid towards the wall. A high-speed camera was used to observe the ultrasonic cavitation process of bubbles in the water to verify the simulation results. A comparison of particle motion with and without ultrasonic waves proved the feasibility of using the ultrasonic cavitation effect to guide small particles towards the wall. This method provides a novel experimental basis for changing the fluid layer state in the microchannel and improving precision machining.

Vector analysis of Contoura Vision for the correction of myopia and myopic astigmatism.

AIM: To evaluate the visual outcomes of Contoura Vision (CV) with automatic eye tracking system in eyes with myopia and myopic astigmatism. METHODS: This prospective study included 160 eyes (80 patients) with moderate myopia and irregular astigmatism between January and August 2018. Subjects were randomly divided into CV group (80 eyes) that underwent CV femtosecond laser-assisted in situ keratomileusis (FS-LASIK) and a control group (80 eyes) that underwent wavefront-optimized FS-LASIK. Visual outcomes and astigmatic vector analysis were evaluated and compared between preoperatively and 3mo postoperatively. RESULTS: Basic details were similar in both groups (P>0.05). At 3mo postoperatively, uncorrected distance visual acuity was 20/16, 20/20, and 20/25 in 24, 76, and 80 eyes of patients in CV group, respectively. The CV group was better in predictability of astigmatism correction at 3mo postoperatively. In CV group, 64 eyes had deviation of astigmatic axis within 15° and 28 eyes had deviation of astigmatic axis within 5°, both were better than those in the control group. The number of eyes with residual astigmatism within 0.5 D were less in CV group (48 eyes) than the control group (40 eyes). Compared with the preoperative, C7 significantly reduced to 0.056±0.030 in CV group at 3mo after the procedure (P<0.05), and were significantly lower than those in the control group (P<0.05). CONCLUSION: CV with automatic eye tracking system is safe and effective for the correction of myopia and myopic astigmatism.

Single medium-sized hepatocellular carcinoma treated with sequential conventional transarterial chemoembolization (cTACE) and microwave ablation at 4 weeks versus cTACE alone: a propensity score.

BACKGROUND: Microwave ablation (MWA) is a potentially curative treatment for unresectable patients with hepatocellular carcinoma (HCC) ≤ 3 cm, while its therapeutic efficacy decreases significantly for HCC > 3cm. Previous studies have demonstrated that conventional transarterial chemoembolization (cTACE) combined with MWA (cTACE-MWA) may improve local tumor control rate and reduce the recurrence rate for HCC > 3cm. However, there have been few study designs to analyze the clinical efficacy of cTACE-MWA for medium-sized HCC (3-5cm). Therefore, this study aims to compare the clinical efficacy and safety of cTACE-MWA with cTACE alone for a single medium-sized HCC of 3-5 cm in diameter. METHODS: We retrospectively investigate the data of 90 patients with a single medium-sized HCC who were referred to our hospital and underwent cTACE-MWA or cTACE alone from December 2017 to March 2020. Then, patients were identified with propensity score-matched (1:1). The local tumor response to treatment and time to progression (TTP) were compared using mRECIST criteria between the cTACE-MWA group and the cTACE group. RESULTS: A total of 42 patients were included after matching (cTACE-MWA: 21; cTACE: 21). Comparing with cTACE, cTACE-MWA demonstrate significantly better local tumor control (ORR: 95.2% vs 61.9%, p = 0.02; DCR: 95.2% vs 66.7%, p = 0.045) and TTP (median 19.8 months vs 6.8 months, p < 0.001). The 1- and 2-year cumulative probabilities of OS were 100% and 95% in the cTACE-MWA group, which were significantly higher than those in the cTACE group (95% and 76%) (p = 0.032). Multivariate Cox regression analysis illustrates that cTACE-MWA was associated with better TTP (hazard ratio, 0.28; 95% CI: 0.1, 0.76; p = 0.012), but tumor size was associated with worse TTP (hazard ratio, 1.71; 95% CI: 1.01, 2.89; p = 0.045). CONCLUSIONS: cTACE followed by MWA improved TTP and OS in patients with a single medium-sized HCC, and no major complication was observed in this study.

Integrated Bioinformatics Analysis for Identifying the Significant Genes as Poor Prognostic Markers in Gastric Adenocarcinoma.

Gastric adenocarcinoma (GAC) is the most common histological type of gastric cancer and imposes a considerable health burden globally. The purpose of this study was to identify significant genes and key pathways participated in the initiation and progression of GAC. Four datasets (GSE13911, GSE19826, GSE54129, and GSE79973) including 171 GAC and 77 normal tissues from Gene Expression Omnibus (GEO) database were collected and analyzed. Through integrated bioinformatics analysis, we obtained 69 commonly differentially expressed genes (DEGs) among the four datasets, including 20 upregulated and 49 downregulated genes. The prime module in protein-protein interaction network of DEGs, including ADAMTS2, COL10A1, COL1A1, COL1A2, COL8A1, BGN, and SPP1, was enriched in protein digestion and absorption, ECM-receptor interaction, focal adhesion, PI3K-Akt signaling pathway, and amoebiasis. Furthermore, expression and survival analysis found that all seven hub genes were highly expressed in GAC tissues and 6 of them (except for SPP1) were able to predict poor prognosis of GAC. Finally, we verified the 6 high-expressed hub genes in GAC tissues via immunohistochemistry, Western blot, and RNA quantification analysis. Altogether, we identified six significantly upregulated DEGs as poor prognostic markers in GAC based on integrated bioinformatical methods, which could be potential molecular markers and therapeutic targets for GAC patients.

Identification of significant genes as prognostic markers and potential tumor suppressors in lung adenocarcinoma via bioinformatical analysis.

BACKGROUND: Lung adenocarcinoma (LAC) is the predominant histologic subtype of lung cancer and has a complicated pathogenesis with high mortality. The purpose of this study was to identify differentially expressed genes (DEGs) with prognostic value and determine their underlying mechanisms. METHODS: Gene expression data of GSE27262 and GSE118370 were acquired from the Gene Expression Omnibus database, enrolling 31 LAC and 31 normal tissues. Common DEGs between LAC and normal tissues were identified using the GEO2R tool and Venn diagram software. Next, the Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used to analyze the Gene Ontology and Kyoto Encyclopedia of Gene and Genome (KEGG) pathways. Then, protein-protein interaction (PPI) network of DEGs was visualized by Cytoscape with Search Tool for the Retrieval of Interacting Genes and central genes were identified via Molecular Complex Detection. Furthermore, the expression and prognostic information of central genes were validated via Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan-Meier analysis, respectively. Finally, DAVID, real-time PCR and immunohistochemistry were applied to re-analyze the identified genes, which were also further validated in two additional datasets from ArrayExpress database. RESULTS: First, 189 common DEGs were identified among the two datasets, including 162 downregulated and 27 upregulated genes. Next, Gene Ontology and KEGG pathway analysis of the DEGs were conducted through DAVID. Then, PPI network of DEGs was constructed and 17 downregulated central genes were identified. Furthermore, the 17 downregulated central genes were validated via GEPIA and datasets from ArrayExpress, and 12 of them showed a significantly better prognosis. Finally, six genes were identified significantly enriched in neuroactive ligand-receptor interactions (EDNRB, RXFP1, P2RY1, CALCRL) and Rap1 signaling pathway (TEK, P2RY1, ANGPT1) via DAVID, which were further validated to be weakly expressed in LAC tissues via RNA quantification and immunohistochemistry analysis. CONCLUSIONS: The low expression pattern and relation to prognosis indicated that the six genes were potential tumor suppressor genes in LAC. In conclusion, we identified six significantly downregulated DEGs as prognostic markers and potential tumor suppressor genes in LAC based on integrated bioinformatics methods, which could act as potential molecular markers and therapeutic targets for LAC patients.

HDAC2 inhibits EMT-mediated cancer metastasis by downregulating the long noncoding RNA H19 in colorectal cancer.

BACKGROUND: Emerging evidence suggests that epithelial mesenchymal transition (EMT) and epigenetic mechanisms promote metastasis. Histone deacetylases (HDACs) and noncoding RNAs (ncRNAs) are important epigenetic regulators. Here, we elucidated a novel role of histone deacetylase 2 (HDAC2) in regulating EMT and CRC metastasis via ncRNA. METHODS: The expression of HDACs in CRC was analyzed using the public databases and matched primary and metastatic tissues, and CRC cells with different metastatic potentials (DLD1, HCT116, SW480 and SW620). Microarray analysis was used to identify differential genes in parental and HDAC2 knockout CRC cells. EMT and histone modifications were determined using western blot and immunofluorescence. Migration ability was assessed by transwell assay, and metastasis was assessed in vivo using a tail vain injection. Gene expression and regulation was assessed by RT-PCR, chromatin immunoprecipitation and reporter assays. Protein interaction was assessed by immunoprecipitation. Specific siRNAs targeting H19, SP1 and MMP14 were used to validate their role in HDAC2 loss induced EMT and metastasis. RESULTS: Reduced HDAC2 expression was associated with poor prognosis in CRC patients and found in CRC metastasis. HDAC2 deletion or knockdown induced EMT and metastasis by upregulating the long noncoding RNA H19 (LncRNA H19). HDAC2 inhibited LncRNA H19 expression by histone H3K27 deacetylation in its promoter via binding with SP1. LncRNA H19 functioned as a miR-22-3P sponge to increase the expression of MMP14. HDAC2 loss strongly promoted CRC lung metastasis, which was suppressed LncRNA H19 knockdown. CONCLUSION: Our study supports HDAC2 as a CRC metastasis suppressor through the inhibition of EMT and the expression of H19 and MMP14.

Urinary bisphenol A concentration is correlated with poorer oocyte retrieval and embryo implantation outcomes in patients with tubal factor infertility undergoing in vitro fertilisation.

Bisphenol A (BPA) is a substance ubiquitously present in the environment, and its toxicity on reproductive function has been well characterised in animal models. However, it is still controversy about the effects of BPA exposure on human female reproduction. Therefore, in the present study, the associations of urinary BPA concentration with the outcomes of in vitro fertilisation (IVF) and embryo transfer from fresh and frozen cycles were analysed in the same cohort. 351 women who underwent IVF treatment from September 2013 to October 2016, at the Centre of Reproductive Medicine in the Women's Hospital School of Medicine at Zhejiang University were recruited. Single-spot urine samples were collected on the day of oocyte retrieval to detect BPA using solid-phase extraction and liquid chromatography coupled with tandem mass spectrometry. A multivariable generalised linear mixed model was used to evaluate the association between the urinary BPA concentration and IVF outcomes. After adjustment for age, body mass index, baseline follicle-stimulating hormone level, baseline oestradiol level, and antral follicle count, a significant decrease in the number of retrieved oocytes and in the rates of clinical pregnancy and implantation was observed in the patients with a high urinary BPA concentration. We concluded that BPA exposure exert negative effects on oocyte retrieval and embryo implantation in women undergoing IVF.