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Retinoblastoma is a childhood retinal tumour that is the most common primary malignant intraocular tumour. However, it has been challenging to identify the cell types associated with genetic complexity. Here, we performed single-cell RNA sequencing on 14,739 cells from two retinoblastoma samples to delineate the heterogeneity and the underlying mechanism of retinoblastoma progression. Using a multiresolution network-based analysis, we identified two major cell types in human retinoblastoma. Cell trajectory analysis yielded a total of 5 cell states organized into two main branches, and the cell cycle-associated cone precursors were the cells of origin of retinoblastoma that were required for initiating the differentiation and malignancy process of retinoblastoma. Tumour cells differentiation reprogramming trajectory analysis revealed that cell-type components of multiple tumour-related pathways and predominantly expressed UBE2C were associated with an activation state in the malignant progression of the tumour, providing a potential novel “switch gene” marker during early critical stages in human retinoblastoma development. Thus, our findings improve our current understanding of the mechanism of retinoblastoma progression and are potentially valuable in providing novel prognostic markers for retinoblastoma.

PurposeTo explore the risk factors for ophthalmic artery (OA) stenosis and occlusion after intra-arterial chemotherapy (IAC) with selective ophthalmic artery catheterisation (OAC) in the treatment of retinoblastoma.DesignRetrospective, single centre case-control study.MethodsThe study was conducted including consecutive patients with unilateral or bilateral intraocular retinoblastoma undergoing IAC between June 2016 and June 2019 with a follow-up time of 4 years. Main outcomes are rate of IAC-induced OA occlusion and OA diameter.Results346 attempted OAC infusions were successful. The total incidence of OA occlusion was 15.89%. The occlusion and control groups were similar in patients’ age, sex and disease stage. Median OA diameter was 0.49 mm in those with OA occlusion, and 0.66 mm in those without occlusion. In the occlusion group, the OA diameter difference was significantly larger between the first IAC and the final IAC (0.22mm vs 0.12mm, p=0.001). In both groups, the median number of IAC treatments was 3. Multivariate Cox regression models included initial OA diameter (OR: 0.005, p=0.001), ratio of OA orifice diameter differences between first and last IAC to the initial OA orifice diameter (OR: 4.661, p=0.003), and number of IAC (OR: 1.538, p=0.042) as clinical features significantly associated with OA occlusion.ConclusionsThe OA diameter at first IAC treatment, the ratio of OA orifice diameter differences between first and last IAC to the initial OA orifice diameter and total number of IAC treatments may be three main clinical predictors for OA occlusion after IAC for retinoblastoma.

Landscape plants have both ecological and aesthetic value and may also represent ideal candidates for phytoremediation. In the present study, one round of hydroponic culture for 14 days with different cadmium (Cd) concentrations (0, 0.5, 1, and 2 mg L-1 Cd) was carried out to test whether Hydrocotyle vulgaris L. is a Cd-tolerant plant. Furthermore, physiological parameters, including pigment concentrations, photosynthesis, antioxidant enzyme activities (AEAs), and nutrient uptake, were also examined to determine the tolerance of H. vulgaris to Cd exposure. The results showed that H. vulgaris could grow normally under all Cd supply levels. The Cd removal efficiency reached 100% at Cd concentrations ≤1.0 mg L-1. The concentrations of Cd in roots and shoots increased (P < 0.05) with Cd supplementation. The maximum concentrations of Cd reached 26.4 and 118 mg kg-1 in shoots and roots, respectively. The translocation factor values were similar under all Cd treatments. The highest mean daily increase in biomass (MDIB) was obtained under 1 mg L-1 Cd exposure, which increased by 69.86% compared to that in the control, which may be due to the increased photosynthetic pigments, photosynthetic rate, and the consistent nutrient concentrations under this Cd level, as there were positive relationships between these parameters and MDIB. Moreover, the activities of AEA also generally explicated highest among all Cd levels. All these results indicate that the above physiological parameters play a positive role in promoting plant growth and alleviating Cd stress. In summary, H. vulgaris was verified as a potential Cd-tolerant plant, providing new information for Cd phytoremediation. Furthermore, given its extensive habitat distribution, this species might be tested for phytoremediation of contaminated soils in future work.

The current pandemic of COVID-19 has brought certain difficulties to the detection and diagnosis. With the continuous development of medical imaging technology, chest radiograph has become a common examination method for detecting lung diseases. Reasonable use of new coronary pneumonia chest radiographs and machine learning related algorithms to achieve efficient, accurate and automatic identification of covid-19 is extremely important. Based on the detection of four types of COVID-19, this paper proposes a method for the detection and classification of COVID-19 based on the YOLOv5 model. Experimental results show that our algorithm has the best performance compared with other deep learning algorithms. Specifically, the map@0.5 index of the prediction result of our algorithm model is 0.605, which is 32.096% and 18.627% larger than the Fast RCNN algorithm and the Efficient Net model respectively.

Atherosclerosis is a major pathology for cardiovascular diseases (CVDs). Clinically, the intermittent fasting (IF) has been observed to reduce the risk of CVDs. However, the effect of IF on the development of atherosclerosis has not been fully elucidated. Herein, we determined the protection of IF against high-fat diet–induced atherosclerosis in pro-atherogenic low-density lipoprotein receptor deficient (LDLR-/-) mice and the potentially involved mechanisms. The LDLR-/- mice were scheduled intermittent fasting cycles of 3-day HFD feeding ad libitum and 1 day fasting, while the mice in the control group were continuously fed HFD. The treatment was lasted for 7 weeks (∼12 cycles) or 14 weeks (∼24 cycles). Associated with the reduced total HFD intake, IF substantially reduced lesions in the en face aorta and aortic root sinus. It also increased plaque stability by increasing the smooth muscle cell (SMC)/collagen content and fibrotic cap thickness while reducing macrophage accumulation and necrotic core areas. Mechanistically, IF reduced serum total and LDL cholesterol levels by inhibiting cholesterol synthesis in the liver. Meanwhile, HFD-induced hepatic lipid accumulation was attenuated by IF. Interestingly, circulating Ly6Chigh monocytes but not T cells and serum c-c motif chemokine ligand 2 levels were significantly reduced by IF. Functionally, adhesion of monocytes to the aortic endothelium was decreased by IF via inhibiting VCAM-1 and ICAM-1 expression. Taken together, our study indicates that IF reduces atherosclerosis in LDLR-/- mice by reducing monocyte chemoattraction/adhesion and ameliorating hypercholesterolemia and suggests its potential application for atherosclerosis treatment.

Two Cd(II) coordination polymers namely, [Cd(L)(phen)(H2O)]n (1) and [Cd(L)(bpe)0.5]n (2) (H2L is 4,4′-{[1,2-phenylenebis-(methylene)]}bis(oxy)dibenzoic acid, bpe is 1,2-bis(-4-pyridyl)ethane and phen is 1,10-phenanthroline), have been created by the mixed-ligand self-assembly strategy. Moreover, the two compounds’ luminescent and photocatalytic performances were also studied. The treatment activity and nursing application values on children bronchopneumonia was explored and specific mechanism was investigated simultaneously. First of all, the ELISA detection kit was implemented to detect the TNF-α and IL-6 levels released into the respiratory secretions after treatment of compound. Furthermore, the real time RT-PCR was conducted to determine the activation levels of NF-κb signaling pathway in the airway epithelial cells. Finally, the cytotoxicity of the coordination polymers on normal airway epithelial cells was assessed through the CCK-8 assay.

Purpose: To evaluate the efficacy of an external carotid artery (ECA) alternative route in intra-arterial chemotherapy (IAC) for treatment of retinoblastoma.Methods: In this retrospective, single-centre, case-control study, 98 retinoblastoma patients who received successful IAC were included. The drug delivery routes were the primary ophthalmic artery (OA) route and the ECA route when OA catheterization was not feasible.Results: A total of 337 successful IAC procedures were performed in our study, of which 32 (9.5%) procedures were performed through the ECA route. Eighteen eyes (18.4%) accepted at least one IAC through branches of the ECA. Statistical analysis showed that there was no significant difference in ocular clinical results (enucleation, death, recurrence and event-free) between the ECA and OA routes. No significant association was found between the route of drug delivery and the ocular survival time (p = 0.69). The use of ECA catheterization in at least one IAC cycle was not a predictor of enucleation (HR: 1.58; 95% CI: 0.56–4.46, p = 0.39). The increasing number of procedures through the ECA route did not increase the risk of enucleation (HR: 1.64; 95% CI: 0.42–6.39, p = 0.48).Conclusion: The ECA alternative route did not affect the efficacy of IAC in retinoblastoma. When the standard OA approach is not feasible, ECA system catheterization should be considered.

Background Polyps may develop into colorectal cancer (CRC) after 10-20 years. The occurrence of polyps and tumors caused by somatic gene mutations is considered a main pathogenesis of CRC. Among all general patients with polyps or CRC, some had adenoma of varying degrees that were consistent with familial colorectal adenomas. A patient with CRC (the propositus) and his brothers and sister, all of whom had varying degrees of colorectal polyps showed different adenomas with different members in a family. Methods In the present study, a total of 9 family members were investigated, and a family tree was drawn. Genomic DNA was extracted from peripheral venous blood samples from family members, and whole-exome sequencing (WES) and Sanger sequencing were performed on the DNA samples. The result of WES was compared with compared directly to the reference genome (hg19) with Burrows-Wheeler Aligner, which is as control group from. Results We identified a base substitution in the miR-4477b gene (c.68415368T>G, chromosome 9 q13), predicted the target gene of miR-4477b through the biologic website, and analyzed the Gene Ontology (GO) and signal pathway of the target gene. The GO functional annotation analysis of the target gene of mir4477b revealed that these genes are involved mainly in the G1/S transition of the mitotic cell cycle, activation of mitogen-activated protein kinase activity, protein phosphorylation, and membrane, centrosome, cytoplasm, zinc ion-binding, protein-binding, and ligase activity. Kyoto Encyclopedia of Gene and Genomes pathway analysis revealed that miR-4477b regulates target genes mainly involved in the phosphoinositide 3-kinase/Akt signaling pathway, regulation of the actin cytoskeleton, proteoglycans in cancer, pathways in cancer, and renal cell carcinoma. Conclusions The mutation of the has-mir-4477b gene likely leads to the occurrence of adenoma and CRC. In-depth studies of patients from the same family with different stages of adenoma can avoid errors caused by gene diversity, incomplete clinical data, and uncertain disease development. The has-mir-4477b gene may represent a key gene mutation in colorectal carcinogenesis and a multiyear cancer risk for patients that requires further attention.

Motivation: Microsatellite instability (MSI) is a promising biomarker for cancer prognosis and chemosensitivity. Techniques are rapidly evolving for the detection of MSI from tumor-normal paired or tumor-only sequencing data. However, tumor tissues are often insufficient, unavailable, or otherwise difficult to procure. Increasing clinical evidence indicates the enormous potential of plasma circulating cell-free DNA (cfNDA) technology as a noninvasive MSI detection approach. Results: We developed MSIsensor-ct, a bioinformatics tool based on a machine learning protocol, dedicated to detecting MSI status using cfDNA sequencing data with a potential stable MSIscore threshold of 20%. Evaluation of MSIsensor-ct on independent testing datasets with various levels of circulating tumor DNA (ctDNA) and sequencing depth showed 100% accuracy within the limit of detection (LOD) of 0.05% ctDNA content. MSIsensor-ct requires only BAM files as input, rendering it user-friendly and readily integrated into next generation sequencing (NGS) analysis pipelines. Availability: MSIsensor-ct is freely available at https://github.com/niu-lab/MSIsensor-ct. Supplementary information: Supplementary data are available at Briefings in Bioinformatics online.

BackgroundLong non-coding RNAs (lncRNAs) have been identified as important epigenetic regulators that play critical roles in human cancers. However, the regulatory functions of lncRNAs in tumorigenesis remains to be elucidated. Here, we aimed to investigate the molecular mechanisms and potential clinical application of a novel lncRNA, retinoblastoma associated transcript-1 (RBAT1), in tumorigenesis.MethodsRBAT1 expression was determined by real-time PCR in both retinoblastoma (Rb) and bladder cancer (BCa) cell lines and clinical tissues. Chromatin isolation using RNA purification (ChIRP) assays were performed to identify RBAT1-interacting proteins. Patient-derived xenograft (PDX) retinoblastoma models were established to test the therapeutic potential of RBAT1-targeting GapmeRs.ResultsHere, we found that RBAT1 expression was significantly higher in Rb and BCa tissues than that in adjacent tissues. Functional assays revealed that RBAT1 accelerated tumorigenesis both in vitro and in vivo.Mechanistically, RBAT1 recruited HNRNPL protein to E2F3 promoter, thereby activating E2F3 transcription. Therapeutically, GapmeR-mediated RBAT1 silencing significantly inhibited tumorigenesis in orthotopic xenograft retinoblastoma models derived from Rb cell lines and Rb primary cells.ConclusionsRBAT1 overexpression upregulates a known oncogene, E2F3, via directly recruiting HNPNPL to its promoter and cis-activating its expression. Our finding provides a novel mechanism of lncRNA biology and provides potential targets for diagnosis and treatment of Rb and BCa.

Skin problems not only injure physical health but also induce psychological problems, especially for patients whose faces have been damaged or even disfigured. Using smart devices, most of the people are able to obtain convenient clinical images of their face skin condition. On the other hand, the convolutional neural networks (CNNs) have achieved near or even better performance than human beings in the imaging field. Therefore, this paper studied different CNN algorithms for face skin disease classification based on the clinical images. First, from Xiangya-Derm, which is, to the best of our knowledge, China's largest clinical image dataset of skin diseases, we established a dataset that contains 2656 face images belonging to six common skin diseases [seborrheic keratosis (SK), actinic keratosis (AK), rosacea (ROS), lupus erythematosus (LE), basal cell carcinoma (BCC), and squamous cell carcinoma (SCC)]. We performed studies using five mainstream network algorithms to classify these diseases in the dataset and compared the results. Then, we performed studies using an independent dataset of the same disease types, but from other body parts, to perform transfer learning on our models. Comparing the performances, the models that used transfer learning achieved a higher average precision and recall for almost all structures. In the test dataset, which included 388 facial images, the best model achieved 92.9%, 89.2%, and 84.3% recalls for the LE, BCC, and SK, respectively, and the mean recall and precision reached 77.0% and 70.8%.

Objectives. To evaluate CNN models’ performance of identifying the clinical images of basal cell carcinoma (BCC) and seborrheic keratosis (SK) and to compare their performance with that of dermatologists. Methods. We constructed a Chinese skin diseases dataset which includes 1456 BCC and 1843 SK clinical images and the corresponding medical history. We evaluated the performance using four mainstream CNN structures and transfer learning techniques. We explored the interpretability of the CNN model and compared its performance with that of 21 dermatologists. Results. The fine-tuned InceptionResNetV2 achieved the best performance, with an accuracy and area under the curve of 0.855 and 0.919, respectively. Further experimental results suggested that the CNN model was not only interpretable but also had a performance comparable to that of dermatologists. Conclusions. This study is the first on the assistant diagnosis of BCC and SK based on the proposed dataset. The promising results suggested that CNN model’s performance was comparable to that of expert dermatologists.

Motivation HotSpot3D is a widely used software for identifying mutation hotspots on the 3D structures of proteins. To further assist users, we developed a new HotSpot3D web server to make this software more versatile, convenient and interactive. Results The HotSpot3D web server performs data pre-processing, clustering, visualization and log-viewing on one stop. Users can interactively explore each cluster and easily re-visualize the mutational clusters within browsers. We also provide a database that allows users to search and visualize proximal mutations from 33 cancers in the Cancer Genome Atlas. Availability and implementation http://niulab.scgrid.cn/HotSpot3D/. Supplementary information Supplementary data are available at Bioinformatics online.

Long non-coding RNAs (lncRNAs) have been identified as crucial regulators in many human cancers. Many lncRNAs show aberrant expression in cancer, and some of them play critical roles in tumor proliferation, invasion, and metastasis. However, the regulatory functions of lncRNAs in melanoma progression remain to be elucidated. We utilized the Real-time PCR methodology to determine the expression of LINC-PINT in melanoma cell lines. To evaluate the effect of LINC-PINT on tumorigenesis of melanoma, we used Cell Counting Kit-8 (CCK8) and colony formation assay. Flow cytometry assay was used to detect the function of LINC-PINT on cell cycle status. PINT-interacting proteins were identified by chromatin isolation using RNA purification (ChIRP). Microarray assay and bioinformatics analysis were used to find the potential target genes of LINC-PINT and the status of LINC-PINT target gene candidate was verified using chromatin immunoprecipitation assay (ChIP). LINC-PINT plays a role in suppressing the tumorigenicity of melanoma, which was further determined by xenograft model assay. LINC-PINT was significantly downregulated in melanoma tissues and cell lines. The overexpression of LINC-PINT in tumor cells resulted in significant tumor growth reduction and migration inhibition in A375, Mum2B and CRMM1 cells. Results based on the in vivo xenograft model were further consistent with the in vitro findings that LINC-PINT impeded growth and metastasis of melanoma cells. Microarray assay and bioinformatics analysis indicated that CDK1, CCNA2, AURKA, and PCNA were potential targets of LINC-PINT. In conclusion, LINC-PINT inhibits the tumorigenicity of melanoma through recruiting EZH2 to the promoter of its target genes, leading to H3K27 trimethylation and epigenetic silencing of target genes. LINC-PINT may serve as a novel diagnostic and therapeutic target for melanoma.

Precisely predicting the required pre-surgery blood volume (PBV) in surgical patients is a formidable challenge in China. Inaccurate estimation is associate with excessive costs, postponed surgeries and adverse outcome after surgery due to in sufficient supply or inventory. This study aimed to predict required PBV based on machine learning techniques. 181,027 medical documents over 6 years were cleaned and finally obtained 92,057 blood transfusion records. The blood transfusion and surgery related factors of perioperative patients, surgeons experience volumes and the actual volumes of transfused RBCs were extracted. 6 machine learning algorithms were used to build prediction models. The surgery patients received allogenic RBCs or without transfusion, had total volume less than 10 units, or had the latest laboratory examinations of pre-surgery within 7 days were included, providing 118,823 data points. 39 predictive factors related to the RBCs transfusion were identified. Random forest model was selected to predict the required PBV of RBCs with 72.9% accuracy and strikingly improved the accuracy by 30.4% compared with surgeons experience, where 90% of data was used for training. We tested and demonstrated that both the data-driven models and the random forest model achieved higher accuracy than surgeons experience. Furthermore, we developed a computational tool, PTRBC, to precisely estimate the required PBV in surgical patients and we believe this tool will find more applications in assisting clinician decisions, not only confined to making accurate pre-surgery blood requirement predicting.

According to diagnostic criteria, skin tumors can be divided into three categories: benign, low degree and high degree malignancy. For high degree malignant skin tumors, if not detected in time, they can do serious harm to patients' health. However, in clinical practice, identifying malignant degree requires biopsy and pathological examination which is time costly. Furthermore, in many areas, due to the severe shortage of dermatologists, it's inconvenient for patients to go to hospital for examination. Therefore, an easy to access screening method of malignant skin tumors is needed urgently. Firstly, we spend 5 years to build a dataset which includes 4,500 images of 10 kinds of skin tumors. All instances are verified pathologically thus trustworthy; Secondly, we label each instance to be either low-risk, high-risk or dangerous in which Junctional nevus, Intradermal nevus, Dermatofibroma, Lipoma and Seborrheic keratosis are low-risk, Basal cell carcinoma, Bowen's disease and Actinic keratosis are high-risk, Squamous cell carcinoma and Malignant melanoma are dangerous; Thirdly, we apply the Xception architecture to build the risk degree classifier. The area under the curve (AUC) for three risk degrees reach 0.959, 0.919 and 0.947 respectively. To further evaluate the validity of the proposed risk degree classifier, we conduct a competition with 20 professional dermatologists. The results showed the proposed classifier outperforms dermatologists. Our system is helpful to patients in preliminary screening. It can identify the patients who are at risk and alert them to go to hospital for further examination.

Previous studies including ours demonstrated that methyl-CpG–binding domain 2 (MBD2) acts as a reader to decipher DNA methylome-encoded information. We thus in the current study used Mbd2−/− mice as a model to dissect the impact of high-fat diet (HFD) on DNA methylome relevant to the pathoetiology of obesity. It was interestingly noted that mice deficient in Mbd2 were protected from HFD-induced obesity and insulin resistance. Mechanistic study revealed that HFD rendered epididymal adipose tissues to undergo a DNA methylation turnover as evidenced by the changes of methylation levels and patterns. Specifically, HFD was noted with higher potency to induce DNA hypomethylation in genes relevant to energy storage than that in genes associated with energy expenditure. As a result, arrays of genes were subjected to expression changes, which led to an altered homeostasis for energy storage and expenditure in favor of obesity development. Loss of Mbd2 resulted in impaired implementation of above DNA methylation changes associated with altered energy homeostasis, which then protected mice from HFD-induced obesity and insulin resistance. Those data would provide novel insight into the understanding of the pathoetiology underlying obesity with potential for developing effective therapies against obesity in clinical settings.

Kinesins are a superfamily of motor proteins and are often dysregulated in many cancers. KIF15, which belongs to the kinesin-12 family, has been shown to function in many different cellular processes, including proliferation, apoptosis, differentiation and development. However, the role of KIF15 in melanoma, remains unknown. In this study, the expression levels of KIF15 in melanoma cells lines and tissues were determined via real-time PCR, immunohistochemical staining and western blot. The effect of KIF15 on tumorigenesis was evaluated by using MTT and colony information. The function of KIF15 on cell survival was detected through flow cytometry assay. Microarray assay and bioinformatics analysis were used to find the potential target of KIF15. We show that KIF15 was significantly upregulated in melanoma cells and tissues. The suppression of KIF15 in tumors significantly reduced tumor growth and increased apoptosis in A375 and OCM1 cells. Findings based on the subcutaneous xenograft model were further consistent with the in vitro results that KIF15 knockdown inhibited melanoma tumor growth in vivo. Microarray assay and bioinformatics indicated that BIRC5, CDK4 and WNT5A were three potential targets of KIF15. Taken together, our results suggest that KIF15 plays a positive role in the tumorigenicity of melanoma and it may serve as a novel diagnostic and therapeutic target for melanoma, especially uveal melanoma.

Background: Recurrent eyelid sebaceous carcinoma (SC) after primary resection still remains a great challenge for ophthalmologists. The predictors of recurrence are multifactorial, the identification of core risk factors to construct an individualized prediction model is warranted. The purpose of this study is to develop and validate a nomogram for individualized recurrence prediction of eyelid SC and to determine the independent risk factors. Methods: A multicenter cohort study. The study included 418 consecutive patients with eyelid SC, and this sample was divided into training (n=293) and validation cohorts (n=125). Least absolute shrinkage and selection operator (LASSO) regression was applied to select the features for the nomogram. The model was evaluated using the receiver operating characteristic (ROC)-derived area under the curve (AUC), calibration plot, and decision-curve analyses (DCAs), and it was compared with the TNM staging system. These results were externally validated with bootstrap resampling in an independent cohort. Multivariate Cox regression was used to explore the independent predictors of recurrence. Findings: This nomogram displayed satisfactory discriminative ability and good calibration for both the training (C-index: 0.83; AUC: 0.84) and validation (C-index: 0.80; AUC: 0.82) cohorts. The discriminative ability compared significantly favorable than TNM staging (C-index: training cohort: 0.67, validation cohort: 0.71; AUC: training cohort: 0.67, validation cohort: 0.71; all p

Background: The prognosis of Chinese patients with eyelid sebaceous gland carcinoma (SC) has not been updated for more than 3 decades. The predictors for the prognoses are multifactorial, there is no validated prognostic model for eyelid SC. Methods: The study included 238 consecutive patients with eyelid SC. All patients were followed up for metastasis and mortality. The predictors of tumor-related survival were explored by Cox analyses. A prognostic nomogram was developed and validated using bootstrap resampling. The predictive accuracy and discriminative ability were compared between nomogram and Tumor, Node, Metastasis (TNM) staging system. Findings: After a median follow-up period of 55.5 months, 27 (11.3%) patients died of the metastatic SC, with a median survival time of 48.0 months. The 5-year and 10-year tumor-related survival rate was 88.1% and 77.9%, respectively. Prior radiation therapy (HR:5.63, p=0.003), tumor with orbital involvement (HR:4.64, p=0.001), greatest tumor basal diameter (HR:1.07, p

Background MicroRNAs (miRNAs) have been shown to function in many different cellular processes, including proliferation, apoptosis, differentiation and development. miR-181a, -181b, -181c and -181d are miR-181 members of the family, which has been rarely studied, especially uveal melanoma. Methods The expression level of miR-181 family in human uveal melanoma cell lines was measured via real-time PCR (RT-PCR). The function of miR-181 on cell cycle was detected through Flow Cytometry assay. Microarray assay and Bioinformatics analysis were used to find the potential target of miR-181b, and dual-luciferase reporter assays further identified the target gene. Results MiR-181 family members were found to be highly homologous across different species and their upregulation significantly induces UM cell cycle progression. Of the family members, miR-181b was significantly overexpressed in UM tissues and most UM cells. Bioinformatics and dual luciferase reporter assay confirmed CTDSPL as a target of miR-181b. miR-181b over-expression inhibited CTDSPL expression, which in turn led to the phosphorylation of RB and an accumulation of the downstream cell cycle effector E2F1, promoting cell cycle progression in UM cells. Knockdown CTDSPL using siRNAs showing the same effect, including increase of E2F1 and the progression of cell cycle. Conclusions MiR-181 family members are key negative regulators of CTDSPL-mediated cell cycle progression. These results highlight that miR-181 family members, especially miR-181b, may be useful in the development of miRNA-based therapies and may serve as novel diagnostic and therapeutic candidate for UM. Electronic supplementary material The online version of this article (10.1186/s13046-018-0679-5) contains supplementary material, which is available to authorized users.

The objectives of this epidemiological study were to evaluate the prevalence of farmer's lung disease (FLD) and to explore the potential risk factors for FLD among Chinese greenhouse farmers. A total of 835 plastic film greenhouses, including 5,880 active farmers who engaged in crop cultivation or poultry farming, were randomly selected from the rural regions of Northeastern China. These farmers participated in the study by answering a medical questionnaire. 5,420 greenhouse farmers accepted and answered questionnaires in full (response rate, 92.18 %). Prevalence of FLD among these farmers was 5.7 % (308/5,420). Besides, a number of classic risk factors for FLD were identified, such as years of age, shorter time interval for re-entry greenhouse, ventilation frequency of greenhouse more than once per 4 h, the area of greenhouses greater than 30 m(2) but without a ventilation facility, ventilation duration less than 30 min every time, greenhouse with height less than 1.8 m, greenhouse with humidity greater than 65 %, frequent exposure to moldy materials in greenhouse, living inside greenhouse, and et al. FLD is and will continue to be a real health problem for Chinese farmers. If these preventive measures are implemented, the prevalence of FLD in Chinese greenhouse farmers might be greatly reduced.

In this paper we describe how utilization of low molecular weight alginate-derived oligosaccharide (ADO) and chito-oligosaccharide (COS) in conjunction with antibiotics, could more effectively inhibit the growth of wild-type and resistant Pseudomonas aeruginosa. Inhibition is effected by modulating the bacteria's quorum sensing (QS) system, thus regulating biofilm formation and reducing resistance to antibiotic treatment. This can be demonstrated by using conventional MIC screening. COS showed synergistic effects with azithromycin, whereas ADO indicated additive effects against wild-type P. aeruginosa. Using electrospray-ionization mass spectroscopy (ESI-MS), matrix-assisted laser desorption/ionization-time of flightmass spectroscopy (MALDI-TOF-MS) and nuclear magnetic resonance (NMR), the chemical structure of ADO and of COS was characterized. The wild-type and resistant strains were identified by 16S rRNA sequence analysis. This report demonstrates the feasibility of attenuating the tolerance of P. aeruginosa to azithromycin by using specific marine oligosaccharides.

It has been suggested that zinc may have a protective role against heart defects during fetal development. We investigated the effects of zinc on the development of fetal cardiac malformations induced by homocysteine. Pregnant Sprague-Dawley rats were randomized into one of five groups: control (C), homocysteine (H), homocysteine + zinc (Z), homocysteine + folic acid (F), or homocysteine + zinc + folic acid (ZF) (each n = 8). Homocysteine (8 nmol/day) was administered intraperitoneally in the H, Z, F, and ZF groups on gestation days (GD) 8, 9, and 10. Zinc (30 mg/kg day), folic acid (30 mg/kg day), or both (30 mg/kg day each) were administered intragastrically daily in the Z, F, and ZF groups, respectively, throughout the pregnancy. In each group, two fetuses were removed on GD 13, 15, 17, and 19 and examined for cardiac malformations; maternal copper/zinc-containing-superoxide dismutase (Cu/Zn-SOD) activity and metallothionein type I (MT-1) mRNA expression were measured simultaneously. The prevalence of cardiac malformations was significantly higher in group H than in group C, and significantly lower in group Z than in group H at the studied time points. Cu/Zn-SOD activity and MT-1 mRNA levels were significantly lower in group H than in group C, and significantly higher in group Z than in group H. Our data suggest that zinc antagonizes homocysteine-induced teratogenic effects on the fetal heart, possibly via the inhibition of excessive peroxidation.

C/EBP homologous protein (Chop) has been shown to have altered expression in patients with idiopathic pulmonary fibrosis (IPF), but its exact role in IPF pathoaetiology has not been fully addressed. Studies conducted in patients with IPF and Chop(-/-) mice have dissected the role of Chop and endoplasmic reticulum (ER) stress in pulmonary fibrosis pathogenesis. The effect of Chop deficiency on macrophage polarization and related signalling pathways were investigated to identify the underlying mechanisms. Patients with IPF and mice with bleomycin (BLM)-induced pulmonary fibrosis were affected by the altered Chop expression and ER stress. In particular, Chop deficiency protected mice against BLM-induced lung injury and fibrosis. Loss of Chop significantly attenuated transforming growth factor β (TGF-β) production and reduced M2 macrophage infiltration in the lung following BLM induction. Mechanistic studies showed that Chop deficiency repressed the M2 program in macrophages, which then attenuated TGF-β secretion. Specifically, loss of Chop promoted the expression of suppressors of cytokine signaling 1 and suppressors of cytokine signaling 3, and through which Chop deficiency repressed signal transducer and activator of transcription 6/peroxisome proliferator-activated receptor gamma signaling, the essential pathway for the M2 program in macrophages. Together, our data support the idea that Chop and ER stress are implicated in IPF pathoaetiology, involving at least the induction and differentiation of M2 macrophages.

Aims We randomly sampled a community-based, healthy population to evaluate the prevalence and associated risk factors of overactive bladder (OAB) syndrome by using the International Continence Society (ICS) definition. Methods We randomly sampled 6,066 women (3.0% of registered female residents aged 20 years and older in Fuzhou) and mailed Bristol Female Lower Urinary Tract Symptoms questionnaire for women self-completion. Women (4,684; 77.2%) with evaluable data were included in this study. Results The prevalence of OAB was 8.0% (n = 377), OABdry 2.4% (n = 114), and OABwet 5.6% (n = 263), hence 30% had OABdry and 70% OABwet. The prevalence of OAB and OABwet demonstrated an significant increasing with advancing age (P 2, constipation, episiotomy, and higher BMI were potential risk factors for OAB, constipation increased the occurrence of OABdry. OABwet was associated with menopause, parity >2, higher fetal birthweight, episiotomy, while cesarean delivery protected against the development of OABwet. Conclusions The prevalence of OAB in chinese women is lower than that of most reports in Occidental women, and increases with advancing age. Many potential risk factors increase the occurrence of OAB. Neurourol. Urodynam. 25:717–721, 2006. © 2006 Wiley-Liss, Inc.

Previous studies including ours demonstrated that methyl-CpG-binding domain 2 (MBD2) acts as a reader to decipher DNA methylome-encoded information. We thus in the current study used Mbd2

Zinc has been implicated to have a protective role against heart malformations during fetal development. Metallothionein 1 (MT-1) and zinc transporter 1 (ZnT-1) are two major metabolic factors that are associated with zinc metabolism. The present work aimed to investigate the association of placental MT-1 and ZnT-1 expressions with fetal heart malformations resulting from maternal zinc deficiency. Sprague–Dawley female rats were randomly divided into five groups of extremely low-zinc, low-zinc, moderately low-zinc, marginally low-zinc and normal zinc (n = 9–12), and were fed diets with controlled zinc content at 1.0 ± 0.3, 8.4 ± 1.8, 15.4 ± 2.8, 22.4 ± 4.1 and 29.4 ± 5.3 [mean ± standard deviation (SD)] mg of zinc/kg, respectively, from day 25 of preconception until day 19 of gestation. The female rats were bred, their fetuses were harvested at day 19 of gestation after killing the dams, and fetal hearts were morphologically examined. Zinc concentration and alkaline phosphatase (ALP) activity in maternal venous blood sera were tested, and MT-1 and ZnT-1 mRNA expressions in the placenta were assayed. Zinc concentrations and ALP activities in the blood were low in all zinc-deficient diet groups in a dose-dependent fashion. The incidences of heart malformations were increased, and the levels of placental MT-1 and ZnT-1 mRNA expressions were decreased in the extremely low-zinc, low-zinc and moderately low-zinc groups compared with the normal zinc group. Specifically, mRNA levels of placental MT-1 or ZnT-1 were significantly decreased and were lower than the specific threshold values in the fetuses with heart malformations but not in the fetuses without heart malformations in all the groups. These data indicate that maternal zinc deficiency resulted in an elevated incidence of fetal heart malformations, which was associated with significant decreases in placental MT-1 and ZnT-1 mRNA expressions to the levels below the threshold values that may be a crucial factor to determine the presence of fetal heart malformations.

In the pursuit of a highly efficient high-rise structure, structural engineers have been developing new systems. Almost all of these techniques involve use of the entire width of the building. Legacy systems, such as outriggers, belt trusses, and perimeter braces, provide efficient systems, but they have an impact on the ductility, redundancy, and uniformity of the stiffness of structure. In regions of high seismic activity, the cost of adopting such legacy systems can be significant in terms of structural and architectural efficiency. The design team for Shum-Yip Tower One developed a structural system which allows for maximum architectural flexibility without compromising efficiency of the structure. This system has been named the Ladder System. The architectural requirement of unobstructed views has resulted in fewer perimeter columns. Gravity loads at the perimeter are directed through eight mega-columns; the resulting higher gravity loads have eliminated tension due to overturning. This gravity system is instrumental in the success of the Ladder System.

Background Despite decades of extensive studies, the morbidity and mortality for acute lung injury/acute respiratory distress syndrome (ALI/ARDS) remained high. Particularly, biomarkers essential for its early diagnosis and prognosis are lacking. Methods Recent studies suggest that alveolar macrophages (AMs) at the exudative phase of ALI/ARDS initiate, amplify and perpetuate inflammatory responses, while they resolve inflammation in the recovery phase to prevent further tissue injury and perpetuated inflammation in the lung. Therefore, proteins relevant to this functional switch could be valuable biomarkers for ALI/ARDS diagnosis and prognosis. We thus conducted comparative analysis of the AM proteome to assess its dynamic proteomic changes during ALI/ARDS progression and recovery. Results 135 proteins were characterized to be differentially expressed between AMs at the exudative and recovery phase. MALDI-TOF-MS and peptide mass fingerprint (PMF) analysis characterized 27 informative proteins, in which 17 proteins were found with a marked increase at the recovery phase, while the rest of 10 proteins were manifested by the significantly higher levels of expression at the exudative phase. Conclusions Given the role of above identified proteins played in the regulation of inflammatory responses, cell skeleton organization, oxidative stress, apoptosis and metabolism, they have the potential to serve as biomarkers for early diagnosis and prognosis in the setting of patients with ALI/ARDS.

Diffusion-weighted MRI (DWI) has been proposed as a method to evaluate the integrity of white matter tracts in the spinal cord. The integrity of the spinal cord reflects the exact stage of traumatic injury. The purpose of this study was to evaluate the diagnostic value of DWI in SCIWORA in the thoracic spine. A total of five patients with thoracic SCIWORA underwent MRI and DWI within 48 h of injury. DWIs were obtained with a single-shot fast spin-echo (SSFSE) sequence; TI- and T2-weighted images were obtained with spin echo. Consistency among the clinical presentation, outcome, MRI and DWI was analysed. There was complete injury in one patient and partial in four patients. Four patients showed hypointense T1-weighted signal and hyperintense T2-weighted signal, and one patient had no changes on MRI. All patients showed hyperintense signal on DWI. Two patients made good recoveries (ASIA grades D and E), one had a moderate recovery (ASIA grade C), and two showed minimal or no improvement (ASIA grade A or B) in neurological function. Patients with no cord changes on MRI showed abnormal signals on DWI. It is likely that in the future DWI may provide important information complimentary to conventional MRI and allow a better prognostic evaluation of recovery from SCIWORA.

The linkage between endometriosis and galactose-1-phosphate uridyl transferase gene (GALT) mutations is controversial. In this study, the prevalence of the most common GALT mutations, Q188R and N314D, was assessed in women with endometriosis in a Chinese population. Three hundred twenty five unrelated women with endometriosis were enrolled. Samples of umbilical cord blood obtained from 310 female newborn infants were used as population controls. Genomic DNA isolated from endometriosis patients and controls were subjected to multiple polymerase chain reactions to determine the Q188R and N314D mutations. There was no significant difference in the frequencies of the Q188R and N314D mutations between endometriosis patients and controls. The endometriosis patients were further divided into subgroups of stage III and IV disease, but still no statistically significant differences were observed in the frequency of the Q188R and N314D mutations between any of these groups and the controls. These findings suggest that Q188R and N314D mutations are not likely to be associated with an increased risk of endometriosis among Chinese Women. Environ. Mol. Mutagen., 2006 © 2006 Wiley-Liss, Inc.

Aims: To evaluate the prevalence and associated risk factors of lower urinary tract symptoms (LUTS). Methods: We randomly sampled 6066 women (3.0% of registered female residents aged 20 years and older in Fuzhou) and mailed Bristol Female Lower Urinary Tract Symptoms questionnaire to women for self-completion. 4684 (77.2%) women with evaluable data were included in this study. Results: The prevalence of LUTS, voiding symptoms, storage symptoms was 39.7%, 13.4%, 37.3%, respectively. Among voiding symptoms, the prevalence of hesitancy, slow stream, intermittence, straining, terminal dribble, splitting was 6.8%, 5.5%, 4.8%, 4.5%, 4.1%, 3.5%, respectively. Among storage symptoms, stress incontinence, urge incontinence, urgency, frequency, nocturia, enuresis was 16.6%, 10.0%, 10.2%, 16.4%, 9.9%, 3.9%, respectively. A multiple logistic regression analysis showed menopause, parity >2, constipation, fetal birthweight, and episiotomy were common potential risk factors for LUTS, voiding and storage symptoms. Higher BMI increased the occurrence of LUTS and storage symptoms, while cesarean delivery and labor protected against the development of storage symptoms. Conclusions: The prevalence of LUTS in Chinese women is lower than that of most reports in Occidental women. The prevalence of LUTS increases with age.