3D FRP Reinforcement Systems for Concrete Beams: Innovation towards High Performance Concrete Structures.

Despite the advantages of using lightweight and non-corrosive carbon fiber reinforced polymer (CFRP) reinforcements in concrete structures, their widespread adoption has been limited due to concerns regarding the brittle failure of CFRP rupture and its relatively softer load-deflection stiffness. This work offers logical solutions to these two crucial problems: using aggregate coating to strengthen the CFRP-concrete bond and ultimately the load-deflection stiffness, and using CFRP-concrete debonding propagation to create pseudo-ductile behavior. Subsequently, the concrete cracking behavior, the apparent CFRP modulus with aggregates, and the post-peak capacity and deflection of three-dimensional (3D) CFRP-reinforced concrete are all described by equations derived from experiments. These formulas will be helpful in the future design of non-prismatic concrete components for low-impact building projects. The potential of this innovative design scheme in terms of increased capacity and deflections with less concrete material is demonstrated through comparisons between non-prismatic CFRP-reinforced concrete and measured steel reinforced equivalency.

Dehydroabietylamine exerts antitumor effects by affecting nucleotide metabolism in gastric cancer.

Nucleotide metabolism is the ultimate and most critical link in the self-replication process of tumors, including gastric cancer (GC). However, in clinical treatment, classic anti-tumor drugs such as 5-fluorouracil (5-FU) are mostly metabolic analogues of purines or pyrimidines, which lack specificity for tumor cells and therefore have significant side effects. It is unclear whether there are other drugs that can target nucleotide metabolism, except for nucleic acid analogues. Here, we found that a natural compound, dehydroabietylamine (DHAA), significantly reduced the viability and proliferation of GC cells and organoids. DHAA disrupts purine and pyrimidine metabolism of GC cells, causing DNA damage and further inducing apoptosis. DHAA treatment decreased transcription and protein levels of key enzymes involved in nucleotide metabolism pathway, with significant reductions in the expression of pyrimidine metabolism key enzymes CAD, DHODH, and purine metabolism key enzymes PAICS. We also found that DHAA directly binds to and reduces the expression of Forkhead box K2 (FOXK2), a common transcription factor for these metabolic enzymes. Ultimately, DHAA was shown to delay tumorigenesis in K19-Wnt1/C2mE transgenic mice model and reduce levels of CAD, DHODH, and PAICS in vivo. We demonstrate that DHAA exerts an anticancer effect on GC by targeting transcription factor FOXK2, reducing transcription of key genes for nucleotide metabolism and impairing nucleotide biosynthesis, thus DHAA is a promising candidate for GC therapy.

Staphylococcal enterotoxin B exposed to pregnant rats inhibits the hedgehog signaling pathway in thymic T lymphocytes of the offspring.

The Hedgehog (Hh) signaling pathway is involved in T cell differentiation and development and plays a major regulatory part in different stages of T cell development. A previous study by us suggested that prenatal exposure to staphylococcal enterotoxin B (SEB) changed the percentages of T cell subpopulation in the offspring thymus. However, it is unclear whether prenatal SEB exposure impacts the Hh signaling pathway in thymic T cells. In the present study, pregnant rats at gestational day 16 were intravenously injected once with 15 µg SEB, and the thymi of both neonatal and adult offspring rats were aseptically acquired to scrutinize the effects of SEB on the Hh signaling pathway. It firstly found that prenatal SEB exposure clearly caused the increased expression of Shh and Dhh ligands of the Hh signaling pathway in thymus tissue of both neonatal and adult offspring rats, but significantly decreased the expression levels of membrane receptors of Ptch1 and Smo, transcription factor Gli1, as well as target genes of CyclinD1, C-myc, and N-myc in Hh signaling pathway of thymic T cells. These data suggest that prenatal SEB exposure inhibits the Hh signaling pathway in thymic T lymphocytes of the neonatal offspring, and this effect can be maintained in adult offspring via the imprinting effect.

OGNNMDA: a computational model for microbe-drug association prediction based on ordered message-passing graph neural networks.

In recent years, many excellent computational models have emerged in microbe-drug association prediction, but their performance still has room for improvement. This paper proposed the OGNNMDA framework, which applied an ordered message-passing mechanism to distinguish the different neighbor information in each message propagation layer, and it achieved a better embedding ability through deeper network layers. Firstly, the method calculates four similarity matrices based on microbe functional similarity, drug chemical structure similarity, and their respective Gaussian interaction profile kernel similarity. After integrating these similarity matrices, it concatenates the integrated similarity matrix with the known association matrix to obtain the microbe-drug heterogeneous matrix. Secondly, it uses a multi-layer ordered message-passing graph neural network encoder to encode the heterogeneous network and the known association information adjacency matrix, thereby obtaining the final embedding features of the microbe-drugs. Finally, it inputs the embedding features into the bilinear decoder to get the final prediction results. The OGNNMDA method performed comparative experiments, ablation experiments, and case studies on the aBiofilm, MDAD and DrugVirus datasets using 5-fold cross-validation. The experimental results showed that OGNNMDA showed the strongest prediction performance on aBiofilm and MDAD and obtained sub-optimal results on DrugVirus. In addition, the case studies on well-known drugs and microbes also support the effectiveness of the OGNNMDA method. Source codes and data are available at: https://github.com/yyzg/OGNNMDA.

Enantioselective α-Boryl Carbene Transformations.

Carbenes, recognized as potent intermediates, enable unique chemical transformations, and organoborons are pivotal in diverse chemical applications. As a hybrid of carbene and the boryl group, α-boryl carbenes are promising intermediates for the construction of organoborons; unfortunately, such carbenes are hard to access and have low structural diversity with their asymmetric transformations largely uncharted. In this research, we utilized boryl cyclopropenes as precursors for the swift synthesis of α-boryl metal carbenes, a powerful category of intermediates for chiral organoboron synthesis. These α-boryl carbenes undergo a series of highly enantioselective transfer reactions, including B-H and Si-H insertion, cyclopropanation, and cyclopropanation/Cope rearrangement, catalyzed by a singular chiral copper complex. This approach opens paths to previously unattainable but easily transformable chiral organoborons, expanding both carbene and organoboron chemistry.

Relationship among subjective exercise experience, exercise behavior, and trait anxiety in adolescents.

OBJECTIVE: To investigate the influence of subjective exercise experience on adolescent trait anxiety and to reveal the mediating effect of exercise behavior. METHODS: Using the Subjective Exercise Experience Scale (SEES), Physical Exercise Rating Scale (PARS-3), and Trait Anxiety Inventory (T-AI), a questionnaire survey was conducted among 500 adolescents in Southwest China, and the SPSS21.0 and AMOS21.0 statistical analysis software was used to statistics and analysis on the questionnaires. RESULTS: 1) Among adolescents, the exercise behavior of boys was significantly higher than that of girls (p < 0.05), and the subjective exercise experience of students aged 9 to 12 was significantly higher than that of students aged 12 to 15 (p < 0.05). 2) The subjective exercise experience could directly and positively predict exercise behavior (ß = 0.45, p < 0.001) and negatively predict trait anxiety (ß = -0.26, p < 0.05), and exercise behavior could directly and negatively predict trait anxiety (ß = -0.32, p < 0.01). 3) The exercise behavior played a partial mediating effect between subjective exercise experience and trait anxiety (the mediation effect was -0.14). Among them, compared with low- and high-exercise amounts, the exercise behavior of moderate exercise amounts had the strongest mediating effect between subjective exercise experience and trait anxiety. CONCLUSION: The good subjective exercise experience not only has direct benefits for improving trait anxiety in adolescents but also helps to improve their exercise behavior, enrich daily physical exercise activities, and indirectly promote the reduction of trait anxiety.

Genomic Characteristics of Okamejei kenojei and the Implications to Its Evolutionary Biology Study.

Okamejei kenojei is an important economic species widely distributed in shallow coastal waters of the western North Pacific. In this study, the whole-genome survey analysis of O. kenojei was conducted to reveal its genomic characteristics. The genome size was estimated to be 2027.44 Mb, the repeat sequence content was 44.90%, and the heterozygous ratio was 1.04%. The mitochondrial genome excavated from the sequencing data was 16,974 bp, and it can form the closed circular molecule. The phylogenetic tree based on 13 protein-coding gene sequences supported the validity of Okamejei and assisted the conclusion that Raja porosa was the junior synonym of O. kenojei. Plenty of potential microsatellite loci were identified, and the distribution frequency was estimated to be approximately 236.3 SSRs per Mb. Among all motif types of microsatellites, the dinucleotide repeats were dominant (82.59%), followed by the trinucleotide repeats (8.05%), tetranucleotide repeats (5.80%), pentanucleotide repeats (2.83%), and hexanucleotide repeats (0.72%). The results of the present study could not only provide useful information for understanding the genome structure and functional characteristics of O. kenojei, but also lay the foundation for the subsequent mapping of the whole genome.

Theoretical Study for Adsorption-Diffusion on H-MOR and Pyridine Pre-adsorbed H-MOR of Dimethyl Ether Carbonylation.

For dimethyl ether (DME) carbonylation, pyridine pre-adsorbed hydrogen mordenite (H-MOR) is beneficial to prolonging the catalyst life. The adsorption and diffusion behaviors on periodic models H-AlMOR and H-AlMOR-Py were simulated. The simulation was based on Monte Carlo and molecular dynamics. The following conclusions were drawn from the simulation results. The adsorption stability of CO in 8-MR is increased, and the adsorption density of CO in 8-MR is more concentrated on H-AlMOR-Py. 8-MR is the main active site for DME carbonylation, so the introduction of pyridine would be beneficial for the main reaction. The adsorption distributions of methyl acetate (MA) (in 12-MR) and H2O on H-AlMOR-Py are significantly decreased. It means the product MA and the byproduct H2O are more easily desorbed on H-AlMOR-Py. For the mixed feed of DME carbonylation, the feed ratio (PCO/PDME) must reach 50:1 on H-AlMOR so that the reaction molar ratio can reach the theoretical value (NCO/NDME ≈ 1:1), while the feed ratio on H-AlMOR-Py is only up to 10:1. Thus, the feed ratio can be adjusted, and raw materials can reduce consumption. In conclusion, H-AlMOR-Py can improve the adsorption equilibrium of reactants CO and DME and increase the concentration of CO in 8-MR.

Machine Learning in Unmanned Systems for Chemical Synthesis.

Chemical synthesis is state-of-the-art, and, therefore, it is generally based on chemical intuition or experience of researchers. The upgraded paradigm that incorporates automation technology and machine learning (ML) algorithms has recently been merged into almost every subdiscipline of chemical science, from material discovery to catalyst/reaction design to synthetic route planning, which often takes the form of unmanned systems. The ML algorithms and their application scenarios in unmanned systems for chemical synthesis were presented. The prospects for strengthening the connection between reaction pathway exploration and the existing automatic reaction platform and solutions for improving autonomation through information extraction, robots, computer vision, and intelligent scheduling were proposed.

Highly Regioselective Cobalt-Catalyzed Hydroboration of Internal Alkynes.

Herein, we report the development of new Co complexes that have cyclopropane-based diphosphine ligands and can catalyze highly chemo-, regio-, and stereoselective hydroboration reactions of unsymmetrical internal alkynes. These reactions exhibited unusual regioselectivity: specifically, reactions of aryl alkyl internal alkynes showed excellent cis-ß-addition selectivity, and reactions of dialkyl internal alkynes gave excellent cis-α-addition selectivity. Highly regioselective hydroboration of unsymmetrical dialkyl internal alkynes cannot be achieved by other known methods. The reactions described herein are highly synthetically useful, particularly for the stereoselective synthesis of trisubstituted alkenylborates and alkenes. Mechanistic studies indicate that a CoI -H species is a plausible active catalyst and the rigid structure of the cyclopropane skeleton of the ligands and the crowded reaction pocket were responsible for the unprecedented regioselectivity.

Prenatal Exposure of Rats to Staphylococcal Enterotoxin B Alters the Expression of Th1 and Th2 Cytokines via Decreased Methylation in the Spleen of Adult but not Neonatal Offspring.

BACKGROUND: The methylation of IFN-γ and IL-4 genes is regarded as an epigenetic regulation that maintains the Th1 or Th2 phenotype. OBJECTIVE: To explore the influence of prenatal administration of the staphylococcal enterotoxin B (SEB) in pregnant rats, on the IFN-γ or IL-4 expression in the offspring spleen. METHODS: The SEB or PBS was administered intravenously to pregnant rats on the embryo-day 16. After normal delivery, the spleens from the fifth-day neonates and adult offspring were isolated under anesthesia. Quantitative PCR, western blot, ELISA and MeDIP-qPCR were applied to determine the levels of the splenic IFN-γ or IL-4 mRNAs, their protein levels, and methylation status, respectively. RESULTS: Prenatal administration of the SEB in pregnant rats decreased the levels of the splenic IFN-γ and IL-4 proteins in neonates, but increased their mRNA levels. However, prenatal administration of the SEB significantly augmented both mRNA and protein levels of the IFN-γ and IL-4 in the adult spleen. In addition, the prenatal SEB administration decreased the methylation of the splenic IFN-γ and IL-4 in adult but not neonatal offspring. CONCLUSION: The prenatal administration of SEB in pregnant rats can cause a mixed Th1 and Th2 cytokines response in the offspring spleen, and alter the cytokine expression of the Th1 and Th2 via decreasing the methylation in adult but, not neonatal offspring spleen.

Period 2 Suppresses the Malignant Cellular Behaviors of Colorectal Cancer Through the Epithelial-Mesenchymal Transformation Process.

INTRODUCTION: The PER2 (Period circadian regulator 2) gene is related to the circadian clock, and it has been deemed as a suppressor gene in osteosarcoma and lung carcinoma. However, the part of PER2 in CRC (colorectal cancer) needs to be further determined. METHODS: First, we collected clinical samples to detect PER2 expression in CRC. Then, we used cell transfection to knock down PER2 expression in CRC cell lines and performed a series of functional experiments to elucidate the effects of PER2 on CRC cells. We next verified whether PER2 affects the epithelial-mesenchymal transformation (EMT) process in CRC by conducting quantitative real-time PCR and western blotting. RESULTS: In the research, we revealed that the expression of PER2 decreased in CRC clinical samples. In addition, knocking down PER2 expression caused CRC cells to acquire malignant biological features. Finally, we found that PER2 knockdown may activate the Snail/Slug axis through inhibiting p53, therefore promote the activation of the EMT pathway. CONCLUSION: In conclusion, low PER2 expression reinforces migration and activates EMT in CRC, suggesting that PER2 is closely related to CRC development and could be used as a potential treatment site in the clinic.

Identification of crucial genes of pyrimidine metabolism as biomarkers for gastric cancer prognosis.

BACKGROUND: Metabolic reprogramming has been reported in various kinds of cancers and is related to clinical prognosis, but the prognostic role of pyrimidine metabolism in gastric cancer (GC) remains unclear. METHODS: Here, we employed DEG analysis to detect the differentially expressed genes (DEGs) in pyrimidine metabolic signaling pathway and used univariate Cox analysis, Lasso-penalizes Cox regression analysis, Kaplan-Meier survival analysis, univariate and multivariate Cox regression analysis to explore their prognostic roles in GC. The DEGs were experimentally validated in GC cells and clinical samples by quantitative real-time PCR. RESULTS: Through DEG analysis, we found NT5E, DPYS and UPP1 these three genes are highly expressed in GC. This conclusion has also been verified in GC cells and clinical samples. A prognostic risk model was established according to these three DEGs by Univariate Cox analysis and Lasso-penalizes Cox regression analysis. Kaplan-Meier survival analysis suggested that patient cohorts with high risk score undertook a lower overall survival rate than those with low risk score. Stratified survival analysis, Univariate and multivariate Cox regression analysis of this model confirmed that it is a reliable and independent clinical factor. Therefore, we made nomograms to visually depict the survival rate of GC patients according to some important clinical factors including our risk model. CONCLUSION: In a word, our research found that pyrimidine metabolism is dysregulated in GC and established a prognostic model of GC based on genes differentially expressed in pyrimidine metabolism.

Inhibition of protein PMP22 enhances etoposide-induced cell apoptosis by p53 signaling pathway in Gastric Cancer.

Gastric Cancer (GC) is one of the main causes leading to death. PMP22, as a member of the GAS3 family of tetraspan proteins, it is associated with a variety of neurological diseases. Recently, more and more studies have shown that PMP22 play a great role in the physiological processes such as cells adhesion, migration, proliferation and tumorigenesis, but the involvement and functional mechanisms of PMP22 in Gastric carcinoma are not investigated clearly. In this study, we found that the PMP22 was overexpressed in the GC cells and tissue. Knockdown of PMP22 inhibits cell growth. Over-expressed PMP22 inhibits the etoposide-induced apoptosis, meanwhile knockdown of PMP22 promotes the etoposide-induced proliferation suppression, and increases cell apoptosis in GC cells. Furthermore, PMP22 enhanced the inhibition of the p53 transcriptional activities and down-regulated the p53 targeting genes, including p21, BAX and PUMA with or without treatment of etoposide. Finally, our results showed that PMP22 reduced the etoposide-induced tumor growth suppression in nude mice. Taken together, our research provided an anti-apoptotic properties alternative mechanism for PMP22 in gastric carcinoma and suggested PMP22 can be a potential target for the treatment of gastric cancer.

Candida albicans disorder is associated with gastric carcinogenesis.

Background: Bacterial infection is associated with gastric carcinogenesis. However, the relationship between nonbacterial components and gastric cancer (GC) has not been fully explored. We aimed to characterize the fungal microbiome in GC. Methods: We performed ITS rDNA gene analysis in cancer lesions and adjacent noncancerous tissues of 45 GC cases from Shenyang, China. Obtaining the OTUs and combining effective grouping, we carried out species identifications, alpha and beta diversity analyses, and FUNGuild functional annotation. Moreover, differences were compared and tested between groups to better investigate the composition and ecology of fungi associated with GC and find fungal indicators. Results: We observed significant gastric fungal imbalance in GC. Principal component analysis revealed separate clusters for the GC and control groups, and Venn diagram analysis indicated that the GC group showed a lower OTU abundance than the control. At the genus level, the abundances of 15 fungal biomarkers distinguished the GC group from the control, of which Candida (p = 0.000246) and Alternaria (p = 0.00341) were enriched in GC, while Saitozyma (p = 0.002324) and Thermomyces (p = 0.009158) were decreased. Combining the results of Welch's t test and Wilcoxon rank sum test, Candida albicans (C. albicans) was significantly elevated in GC. The species richness Krona pie chart further revealed that C. albicans occupied 22% and classified GC from the control with an area under the receiver operating curve (AUC) of 0.743. Random forest analysis also confirmed that C. albicans could serve as a biomarker with a certain degree of accuracy. Moreover, compared with that of the control, the alpha diversity index was significantly reduced in the GC group. The Jaccard distance index and the Bray abundance index of the PCoA clarified separate clusters between the GC and control groups at the species level (p = 0.00051). Adonis (PERMANOVA) analysis and ANOVA showed that there were significant differences in fungal structure among groups (p = 0.001). Finally, FUNGuild functional classification predicted that saprotrophs were the most abundant taxa in the GC group. Conclusions: This study revealed GC-associated mycobiome imbalance characterized by an altered fungal composition and ecology and demonstrated that C. albicans can be a fungal biomarker for GC. With the significant increase of C. albicans in GC, the abundance of Fusicolla acetilerea, Arcopilus aureus, Fusicolla aquaeductuum were increased, while Candida glabrata, Aspergillus montevidensis, Saitozyma podzolica and Penicillium arenicola were obviously decreased. In addition, C. albicans may mediate GC by reducing the diversity and richness of fungi in the stomach, contributing to the pathogenesis of GC.

Exposure of pregnant rats to staphylococcal enterotoxin B increases offspring splenic Treg number and function via decreasing FoxP3 methylation.

Staphylococcus aureus is an infectious pathogen that is relatively common, but that can cause severe disease in pregnant women and their fetus. We previously demonstrated that exposing pregnant rats to staphylococcal enterotoxin B (SEB) altered splenic CD4/CD8 T cell frequencies in their offspring. Whether prenatal SEB exposure impacts Tregs in these offspring, however, remains to be determined. As such, in this study, we intravenously injected pregnant rats with 15 µg of SEB on gestational day 16. Splenic tissue was then harvested from 1-, 3-, and 5-day-old neonatal rats and analyzed via flow cytometry to assess Treg numbers. In addition, FoxP3 expression levels were assessed via qPCR and western blotting, while FoxP3 methylation status was evaluated via methyl-DNA immunoprecipitation qPCR. Immunosuppression assays were additionally used to gauge Treg suppressive functionality. We found that exposing pregnant rats to SEB resulted in a significant increase in Treg numbers, FoxP3 expression, and Treg suppressive capacity in the spleens of both neonatal and adult offspring. In addition, total T cell, CD4+T cell, and non-Treg CD4+ T cell numbers were elevated in the spleens of offspring following prenatal SEB exposure. We additionally determined that SEB exposure resulted in a significant reduction in FoxP3 DNA methylation. Together, our results indicate that prenatal SEB exposure can markedly enhance offspring splenic Treg numbers and functionality at least in part by decreasing FoxP3 methylation.

Online and Unsupervised Anomaly Detection for Streaming Data Using an Array of Sliding Windows and PDDs.

In this article, we propose an online and unsupervised anomaly detection algorithm for streaming data using an array of sliding windows and the probability density-based descriptors (PDDs) (based on these windows). This algorithm mainly consists of three steps: 1) we use a main sliding window over streaming data and segment this window into an array of nonoverlapping subwindows; 2) we propose the PDDs with dimension reduction, based on the kernel density estimation, to estimate the probability density of data in each subwindow; and 3) we design the distance-based anomaly detection rule to determine whether the current observation is anomalous. The experimental results and performances are presented based on the Numenta anomaly benchmark. Compared with the anomaly detection algorithm using the hierarchical temporal memory proposed by Numenta (which outperforms a wide range of other anomaly detection algorithms), our algorithm can perform better in many cases, that is, with higher detection rates and earlier detection for contextual anomalies and concept drifts.

Microbial Community Profiling Distinguishes Left-Sided and Right-Sided Colon Cancer.

The difference between left- and right-sided colon cancer has become the focus of global attention, and researchers have found differences in the morbidity, molecular biological characteristics, and response to targeted drug therapy between left- and right-sided colon cancer. Therefore, the identification of more effective predictive indicators is critical for providing guidance to future clinical work. We collected samples from different colon sites and regions and analyzed the identities and distributions of differentially expressed species in the microbiota in the left and right sides of the colon to better explore the pathogenesis of colon cancer and provided a basis for individualized drug therapy. We collected samples from different regions in the body of 40 patients with colon cancer, including stool and tissues. The Subjects were classified into four groups, and this classification was mainly based on the colon cancer distribution. The microbiota composition of the left-sided and right-sided colon samples was assessed by specifically amplifying the V3-V4 region of the 16S rDNA gene from DNA extracts from the samples. These amplicons were examined by Illumina HiSeq 2500 sequencing. The microbial taxa in the left-sided colon samples are more abundant than those in the right-sided colon samples. The flora in the left-sided colon samples, such as Clostridium perfringens and Fusobacterium nucleatum, might be associated with VEGF expression and are more likely to promote colon cancer. The microbiota distribution in the right-sided colon samples is less invasive and harmful and particularly rich in Bifidobacterium dentium. In addition, Streptococcus, which is the target of EGFR, was found to be expressed in both the left- and right-sided colon samples but was found at a higher level in the left-sided colon samples. Additionally, the differential pathways involved in the left-sided colon samples mainly mediate DNA damage, methylation, and histone modifications, whereas those in the right-sided colon samples are dominated by DNA synthesis. The comparison of only the geographical differences revealed a significant difference in the distribution of the microbial population. The adherent microbiota composition and structural changes between the left- and right-sided colon samples might contribute to the development of colon cancer, lead to different morbidities, and further affect the prognosis of patients and their sensitivity to targeted drugs. Therefore, the identification of the differential flora in the colon could be used as an indicator for predicting the occurrence and development of colon cancer, which is also beneficial for future individualized drug therapy.

Identification of the Combinatorial Effect of miRNA Family Regulatory Network in Different Growth Patterns of GC.

According to the growth pattern, gastric cancer (GC) could be classified into expanding-type GC and infiltrative-type GC (Ming's classification). The growth pattern of GC is often related to the malignant degree, invasion, metastasis, and other pathological characteristics of tumors. MicroRNAs (miRNAs) play important roles in modulating gene expression during the GC development. In this study, miR-29s were significantly correlated with the gastric carcinogenesis and Ming's classification. Biological function of miR-29s is most closely related to the pathway of extracellular matrix (ECM)-receptor interaction. ECM structural assembly, cell movement, and cell adhesion are the main functional categories of target genes in this pathway. Among these targets, the COL4A1 gene ranked at the top in the association analysis of combined miR-29s biological function and GC subtype, and miR-29s inhibited its translation by binding to the 3' UTR region. Infiltrative-type GC cells secrete a higher level of COL4A1 protein than do expanding-type GC cells. The expression of COL4A1 in GC is correlated with clinicopathological features. Downregulation of COL4A1 expression significantly inhibited the migration and invasion of GC cells. High COL4A1 expression was correlated with poor prognosis in survival analysis. The miR-29s regulatory network may affect the development of growth patterns and pathological progress of GC by regulating the function of COL4A1.

PLK1/NF-κB feedforward circuit antagonizes the mono-ADP-ribosyltransferase activity of PARP10 and facilitates HCC progression.

Dysregulation of PARP10 has been implicated in various tumor types and plays a vital role in delaying hepatocellular carcinoma (HCC) progression. However, the mechanisms controlling the expression and activity of PARP10 in HCC remain mostly unknown. The crosstalk between PLK1, PARP10, and NF-κB pathway in HCC was determined by performing different in vitro and in vivo assays, including mass spectrometry, kinase, MARylation, chromatin immunoprecipitation, and luciferase reporter measurements. Functional examination was performed by using small chemical drug, cell culture, and mice HCC models. Correlation between PLK1, NF-κB, and PARP10 expression was determined by analyzing clinical samples of HCC patients with using immunohistochemistry. PLK1, an important regulator for cell mitosis, directly interacts with and phosphorylates PARP10 at T601. PARP10 phosphorylation at T601 significantly decreases its binding to NEMO and disrupts its inhibition to NEMO ubiquitination, thereby enhancing the transcription activity of NF-κB toward multiple target genes and promoting HCC development. In turn, NF-κB transcriptionally inhibits the PARP10 promoter activity and leads to its downregulation in HCC. Interestingly, PLK1 is mono-ADP-ribosylated by PARP10 and the MARylation of PLK1 significantly inhibits its kinase activity and oncogenic function in HCC. Clinically, the expression levels of PLK1 and phosphor-p65 show an inverse correlation with PARP10 expression in human HCC tissues. These findings are the first to uncover a PLK1/PARP10/NF-κB signaling circuit that underlies tumorigenesis and validate PLK1 inhibitors, alone or with NF-κB antagonists, as potential effective therapeutics for PARP10-expressing HCC.