Defensive behavior is linked to altered surface chemistry following infection in a termite society.

The care-kill response determines whether a sick individual will be treated or eliminated from an insect society, but little is known about the physiological underpinnings of this process. We exploited the stepwise infection dynamics of an entomopathogenic fungus in a termite to explore how care-kill transitions occur, and identify the chemical cues behind these shifts. We found collective responses towards pathogen-injected individuals to vary according to severity and timing of pathogen challenge, with elimination, via cannibalism, occurring sooner in response to a severe active infection. However, injection with inactivated fungal blastospores also resulted in increased albeit delayed cannibalism, even though it did not universally cause host death. This indicates that the decision to eliminate an individual is triggered before pathogen viability or terminal disease status has been established. We then compared the surface chemistry of differently challenged individuals, finding increased amounts of long-chained methyl-branched alkanes with similar branching patterns in individuals injected with both dead and viable fungal blastospores, with the latter showing the largest increase. This coincided with the highest amounts of observed cannibalism as well as signs of severe moribundity. Our study provides new mechanistic insight into the emergent collective behaviors involved in the disease defense of a termite society.

Comparative analysis of adipokinetic hormones and their receptors in Blattodea reveals novel patterns of gene evolution.

Adipokinetic hormone (AKH) is a neuropeptide produced in the insect corpora cardiaca that plays an essential role in mobilising carbohydrates and lipids from the fat body to the haemolymph. AKH acts by binding to a rhodopsin-like G protein-coupled receptor (GPCR), the adipokinetic hormone receptor (AKHR). In this study, we tackle AKH ligand and receptor gene evolution as well as the evolutionary origins of AKH gene paralogues from the order Blattodea (termites and cockroaches). Phylogenetic analyses of AKH precursor sequences point to an ancient AKH gene duplication event in the common ancestor of Blaberoidea, yielding a new group of putative decapeptides. In total, 16 different AKH peptides from 90 species were obtained. Two octapeptides and seven putatively novel decapeptides are predicted for the first time. AKH receptor sequences from 18 species, spanning solitary cockroaches and subsocial wood roaches as well as lower and higher termites, were subsequently acquired using classical molecular methods and in silico approaches employing transcriptomic data. Aligned AKHR open reading frames revealed 7 highly conserved transmembrane regions, a typical arrangement for GPCRs. Phylogenetic analyses based on AKHR sequences support accepted relationships among termite, subsocial (Cryptocercus spp.) and solitary cockroach lineages to a large extent, while putative post-translational modification sites do not greatly differ between solitary and subsocial roaches and social termites. Our study provides important information not only for AKH and AKHR functional research but also for further analyses interested in their development as potential candidates for biorational pest control agents against invasive termites and cockroaches.

Unraveling the dynamic impacts of COVID-19 on metro ridership: An empirical analysis of Beijing and Shanghai, China.

The outbreak of coronavirus disease 2019 (COVID-19) has had severely disruptive impacts on transportation, particularly public transit. To understand metro ridership changes due to the COVID-19 pandemic, this study conducts an in-depth analysis of two Chinese megacities from January 1, 2020, to August 31, 2021. Generalized linear models are used to explore the impact of the COVID-19 pandemic on metro ridership. The dependent variable is the relative change in metro ridership, and the independent variables include COVID-19, socio-economic, and weather variables. The results suggested the following: (1) The COVID-19 pandemic has a significantly negative effect on the relative change in metro ridership, and the number of cumulative confirmed COVID-19 cases within 14 days performs better in regression models, which reflects the existence of the time lag effect of the COVID-19 pandemic. (2) Emergency responses are negatively associated with metro system usage according to severity and duration. (3) The marginal effects of the COVID-19 variables and emergency responses are larger on weekdays than on weekends. (4) The number of imported confirmed COVID-19 cases only significantly affects metro ridership in the weekend and new-normal-phase models for Beijing. In addition, the daily gross domestic product and weather variables are significantly associated with metro ridership. These findings can aid in understanding the usage of metro systems in the outbreak and new-normal phases and provide transit operators with guidance to adjust services.

Eating in a losing cause: limited benefit of modified macronutrient consumption following infection in the oriental cockroach Blatta orientalis.

BACKGROUND: Host-pathogen interactions can lead to dramatic changes in host feeding behaviour. One aspect of this includes self-medication, where infected individuals consume substances such as toxins or alter their macronutrient consumption to enhance immune competence. Another widely adopted animal response to infection is illness-induced anorexia, which is thought to assist host immunity directly or by limiting the nutritional resources available to pathogens. Here, we recorded macronutrient preferences of the global pest cockroach, Blatta orientalis to investigate how shifts in host macronutrient dietary preference and quantity of carbohydrate (C) and protein (P) interact with immunity following bacterial infection. RESULTS: We find that B. orientalis avoids diets enriched for P under normal conditions, and that high P diets reduce cockroach survival in the long term. However, following bacterial challenge, cockroaches significantly reduced their overall nutrient intake, particularly of carbohydrates, and increased the relative ratio of protein (P:C) consumed. Surprisingly, these behavioural shifts had a limited effect on cockroach immunity and survival, with minor changes to immune protein abundance and antimicrobial activity between individuals placed on different diets, regardless of infection status. CONCLUSIONS: We show that cockroach feeding behaviour can be modulated by a pathogen, resulting in an illness-induced anorexia-like feeding response and a shift from a C-enriched to a more P:C equal diet. However, our results also indicate that such responses do not provide significant immune protection in B. orientalis, suggesting that the host's dietary shift might also result from random rather than directed behaviour. The lack of an apparent benefit of the shift in feeding behaviour highlights a possible reduced importance of diet in immune regulation in these invasive animals, although further investigations employing pathogens with alternative infection strategies are warranted.

ZRANB1 enhances stem-cell-like features and accelerates tumor progression by regulating Sox9-mediated USP22/Wnt/ß-catenin pathway in colorectal cancer.

The pathogenesis of colorectal cancer (CRC) is a multistep process characterized by the accumulation of gene mutations and epigenetic alterations. Tumor necrosis factor receptor-associated factor-binding protein domain (ZRANB1) is a deubiquitinase that mediates tumor growth and metastasis by deubiquitinating target proteins. In this study, we examined the regulatory effects of ZRANB1 on the maintenance of cancer stem cell (CSC) properties and tumor growth in CRC. Human CRC tissue samples and matched normal tissues were collected for the analysis of ZRANB1 expression. ZRANB1 was upregulated in CRC human tissues and cell lines, and its expression was positively correlated with advanced tumor stage and poor survival of CRC patients. The overexpression of ZRANB1 also induced the expression of CSC markers in CRC cells. Then, a xenograft model was established by inoculating BALB/c mice with CRC cells. The upregulation of ZRANB1 promoted tumorigenesis in vivo. Sox9 is a transcription factor that acts as an oncogene in human cancers. ZRANB1 increased the stability of Sox9 in CRC cells by decelerating its ubiquitination. Further analysis revealed that Sox9 regulated the transcription activity of USP22 by binding to its promoter. Moreover, ZRANB1 enhances stem-cell-like features of CRC cells and activated the Wnt/ß-catenin pathway through USP22. Our results highlighted the role of ZRANB1 as a molecular target for CRC treatment, which may contribute to the development of novel therapies with better efficacy.

Determining the effects of Ephrin Type B Receptor 6 and Type A Receptor 3 on facilitating colorectal epithelial cell malignant transformation.

Ephrin Type-A Receptor 3 (EphA3) and Ephrin Type-B Receptor 6 (EphB6) belong to the ephrin receptor group consisting of the largest subset of receptor tyrosine kinases (RTKs) and are essential for neurogenesis and embryogenesis. The current study aimed to evaluate their functional roles in transforming colorectal epithelial cells and dissect the underlying molecular mechanisms. We observed altered EphA3 and EphB6 expression in tumor tissues as compared to normal tissues in a tissue microarray study. Enforced EphB6 expression promoted IMCE cell proliferation, migration, and invasion in vitro and tumor formation in nude mice, with a stronger oncogenic activity than EphA3. Pathway analysis of differentially expressed genes from a gene microarray study provided important insight into potential mechanisms through which EphB6 may regulate the malignant transformation of colorectal epithelial cells. This study represents the first demonstration of EphB6 in enhancing colorectal epithelial cell transformation, suggesting its stipulative role in the early stage of colorectal tumorigenesis. Our findings primarily uncover novel biomarkers and therapeutic targets of colorectal cancer.

Microsatellite-based analysis of genetic structure and gene flow of Mythimna separata (Walker) (Lepidoptera: Noctuidae) in China.

The oriental armyworm, Mythimna separata, is a serious agricultural pest in China. Seasonal and roundtrip migration has recently led to sudden, localized outbreaks and crop losses. To evaluate genetic differentiation between populations in eastern and western China and elucidate gene flow, the genetic structure of 20 natural populations from nine provinces was examined using seven microsatellite markers. The results indicated high genetic diversity. However, little to moderate (0 < F ST < 0.15) genetic differentiation was detected, and there was no correlation between genetic distance and geographical distance. Bayesian clustering analysis identified three groups whereas discriminant analysis of principal components identified ten clusters that were considered as two clear-cut clusters and one admixed group. Gene flow occurred frequently in most population pairs, and an asymmetrical migration rate was detected in several pairwise population comparisons. The bottleneck test showed that few populations had experienced recent bottlenecks. Correspondingly, large-scale and long-distance migration of M. separata has caused low genetic differentiation and frequent gene exchange. Our findings are important for studying genetic evolution and help to improve predictions of M. separata outbreaks in China.

MiR-30-5p suppresses cell chemoresistance and stemness in colorectal cancer through USP22/Wnt/ß-catenin signaling axis.

Colorectal cancer (CRC) remains both common and fatal, and its successful treatment is greatly limited by the development of stem cell-like characteristics (stemness) and chemoresistance. MiR-30-5p has been shown to function as a tumor suppressor by targeting the Wnt/ß-catenin signaling pathway, but its activity in CRC has never been assessed. We hypothesized that miR-30-5p exerts anti-oncogenic effects in CRC by regulating the USP22/Wnt/ß-catenin signaling axis. In the present study, we demonstrate that tissues from CRC patients and human CRC cell lines show significantly decreased miR-30-5p family expression. After identifying the 3'UTR of USP22 as a potential binding site of miR-30-5p, we constructed a luciferase reporter containing the potential miR-30-5p binding site and measured the effects on USP22 expression. Western blot assays showed that miR-30-5p decreased USP22 protein expression in HEK293 and Caco2 CRC cells. To evaluate the effects of miR-30-5p on CRC cell stemness, we isolated CD133 + CRC cells (Caco2 and HCT15). We then determined that, while miR-30-5p is normally decreased in CD133 + CRC cells, miR-30-5p overexpression significantly reduces expression of stem cell markers CD133 and Sox2, sphere formation, and cell proliferation. Similarly, we found that miR-30-5p expression is normally reduced in 5-fluorouracil (5-FU) resistant CRC cells, whereas miR-30-5p overexpression in 5-FU resistant cells reduces sphere formation and cell viability. Inhibition of miR-30-5p reversed the process. Finally, we determined that miR-30-5p attenuates the expression of Wnt/ß-catenin signaling target genes (Axin2 and MYC), Wnt luciferase activity, and ß-catenin protein levels in CRC stem cells.

A bi-objective integer programming model for partly-restricted flight departure scheduling.

The normal studies on air traffic departure scheduling problem (DSP) mainly deal with an independent airport in which the departure traffic is not affected by surrounded airports, which, however, is not a consistent case. In reality, there still exist cases where several commercial airports are closely located and one of them possesses a higher priority. During the peak hours, the departure activities of the lower-priority airports are usually required to give way to those of higher-priority airport. These giving-way requirements can inflict a set of changes on the modeling of departure scheduling problem with respect to the lower-priority airports. To the best of our knowledge, studies on DSP under this condition are scarce. Accordingly, this paper develops a bi-objective integer programming model to address the flight departure scheduling of the partly-restricted (e.g., lower-priority) one among several adjacent airports. An adapted tabu search algorithm is designed to solve the current problem. It is demonstrated from the case study of Tianjin Binhai International Airport in China that the proposed method can obviously improve the operation efficiency, while still realizing superior equity and regularity among restricted flows.

Ubiquitin-Specific Peptidase 22 Contributes to Colorectal Cancer Stemness and Chemoresistance via Wnt/ß-Catenin Pathway.

BACKGROUND/AIMS: Two major barriers to the successful treatment of colorectal cancer (CRC) are the development of stem cell-like characteristics (stemness) and chemoresistance. Ubiquitin-specific peptidase 22 (USP22) is a deubiquitinating enzyme and putative CRC marker that has emerged as a potential cause of both phenomena in CRC. There is evidence that USP22 acts through the Wnt/ß-catenin pathway and that downregulation of the latter may reduce chemoresistance. METHODS: In this study, we used CRC tissue specimens from human patients as well as human CRC cell lines to evaluate the role of USP22 in CRC stemness and chemoresistance in vitro and in vivo. RT-PCR and western blot were used for gene expression analyses. Immunohistochemistry was performed for USP22 expression in clinical samples. CD133 levels were analyzed by flow cytometry. Sphere formation and MTT assays were used for self-renewal and proliferation analysis. Chemoresistance was evaluated by cell viability and sphere formation assays. RESULTS: We found a significant increase of USP22 in recurrent CRC and chemoresistant CRC cells as compared to primary CRC and non-chemoresistant CRC cells, respectively. We then demonstrated that USP22 mediates CRC cell chemoresistance through the Wnt/ß-catenin pathway and that reducing USP22 in CRC cells diminishes chemoresistance. CONCLUSIONS: Having established the crucial role of USP22 in CRC stemness and chemoresistance, this study suggests that USP22 may be an ideal genetic target in the treatment of chemoresistant CRC.

Driving behavior recognition using EEG data from a simulated car-following experiment.

Driving behavior recognition is the foundation of driver assistance systems, with potential applications in automated driving systems. Most prevailing studies have used subjective questionnaire data and objective driving data to classify driving behaviors, while few studies have used physiological signals such as electroencephalography (EEG) to gather data. To bridge this gap, this paper proposes a two-layer learning method for driving behavior recognition using EEG data. A simulated car-following driving experiment was designed and conducted to simultaneously collect data on the driving behaviors and EEG data of drivers. The proposed learning method consists of two layers. In Layer I, two-dimensional driving behavior features representing driving style and stability were selected and extracted from raw driving behavior data using K-means and support vector machine recursive feature elimination. Five groups of driving behaviors were classified based on these two-dimensional driving behavior features. In Layer II, the classification results from Layer I were utilized as inputs to generate a k-Nearest-Neighbor classifier identifying driving behavior groups using EEG data. Using independent component analysis, a fast Fourier transformation, and linear discriminant analysis sequentially, the raw EEG signals were processed to extract two core EEG features. Classifier performance was enhanced using the adaptive synthetic sampling approach. A leave-one-subject-out cross validation was conducted. The results showed that the average classification accuracy for all tested traffic states was 69.5% and the highest accuracy reached 83.5%, suggesting a significant correlation between EEG patterns and car-following behavior.

EphA3 promotes malignant transformation of colorectal epithelial cells by upregulating oncogenic pathways.

Ephrin Type-A Receptor 3 (EphA3) belongs to the ephrin receptor subfamily of the protein tyrosine kinase family, and plays an important role in embryogenesis and neurogenesis. This study aimed to investigate the role of EphA3 in promoting malignant transformation of colorectal epithelial cells, and explore underlying molecular mechanisms. Colorectal cancer tissue specimens from 68 patients were analyzed for EphA3 expression. EphA3 expression levels were manipulated in rat colon epithelial cell lines. We found that EphA3 expression level in tumor tissues was associated with patient age (P = 0.015), tumor differentiation (P = 0.001), and lymph node metastasis (P = 0.039). Overexpression of EphA3 and its constitutively active mutants promoted colony formation, migration and invasion, and tumorigenicity of colon epithelial cells in nude mice. The cDNA and lncRNA microarray profiling data revealed that differentially expressed genes and lncRNAs in EphA3 or mutant-transfected cells were associated with cell proliferation, invasion and angiogenesis. Our findings reveal the mechanisms underlying the oncogenic activities of EphA3 in colorectal cells, which could provide novel targets for the prevention, early diagnosis, and treatment of colorectal cancer.

Efficient line-based lens distortion correction for complete distortion with vanishing point constraint.

The line-based correction method has been widely researched to improve the performance of lens distortion correction. However, due to the coupling of the distortion parameters and the inaccuracy of line equation estimation, it is difficult to achieve high-accuracy correction under the complete lens distortion (composed of radial, decentering, and prism distortion). Here, we present a method that utilizes two models to resolve these two problems, respectively: the recursive individual optimization model decouples the distortion parameters by applying Levenberg-Marquardt to optimize the parameters individually, and the vanishing point reprojection model improves the accuracy of line equation estimation with the known vanishing points calculated by a proposed expectation-minimization algorithm. Therefore, accurate correction of complete distortion can be achieved by the line information only. The validity of the proposed method was tested by several synthetic and real data, and the results showed that this method can correct the image with the complete and noncomplete distortion effectively.

MicroRNA-375 inhibits colorectal cancer growth by targeting PIK3CA.

Colorectal cancer (CRC) is the second most common cause of death from cancer. MicroRNAs (miRNAs) represent a class of small non-coding RNAs that control gene expression by triggering RNA degradation or interfering with translation. Aberrant miRNA expression is involved in human disease including cancer. Herein, we showed that miR-375 was frequently down-regulated in human colorectal cancer cell lines and tissues when compared to normal human colon tissues. PIK3CA was identified as a potential miR-375 target by bioinformatics. Overexpression of miR-375 in SW480 and HCT15 cells reduced PIK3CA protein expression. Subsequently, using reporter constructs, we showed that the PIK3CA untranslated region (3'-UTR) carries the directly binding site of miR-375. Additionally, miR-375 suppressed CRC cell proliferation and colony formation and led to cell cycle arrest. Furthermore, miR-375 overexpression resulted in inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. SiRNA-mediated silencing of PIK3CA blocked the inhibitory effect of miR-375 on CRC cell growth. Lastly, we found overexpressed miR-375 effectively repressed tumor growth in xenograft animal experiments. Taken together, we propose that overexpression of miR-375 may provide a selective growth inhibition for CRC cells by targeting PI3K/Akt signaling pathway.

Prognostic significance of lymph node status in patients with metastatic colorectal carcinoma treated with lymphadenectomy.

BACKGROUND AND OBJECTIVES: To test prognostic significance of lymph node status in patients with metastatic colorectal carcinoma (mCRC). METHODS: Four hundred ninety six patients diagnosed with synchronous mCRC and treated with lymphadenectomy between 1995 and 2008 were identified and divided into groups pN0, pN1, and pN2 (140 (28.2%) in pN0, 223 (45.0%) in pN1, and 133 (26.8%) in pN2 group) according to their lymph node status. The Kaplan-Meier and Cox regression analyses were used to test associations and independent predictor status of lymph node involvement. RESULTS: The Cox proportional hazards regression showed pN as significantly associated with disease-specific survival (DSS) both in univariate (HR = 1.609, 95% CI 1.411 to 1.835, P < 0.001) and multivariate (HR = 1.630, 95% CI 1.422 to 1.868, P < 0.001) analyses. The Kaplan-Meier analysis demonstrated that patients with pN2 and pN1 had a significantly worse DSS compared with patients with pN0 tumors (respectively, 17.273 ± 1.020 and 27.145 ± 1.715 vs. 34.992 ± 2.143 months; P < 0.001). In accuracy analyses based on AUC values, nodal status demonstrated the highest accuracy (65.1%) out of all the variables. CONCLUSIONS: Our findings indicate that optimal TNM staging for mCRC should incorporate lymph node status to provide a more effective and predictive model.

Anti-colorectal cancer activity of macrostemonoside A mediated by reactive oxygen species.

Macrostemonoside A (MSS.A), an active steroidal saponin from Allium macrostemon Bung has been shown to possess anti-coagulation and anti-obesity effects. However, the functional role of MSS.A on tumor growth has not been elucidated. We found that MSS.A significantly inhibited human colorectal cancer cell growth in Caco2 and SW480 cells. Incubation of SW480 cells with MSS.A for 48 h resulted in cell cycle arrest. Moreover, MSS.A dose-dependently induced apoptosis in SW480 cells as shown by increased AnnexinV positively stained cell population, caspase activation, increased pro-apoptotic and reduced anti-apoptotic Bcl-2 family protein levels. Treatment of SW480 cells with MSS.A resulted in increased reactive oxygen species (ROS) generation. However, pre-incubation of SW480 cells with antioxidant N-acetylcysteine (NAC) attenuated the ROS generation and anti-colorectal cancer activities of MSS.A. Lastly, intra-peritoneal injections of MSS.A significantly inhibited tumor formation in BALB/c nude mice carcinogenesis xenograft model by reduced tumor volume and tumor weight when treated at dosages of 10, 50 or 100mg/kg daily for 35 days compared with PBS control. Taken together, our results indicate that MSS.A suppressed colorectal cancer growth and induced cell apoptosis by inducing ROS production, and that MSS.A may have therapeutic relevance in the treatment of human colorectal cancer.

The influence of genetic polymorphisms in MDR1 gene on breast cancer risk factors in Chinese.

Breast cancer (BC) is the most common cancer among women in the world. The human multidrug resistance 1 gene (MDR1) is potentially an important gene influencing the susceptibility to breast cancer. This study aimed to assess the association of MDR1 genetic polymorphisms with the susceptibility to BC. Overall, 353 BC patients and 360 cancer-free controls were enrolled. The clinical characteristics were summarized by questionnaires. The c.1564A > T genetic polymorphism was genotyped using created restriction site-polymerase chain reaction method. We found that no significant differences in the genotypic and allelic frequencies between BC patients and cancer-free controls. Furthermore, the distribution of BC patients' risk factors was not significantly different among AA, AT, and TT genotypes. Our findings indicate that the c.1564A > T genetic polymorphism is not significantly associated with the susceptibility to BC in Chinese Han populations.

ING4 is negatively correlated with microvessel density in colon cancer.

ING4 is a novel tumor suppressor which is downregulated in a number of cancers. In this study, we investigated the role of ING4 in tumor angiogenesis in colorectal carcinoma (CRC) patients. Semi-quantitative RT-PCR, western blots, and immunohistochemistry were used to determine ING4 mRNA and protein expression in CRC and normal tissue from 60 CRC specimens and 30 colonic adenoma specimens. The correlation between ING4 expression and clinical stage, histological grade as well as lymph node metastasis was evaluated. Immunohistochemistry was performed to explore the correlation between ING4 expression and microvessel density (MVD) in CRC. CRC tissue had significantly lower levels of ING4 mRNA and protein compared to colonic adenoma and normal intestinal tissue. Immunostaining showed ING4 expression in 38 (63.3 %), 30 (100 %), and 60 (100 %) cases of normal colonic mucosa, adenoma, and normal intestinal mucosal tissue, respectively. Lower ING4 levels correlated with higher clinical stage and histological grade. ING4 mRNA and protein levels were significantly lower in CRC patients with lymph node metastasis compared to patients without lymph node metastasis (0.41 ± 0.30 vs. 0.91 ± 0.29 and 0.60 ± 0.21 vs. 0.87 ± 0.27, respectively; p < 0.001). Importantly, ING4 mRNA and protein levels were negatively correlated with MVD in CRC patients (p < 0.001). Our data suggest that ING4 levels are a potential biomarker of CRC progression and that ING4 may inhibit tumor growth by modulating angiogenesis in CRC.

USP22 acts as an oncogene by the activation of BMI-1-mediated INK4a/ARF pathway and Akt pathway.

Recent studies provided strong support for the view that ubiquitin-specific protease 22 (USP22) plays a central role in cell-cycle progression and also in pathological processes such as oncogenesis. We have recently shown that USP22 levels are elevated in colorectal carcinoma with associated increase in the expression of several cell-cycle-related genes. However, the precise mechanism for these functions of USP22 at molecular level has not been fully elucidated. Currently, we investigated the role of USP22 in human colorectal cancer (CRC). We observed that USP22 expression was statistically significantly correlated positively with that of BMI-1, c-Myc and both, pAkt (Ser473), and pAkt (Thr308), in primary tumor tissues from 43 CRC patients. Down-regulation of USP22 expression in HCT116 colorectal cancer cells by siRNA resulted in the accumulation of cells in the G1 phase of the cell cycle. RNAi-knockdown of USP22 in HCT16 cells also led to the repression of BMI-1 and was accompanied by the up-regulation of p16INK4a and p14ARF, with a consequent decrease in E2F1 and p53 levels. In addition, down-regulation of c-Myc-targeted cyclin D2 was also noticed in cells treated with USP22-siRNA. Furthermore, our results showed that USP22 deletion also caused down-regulation of Akt/GSK3ß activity, which can also contribute to the reduction of cyclin D2. Collectively, our current results suggest that USP22 may act as an oncogene in CRC as it positively regulates cell cycle via both BMI-1-mediated INK4a/ARF pathway and Akt signaling pathway.

The role of para-aortic lymphadenectomy in surgical management of patients with stage N+ rectal cancer below the peritoneal reflection.

The goal of this retrospective study was to determine the effect of para-aortic lymphadenectomy on clinical outcome in patients with stage N+ rectal adenocarcinoma below the peritoneal reflection. A retrospective analysis was performed on the clinical outcome of 181 patients with stage N+ rectal adenocarcinoma below the peritoneal reflection who underwent total mesorectal excision (TME) with total pelvic lymph node (PLN) adenectomy, with or without para-aortic lymph node (PAN) adenectomy. Independent prognostic factors were determined by multivariate Cox regression analysis. Disease-free survival (DFS) was analyzed using Kaplan-Meier curves and the log-rank test. The incidence of PLN metastases was 39.2% (71/181) in all the patients, and the incidence of PAN metastases was 12% (12/100) in patients who received PLN + PAN adenectomies. The patients were divided into two groups: PLN adenectomy (n = 81) and PLN + PAN adenectomy (n = 100). There were no statistically significant differences in clinicopathological factors between the PLN adenectomy and PLN + PAN adenectomy groups. On univariate analysis, the gross tumor type (P = 0.012), histological differentiation (P = 0.013), CEA level (P = 0.019), T stage (P = 0.019), N stage (P < 0.0001), and the number of positive PLN sites (P < 0.0001) were associated with poor DFS. Gross tumor type (P = 0.031), N stage (P = 0.001), and the number of positive PLN sites (P < 0.0001) were independent prognostic factors for DFS as identified by multivariate Cox regression analysis. PLN + PAN adenectomy significantly improved DFS compared to PLN adenectomy alone in patients with noninfiltrating type (P = 0.001), but not in patients with infiltrating type (P = 0.075). PLN + PAN adenectomy significantly improved DFS compared to PLN adenectomy alone in patients with 0 or 1 positive PLN site (P = 0.001, P = 0.009 respectively), but not in patients with ≥2 positive PLN sites (P = 0.095). In the N1 and N2 stage groups, PLN + PAN adenectomy significantly improved DFS compared with PLN adenectomy alone (P = 0.001; P < 0.0001, respectively). Furthermore, mean DFS was longer in the absence of PAN metastasis (P < 0.0001). PAN metastases appear to be associated with reduced DFS. Total PAN adenectomy may improve DFS in patients with noninfiltrating type, stage III rectal cancer below the peritoneal reflection, who have <2 positive PLN sites.