Novel evidence for oncogenic piRNA-823 as a promising prognostic biomarker and a potential therapeutic target in colorectal cancer.

piRNA-823 as a member of the piRNA family is reported to promote tumour cell proliferation in multiple myeloma and hepatocellular cancer. However, few studies on the function of piRNA-823 in colorectal cancer (CRC). Our present study data showed that piRNA-823 plays an oncogene role in CRC cells. Inhibition of piRNA-823 can significantly inhibit the proliferation, invasion and apoptosis resistance of CRC cells. Mechanism studies have shown that piRNA-823 inhibits the ubiquitination of hypoxia-inducible factor-1 alpha (HIF-1α) by up-regulating the expression of Glucose-6-phosphate dehydrogenase (G6PD) and ultimately up-regulates the glucose consumption of carcinoma cells and inhibits the content of intracellular reactive oxygen species (ROS). Therefore, we speculate piRNA-823 promotes the proliferation, invasion and apoptosis resistance of CRC cells by regulating G6PD/HIF-1α pathway. In this study, we set up the cancer-promoting function recovery experiment of piRNA-823 by silencing G6PD gene to confirm the dominance of the above-mentioned pathways. Using clinical samples, we found that overexpression of piRNA-823 correlated with poor overall survival and predicted a poor response to adjuvant chemotherapy of patients with CRC. In a word, our research has further enriched the theory of piRNA-823 promoting the progression of CRC, and laid a solid foundation for the development of piRNA-823-based gene therapy for CRC and its use as a promising prognostic biomarker in CRC patients.

The development of methods for primary mast cells in vitro and ex vivo: An historical review.

Mast cells (MCs) are tissue-based stationary effector cells that form the immune system's first-line defense against various challenges. They are developed from the bone marrow-derived progenitors to complete their differentiation and maturation in the tissues where they eventually establish residence. MCs have been implicated in many diseases, such as allergy, parasitic infection, and neoplastic disorders. Immortalized MC lines, such as RBL-2H3, HMC-1, and LAD-2, are useful for investigating the biological functions of MC only to some extents due to the restriction of degranulation evaluation, in vivo injection and other factors. Over the past few decades, technologies for acquiring primarily MCs have been continually optimized, and novel protocols have been proposed. However, no relevant publications have analyzed and summarized these techniques. In this review, the classical approaches for extracting MCs are generalized, and new methods with potential values are introduced. We also evaluate the advantages and applicability of diverse MC models. Since MCs exhibit substantial plasticity and functional diversity due to different origins, it is both necessary and urgent to select a reliable and suitable source of MCs for a particular study.

Influence of Ship Emissions on Urban Air Quality: A Comprehensive Study Using Highly Time-Resolved Online Measurements and Numerical Simulation in Shanghai.

Shanghai has become an international shipping center in the world. In this study, the multiyear measurements and the high resolution air quality model with hourly ship emission inventory were combined to determine the influence of ship emissions on urban Shanghai. The aerosol time-of-flight mass spectrometer (ATOFMS) measurements were carried out at an urban site from April 2009 to January 2013. During the entire sampling time, most of the half-hourly averaged number fractions of primary ship emitted particles varied between 1.0-10.0%. However, the number fraction could reach up to 50% during the ship plume cases. Ship-plume-influenced periods usually occurred in spring and summer. The simulation of Weather Research and Forecasting/Community Multiscale Air Quality model (WRF/CMAQ) with hourly ship emission inventory provided the highly time-resolved concentrations of ship-related air pollutants during a ship plume case. It showed ships could contribute 20-30% (2-7 µg/m3) of the total PM2.5 within tens of kilometers of coastal and riverside Shanghai during ship-plume-influenced periods. Our results showed that ship emissions have substantial contribution to the air pollution in urban Shanghai. The control measures of ship emission should be taken considering its negative environment and human health effects.

Dry Particulate Nitrate Deposition in China.

A limited number of ground measurements of dry particulate nitrate deposition (NO3-) makes it difficult and challenging to fully know the status of the spatial and temporal variations of dry NO3- depositions over China. This study tries to expand the ground measurements of NO3- concentrations at monitoring sites to a national scale, based on the Ozone Monitoring Instrument (OMI) NO2 columns, NO2 profiles from an atmospheric chemistry transport model (Model for Ozone and Related chemical Tracers, version 4, MOZART-4) and monitor-based sources, and then estimates the NO3- depositions on a regional scale based on an inferred model. The ground NO2 concentrations were first derived from NO2 columns and the NO2 profiles, and then the ground NO3- concentrations were derived from the ground NO2 concentrations and the relationship between NO2 and NO3- based on Chinese Nationwide Nitrogen Deposition Monitoring Network (NNDMN). This estimated dry NO3- depositions over China will be helpful in determining the magnitude and pollution status in regions without ground measurements, supporting the construction plan of environmental monitoring in future.

Spatial and Seasonal Dynamics of Ship Emissions over the Yangtze River Delta and East China Sea and Their Potential Environmental Influence.

The Yangtze River Delta (YRD) port cluster is one of five major port clusters in China and is home to Shanghai port, the largest port worldwide. In this study, an automatic identification system-based model was built to estimate the ship exhaust emissions in the YRD and the East China Sea within 400 km of the coastline. In 2010, the total emissions of SO2, NOX, and PM2.5 were 3.8 × 10(5) tonnes/yr, 7.1 × 10(5) tonnes/yr, and 5.1 × 10(4) tonnes/yr, respectively. More than 60% and 85% of the ship emissions occurred within 100 km and 200 km of the coastline, respectively. Ship emissions also showed distinct seasonal variability. The emission of SO2 and NOX by ships in hot spots, such as ports and vessel traffic hubs was much higher than that on land, with maximum SO2 and NOX intensities from ships that were 36 times and 17 times greater, respectively, than the maximal land-based emissions. The potential impact of ship emissions at six hot spots on the surrounding atmospheric environment was estimated with the HYSPLIT model. Our study demonstrated that ship emissions have an important impact on both the entire YRD region and on greater East China.

Molecular therapy of colorectal cancer: progress and future directions.

Colorectal cancer (CRC) remains one of the most common types of cancer and leading causes of cancer death worldwide. Although the introduction of cytotoxic drugs such as oxaliplatin, irinotecan and fluorouracil has improved the treatment of advanced CRC, the individual response to chemoradiotherapy varies tremendously from one patient to another. However, recent progress in CRC molecular therapies may provide new insight into the treatment of this disease. Currently, components of the EGFR, VEGF, Wnt and NF-kB pathways are the most important targets for CRC therapy. This review chronicles the development of molecular CRC therapies over the past few decades. We also provide an update on the current progress of research concerning the molecular pathways leading to CRC and discuss the possible implications for CRC therapy.

An update on miRNAs as biological and clinical determinants in colorectal cancer: a bench-to-bedside approach.

Colorectal carcinogenesis represents a sequential progression of normal colonic mucosa from adenoma to carcinoma. It has become apparent that miRNA deregulation contributes to the initiation and progression of colorectal cancer (CRC). These oncogenic or tumor-suppressive miRNAs interact with intracellular signaling networks and lead to alteration of cell proliferation, apoptosis, metastasis and even response to chemotherapeutic treatments. This article aims to review the cutting edge progress in the discovery of the role of novel mechanisms for miRNAs in the development of CRC. We will also discuss the potential use of miRNAs as biomarkers for early diagnosis and prognosis of CRC. Furthermore, with advancements in RNA delivery technology, it is anticipated that manipulation of miRNAs may offer an alternative therapy for CRC treatment.

miR-150 functions as a tumour suppressor in human colorectal cancer by targeting c-Myb.

Our previously published study documented a deregulation of the microRNA miR-150 in colorectal cancer. Here, we investigated further, in vitro and in vivo, the potential molecular mechanisms underlying the involvement of miR-150 in colorectal cancer, using the appropriate molecular biological methods. We report that miR-150 is a key regulator in the tumourigenesis and progression of colorectal cancer, by acting as a tumour suppressor targeting c-Myb. The current findings suggest that miR-150 may have important roles in the pathogenesis of colorectal cancer.

Fine-Grained Recognition With Learnable Semantic Data Augmentation.

Fine-grained image recognition is a longstanding computer vision challenge that focuses on differentiating objects belonging to multiple subordinate categories within the same meta-category. Since images belonging to the same meta-category usually share similar visual appearances, mining discriminative visual cues is the key to distinguishing fine-grained categories. Although commonly used image-level data augmentation techniques have achieved great success in generic image classification problems, they are rarely applied in fine-grained scenarios, because their random editing-region behavior is prone to destroy the discriminative visual cues residing in the subtle regions. In this paper, we propose diversifying the training data at the feature-level to alleviate the discriminative region loss problem. Specifically, we produce diversified augmented samples by translating image features along semantically meaningful directions. The semantic directions are estimated with a covariance prediction network, which predicts a sample-wise covariance matrix to adapt to the large intra-class variation inherent in fine-grained images. Furthermore, the covariance prediction network is jointly optimized with the classification network in a meta-learning manner to alleviate the degenerate solution problem. Experiments on four competitive fine-grained recognition benchmarks (CUB-200-2011, Stanford Cars, FGVC Aircrafts, NABirds) demonstrate that our method significantly improves the generalization performance on several popular classification networks (e.g., ResNets, DenseNets, EfficientNets, RegNets and ViT). Combined with a recently proposed method, our semantic data augmentation approach achieves state-of-the-art performance on the CUB-200-2011 dataset. Source code is available at https://github.com/LeapLabTHU/LearnableISDA.

Development and validation of a novel miRNA classifier as a prognostic signature for stage II/III colorectal cancer.

BACKGROUND: The TNM staging remains the gold standard for determining the prognosis of patients with colorectal cancer (CRC), which is inadequate at identifying the subset of high-risk stage II and III patients that have a high potential of developing tumor recurrence and may experience death. Emerging evidence indicates that not only microRNAs (miRNAs) play important functional role in CRC development but may serve as important disease biomarkers. In this study we aimed to develop a miRNA-based classifier as a prognostic signature for improving the clinical outcome of patients with stage II/III CRC. METHODS: We performed a systematic and comprehensive discovery step to identify differentially expressed miRNAs in CRC. We subsequently determined the prognostic relevance of these miRNAs in stage II/III patients using qRT-PCR and developed a miRNA-based classifier for predicting disease-free survival (DFS) in a clinical cohort (n=186). RESULTS: Based upon miRNA expression profiling studies, we identified a panel of 10 miRNAs which are consistently differentially expressed in CRC vs. normal tissues. By using cox proportional hazard models, we then developed 6-miRNA-classifier (miR-183, -20a, -21, -195, -139 and -20a) to predict prognosis in clinical cohort, that had significantly superior predictive performance compared to other clinicopathological factors, and could successfully identify high-risk stage II and III CRC patients with poor prognosis [hazard ratio (HR) =2.16; P=0.0048]. In a multivariate analysis, this miRNA-based classifier emerged as an independent prognostic signature for poor DFS. CONCLUSIONS: Our miRNA-based classifier is a reliable predictive tool for determining prognosis in patents with stage II/III CRC, and might be able to identify high-risk patients that are candidates for more targeted personalized clinical management and surveillance.

Short-term in vitro culture of purity and highly functional rat bone marrow-derived mast cells.

Mast cells (MCs) are responsible for the innate immune response. Rat MCs are more suitable than mouse MCs as models of specific parasite infection processes and ovalbumin-induced asthma. Rat peritoneum-derived MCs and RBL-2H3 cells (an MC cell line) are widely used in disease studies. However, the application of rat bone marrow-derived MCs (BMMCs) are poorly documented in terms of the methodology of rat BMMC isolation. Here, we describe a relatively rapid, efficient, and simple method for the cultivation of rat BMMCs. As compared to previous protocols, rat BMMCs produced with the proposed protocol exhibited advantages in differentiation, proliferation, lifespan, and functionality, which should prove useful for studies of mucosal MC diseases in specific rat models.

Mast cells are essential intermediaries in regulating IL-33/ST2 signaling for an immune network favorable to mucosal healing in experimentally inflamed colons.

Mast cells (MCs) are potent tissue-resident immune cells that are distributed in the intraepithelial space of the intestine and have been implicated in regulating immune homeostasis and coordinating epithelial responses in inflamed mucosa of inflammatory bowel disease (IBD). IL-33 functions as an endogenous danger signal or alarmin in inflamed intestine segments. MCs highly express the IL-33 receptor ST2. However, the mechanisms underlying the immune regulation of MC-dependent IL-33/ST2 signaling at the barrier surface of the intestine remain largely unknown. We confirmed that MCs are required for the effective resolution of tissue damage using an experimental colitis model that allows for conditional ablation of MCs. After elucidating the IL-33 signaling involved in MC activity in the context of intestinal inflammation, we found that the function of restricted IL-33/ST2 signaling by MCs was consistent with an MC deficiency in response to the breakdown of the epithelial barrier. We observed that a tissue environment with a spectrum of protective cytokines was orchestrated by MC-dependent IL-33/ST2 signaling. Given the significant downregulation of IL-22 and IL-13 due to the loss of MC-dependent IL-33/ST2 signaling and their protective functions in inflammation settings, induction of IL-22 and IL-13 may be responsible for an immune network favorable to mucosal repair. Collectively, our data showed an important feedback loop in which cytokine cues from damaged epithelia activate MCs to regulate tissue environments essential for MC-dependent restoration of epithelial barrier function and maintenance of tissue homeostasis.

The effect of perioperative probiotics treatment for colorectal cancer: short-term outcomes of a randomized controlled trial.

This study was designed to mainly evaluate the anti-infective effects of perioperative probiotic treatment in patients receiving confined colorectal cancer (CRC) respective surgery. From November 2011 to September 2012, a total of 60 patients diagnosed with CRC were randomly assigned to receive probiotic (n = 30) or placebo (n = 30) treatment. The operative and post-operative clinical results including intestinal cleanliness, days to first - flatus, defecation, fluid diet, solid diet, duration of pyrexia, average heart rate, length of intraperitoneal drainage, length of antibiotic therapy, blood index changes, rate of infectious and non-infectious complications, postoperative hospital stay, and mortality were investigated. The patient demographics were not significantly different (p > 0.05) between the probiotic treated and the placebo groups. The days to first flatus (3.63 versus 3.27, p = 0.0274) and the days to first defecation (4.53 versus 3.87, p = 0.0268) were significantly improved in the probiotic treated patients. The incidence of diarrhea was significantly lower (p = 0.0352) in probiotics group (26.67%, 8/30) compared to the placebo group (53.33%, 16/30). There were no statistical differences (p > 0.05) in other infectious and non-infectious complication rates including wound infection, pneumonia, urinary tract infection, anastomotic leakage, and abdominal distension. In conclusion, for those patients undergoing confined CRC resection, perioperative probiotic administration significantly influenced the recovery of bowel function, and such improvement may be of important clinical significance in reducing the short-term infectious complications such as bacteremia.