SLC11A1 promotes kidney renal clear cell carcinoma (KIRC) progression by remodeling the tumor microenvironment.

Kidney renal clear cell carcinoma (KIRC) is a highly immune-infiltrated kidney cancer with the highest mortality rate and the greatest potential for invasion and metastasis. Solute carrier family 11 member1 (SLC11A1) is a phagosomal membrane protein located in monocytes and plays a role in innate immunity, autoimmune diseases, and infection, but its expression and biological role in KIRC is still unknown. In this study, we sought to investigate the potential value of SLC11A1 according to tumor growth and immune response in KIRC. TIMER and UALCAN database was used to analyze the expression feature and prognostic significance of SLC11A1 and its correlation with immune-related biomarkers in KIRC. Proliferation, migration, and invasion were measured using colony formation, EdU, and transwell assays. Role of SLC11A1 on KIRC tumor growth was examined by the xenograft tumor model in vivo. Effects of KIRC cells on macrophage polarization and the proliferation and apoptosis of CD8+ T cells were analyzed using flow cytometry assays. Herein, SLC11A1 was highly expressed in KIRC tissues and cell lines. SLC11A1 downregulation repressed KIRC cell proliferation, migration, invasion, macrophage, and lymphocyte immunity in vitro, as well as hindered tumor growth in vivo. SLC11A1 is significantly correlated with immune cell infiltration and immune-related biomarkers. In KIRC patients, SLC11A1 is highly expressed and positively correlated with the immune-related factors CCL2 and PD-L1. SLC11A1 induced CCL2 and PD-L1 expression, thereby activating the JAK/STAT3 pathway. SLC11A1 deficiency constrained KIRC cell malignant phenotypes and immune response via regulating CCL2 and PD-L1-mediated JAK/STAT3 pathway, providing a promising therapeutic target for KIRC treatment.

Establishment and validation of a nomogram to select patients with metastatic sarcomatoid renal cell carcinoma suitable for cytoreductive radical nephrectomy.

Introduction: Metastatic renal cell carcinoma (mRCC) with sarcomatoid features has a poor prognosis. Cytoreductive radical nephrectomy (CRN) can improve prognosis, but patient selection is unclear. This study aimed to develop a prediction model for selecting patients suitable for CRN. Materials and methods: Patients with a diagnosis of mRCC with sarcomatoid features in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015 were retrospectively reviewed. CRN benefit was defined as a survival time longer than the median overall survival (OS) in patients who did not receive CRN. A prediction nomogram was established and validated using the SEER cohort (training and internal validation) and an external validation cohort. Results: Of 900 patients with sarcomatoid mRCC, 608 (67.6%) underwent CRN. OS was longer in the CRN group than in the non-CRN group (8 vs. 6 months, hazard ratio (HR) = 0.767, p = 0.0085). In the matched CRN group, 124 (57.7%) patients survived >6 months after the surgery and were considered to benefit from CRN. Age, T-stage, systematic therapy, metastatic site, and lymph nodes were identified as independent factors influencing OS after CRN, which were included in the prediction nomogram. The monogram performed well on the training set (area under the receiver operating characteristic (AUC) curve = 0.766, 95% confidence interval (CI): 0.687-0.845), internal validation set (AUC = 0.796, 95% CI: 0.684-0.908), and external validation set (AUC = 0.911, 95% CI: 0.831-0.991). Conclusions: A nomogram was constructed and validated with good accuracy for selecting patients with sarcomatoid mRCC suitable for CRN.

Realistic fault detection of li-ion battery via dynamical deep learning.

Accurate evaluation of Li-ion battery (LiB) safety conditions can reduce unexpected cell failures, facilitate battery deployment, and promote low-carbon economies. Despite the recent progress in artificial intelligence, anomaly detection methods are not customized for or validated in realistic battery settings due to the complex failure mechanisms and the lack of real-world testing frameworks with large-scale datasets. Here, we develop a realistic deep-learning framework for electric vehicle (EV) LiB anomaly detection. It features a dynamical autoencoder tailored for dynamical systems and configured by social and financial factors. We test our detection algorithm on released datasets comprising over 690,000 LiB charging snippets from 347 EVs. Our model overcomes the limitations of state-of-the-art fault detection models, including deep learning ones. Moreover, it reduces the expected direct EV battery fault and inspection costs. Our work highlights the potential of deep learning in improving LiB safety and the significance of social and financial information in designing deep learning models.

Development and validation of a prognostic model incorporating tumor thrombus grading for nonmetastatic clear cell renal cell carcinoma with tumor thrombus: A multicohort study.

There is significant variability with respect to the prognosis of nonmetastatic clear cell renal cell carcinoma (ccRCC) patients with venous tumor thrombus (VTT). By applying multiregion whole-exome sequencing on normal-tumor-thrombus-metastasis quadruples from 33 ccRCC patients, we showed that metastases were mainly seeded by VTT (81.8%) rather than primary tumors (PTs). A total of 706 nonmetastatic ccRCC patients with VTT from three independent cohorts were included in this study. C-index analysis revealed that pathological grading of VTT outperformed other indicators in risk assessment (OS: 0.663 versus 0.501-0.610, 0.667 versus 0.544-0.651, and 0.719 versus 0.511-0.700 for Training, China-Validation, and Poland-Validation cohorts, respectively). We constructed a risk predicting model, TT-GPS score, based on four independent variables: VTT height, VTT grading, perinephric fat invasion, and sarcomatoid differentiation in PT. The TT-GPS score displayed better discriminatory ability (OS, c-index: 0.706-0.840, AUC: 0.788-0.874; DFS, c-index: 0.691-0.717, AUC: 0.771-0.789) than previously reported models in risk assessment. In conclusion, we identified for the first-time pathological grading of VTT as an unheeded prognostic factor. By incorporating VTT grading, the TT-GPS score is a promising prognostic tool in predicting the survival of nonmetastatic ccRCC patients with VTT.

ROCK2-RNA interaction map reveals multiple biological mechanisms underlying tumor progression in renal cell carcinoma.

Renal cell carcinoma (RCC) is the most common form of kidney cancer in adults. Despite new therapeutic modalities, the outcomes for RCC patients remain unsatisfactory. Rho-associated coiled-coil forming protein kinase 2 (ROCK2) has previously been shown to be upregulated in RCC, and its expression was negatively correlated with patient survival. However, the precise molecular function of ROCK2 has remained unclear. Herein, using RNA-seq analysis of ROCK2 knockdown and control cells, we identified 464 differentially expressed genes, and 1287 alternative splicing events in 786-O RCC cells. Furthermore, mapping of iRIP-seq reads in 786-O cells showed a biased distribution at 5' UTR, intronic and intergenic regions. By comparing ROCK2-regulated alternative splicing and iRIP-seq data, we found 292 overlapping genes that are enriched in multiple tumorigenic pathways. Taken together, our work defined a complex ROCK2-RNA interaction map on a genomic scale in a human RCC cell line, which deepens our understanding of the molecular function of ROCK2 in cancer development.

A Retrospective Study of Clinical and Immunological Features of a Pediatric Population with Talaromyces marneffei Infection.

BACKGROUND: Talaromyces marneffei (T. Marneffei) infection is considered as an indicator of immunosuppression in immunocompromised individuals, leading to multiple organ damage. Our study aimed to evaluate both the clinical characteristics and immunological features of pediatric patients infected with T. marneffei from our institute, providing novel insights into diagnosis and treatment for this life-threatening disease. METHOD: Thirteen pediatric patients with T. marneffei infection were enrolled in Guangzhou Women and Children's Medical Center during 2012 to 2020. Clinical data and laboratory findings were collected and further analyzed. Pearson correlation coefficient was calculated to determine the relationship between serum immunoglobulins (Igs) levels and white blood cell count, or the absolute lymphocyte count. RESULTS: Patients were diagnosed as having T. Marneffei infection mainly based on the results of fungal culture and Gram stain of specimens. The most common presentations were fever (69%), pneumonia (38%) and immunodeficiency (38%). The total levels of Igs (IgE, IgA, and IgM) were positively correlated with both white blood cell count and absolute lymphocyte count. CONCLUSION: Serum Ig expression Pattern in patients diagnosed with T. marneffei infection might serve as an effective prognostic marker which would help with the development of early interventions for children with this fatal disease.

Collecting Duct Carcinoma of the Kidney: A Single-Center Retrospective Study of 23 Cases.

Objective: To explore the clinical, imaging, pathologic features, treatment, and prognostic outcomes in 23 cases of collecting duct carcinoma (CDC) from a single center. Methods: The clinical and imaging findings, pathological features, treatment methods, and outcomes of the 23 patients with CDC confirmed by microscopic examination between 2003 and 2020 at our institution were retrospectively reviewed. Descriptive statistics of demographic and clinical variables were applied. Kaplan-Meier method was used to analyze survival data and log-rank test statistic survival differences between groups. Cox regression analysis was employed to identify variables independently related to overall survival (OS). Results: A total of 23 patients with CDC were identified. The mean age was 50.8 years. Stage III or IV tumors were diagnosed in 82.6% of the patients at diagnosis. The average size of the tumor was 6.58 cm, and the left kidney was more involved than the right. The median OS was 12 months. The OS rates at 1 and 2 years were 43.5% and 26.1%, respectively. Twenty patients underwent nephrectomy, 3 underwent nephroureterectomy, and 9 (39.1%) patients received subsequent therapeutic interventions following surgery. Distant metastasis and no symptoms at initial diagnosis proved to be an independent factor of unfavorable survival in Cox regression analysis. Conclusions: CDC is a rare and highly aggressive malignant renal tumor, and most patients present at an advanced stage at initial diagnosis. More than half of the patients died within 1 year after surgery. Distant metastasis and no clinical symptoms at initial diagnosis were independent risk prognostic factors for patients with CDC.

Exosomal AP000439.2 from clear cell renal cell carcinoma induces M2 macrophage polarization to promote tumor progression through activation of STAT3.

BACKGROUND: Tumorigenic phenotype of M2 tumor-associated macrophages promote tumor progression in response to exosomes cues imposed by tumor cells. However, the effect and underlying mechanisms of clear cell renal cell carcinoma (ccRCC)-derived exosomes (ccRCC-exo) on instructing macrophages phenotype remains unclear. METHODS: Macrophages were cocultured with ccRCC-exo and then evaluate the polarization of macrophages and migration of ccRCC cells. The effect and mechanism of lncRNA AP000439.2 overexpressed or deleted exosomes on macrophages M2 polarization were examined. Xenograft tumor mice model was used for in vivo validation. RESULTS: The ccRCC-exo significantly activated macrophages to M2 phenotype presented by increased expression of transforming growth factor-beta (TGF-ß) and interleukin 10 (IL-10) at mRNA and protein levels, and these M2 macrophages in turn facilitating the migration of ccRCC cells. LncRNA AP000439.2 was highly enriched in the ccRCC-exo. Overexpression of exosomal AP000439.2 promoted M2 macrophage polarization whereas AP000439.2-deficient exosome had the opposite effects. Nuclear-localized AP000439.2 directly interacted with signal transducer and activator of transcription 3 (STAT3) proteins and phosphorylated STAT3 in macrophages. RNA-Seq results showed overexpression of AP000439.2 activated NF-κB signaling pathway. Silencing of STAT3 suppressed overexpression of AP000439.2-induced up-regulation of TGF-ß and IL-10 expression, and p65 phosphorylation. AP000439.2-deleted exosome inhibited tumor growth in vivo. CONCLUSION: Exosomes from ccRCC deliver AP000439.2 to promote M2 macrophage polarization via STAT3, thus enhancing ccRCC progression, indicating exosomal AP000439.2 might be a novel therapeutic target in ccRCC. Video Abstract.

KCNN4 may weaken anti-tumor immune response via raising Tregs and diminishing resting mast cells in clear cell renal cell carcinoma.

BACKGROUND: Studies over the past decade have shown that competitive endogenous RNA (ceRNA) plays an essential role in the tumorigenesis and progression of clear cell renal cell carcinoma (ccRCC). Meanwhile, immune checkpoint blocker is gradually moving towards the first-line treatment of ccRCC. Hence, it's urgent to develop a new prediction model for the efficiency of immunotherapy. At present, there is no study to reveal the effect of ceRNA network on the efficiency of immunotherapy for ccRCC. METHODS: To systematically analyze the effect of ceRNA hub genes in ccRCCon immune response, we constructed prognosis models based on ceRNAs and immune cells, respectively. We constructed ceRNA network using hypergeometric distribution test and correlation analysis with R script based on The Cancer Genome Atlas (TCGA) database. We then applied the Cibersort algorithm to simulate the infiltration overview of immune cells in kidney renal clear carcinoma (KIRC) samples. Prognosis-related immune cells were screened and a predictive model of these cells was constructed. Prognosis-related immune cells and ceRNA hub genes were performed with co-expression analysis. Finally, qRT-PCR and immunofluorescence assays were performed to validate the results. RESULTS: The construction of ceRNA related prognosis model contained 8 hub genes, including RELT, MYO9B, KCNN4, SIX1, OTOGL, MALAT1, hsa-miR-130b-3p, and hsa-miR-21-5p. The area under the receiver operating characteristic curve (AUC) was 0.77 at 5 years. For the construction of immune cells prognosis model, 3 immune cells (T cells regulatory, Macrophages, Mast cells resting) were adopted, and the AUC was 0.65 at 5 years. We then merged the two models by correlation analysis and co-expression analysis. Finally, we found that KCNN4 positively correlates with T cells regulatory (Tregs) and negatively correlates with mast cells resting significantly. Furthermore, higher expression of KCNN4 may lead to a higher potential for immune evasion and lower efficiency for immune checkpoint inhibitors (ICIs). CONCLUSIONS: Generally, this is the first study to assess the prognostic value of immune related ceRNA hub genes in ccRCC, and KCNN4 was finally demonstrated to be a key regulatory factor with strong correlation with Tregs and mast cells resting.

[Long-term effect of finasteride on high-risk patients with benign prostatic hyperplasia after implantation of thermo-expandable spiral prostatic stent].

OBJECTIVE: To investigate the long-term effect of finasteride (FS) on high-risk BPH patients after treated by implantation of thermo-expandable spiral prostatic stent (TESPS). METHODS: We retrospectively analyzed the clinical data on 63 cases of BPH treated by implantation of TESPS in our Department of Urology from January 2017 to January 2019. All the patients received oral FS after operation except two cases of stent removal because of infection, 37 for more than 12 months (the long-term FS group) and the other 24 for less than 12 months (the control group). We followed up the patients at 3, 6, 12, 24, 36 and 48 months postoperatively, recorded the incidence of hematuria and infection, IPSS, maximum urinary flow rate (Qmax) and residual urine volume (PVR), and compared them between the two groups of patients. RESULTS: At 48 months after operation, the incidence rates of postoperative hematuria and infection were significantly lower in the long-term FS group than in the control (P < 0.05), but evidently increasing with the prolonging of medication time. The total effectiveness rate was as high as 95.1% at 3 months, but only 63.6% at 48 months, significantly higher, however, in the long-term FS than in the control group (69.2% vs 55.6%, P < 0.05), and the IPSS, Qmax and PVR were also remarkably higher in the former than in the latter group (P < 0.05). CONCLUSION: The long-term effect of TESPS implantation is definite in the treatment of BPH-induced dysuria, and it can be used as a first-choice method for the patients at high risk and unsuitable for surgery. Finasteride has an evident advantage in preventing hematuria and infection after prostatic stent implantation, and long-term medication of finasteride improves long-term outcomes.

QPCT regulation by CTCF leads to sunitinib resistance in renal cell carcinoma by promoting angiogenesis.

Sunitinib is widely used as a first­line treatment for advanced renal cell carcinoma (RCC). However, a number of patients with RCC who receive sunitinib develop drug resistance; and the biological mechanisms involved in resistance to sunitinib remain unclear. It has previously been suggested that the protein glutaminyl­peptide cyclotransferase (QPCT) is closely related to sunitinib resistance in RCC. Thus, in the present study, in order to further examine the molecular mechanisms responsible for sunitinib resistance in RCC, sunitinib­non­responsive and ­responsive RCC tissue and plasma samples were collected and additional experiments were performed in order to elucidate the molecular mechanisms responsible for sunitinib resistance in RCC. The upstream and downstream regulatory mechanisms of QPCT were also evaluated. On the whole, the data from the present study suggest that QPCT, CCCTC­binding factor (CTCF) and phosphatidylinositol­4,5­bisphosphate 3­kinase catalytic subunit alpha (PIK3CA) may be used as targets for predicting, reversing and treating sunitinib­resistant RCC.

Two-Stage Water Jet Landing Point Prediction Model for Intelligent Water Shooting Robot.

In this paper, an intelligent water shooting robot system for situations of carrier shake and target movement is designed, which uses a 2 DOF (degree of freedom) robot as an actuator, a photoelectric camera to detect and track the desired target, and a gyroscope to keep the robot's body stable when it is mounted on the motion carriers. Particularly, for the accurate shooting of the designed system, an online tuning model of the water jet landing point based on the back-propagation algorithm was proposed. The model has two stages. In the first stage, the polyfit function of Matlab is used to fit a model that satisfies the law of jet motion in ideal conditions without interference. In the second stage, the model uses the back-propagation algorithm to update the parameters online according to the visual feedback of the landing point position. The model established by this method can dynamically eliminate the interference of external factors and realize precise on-target shooting. The simulation results show that the model can dynamically adjust the parameters according to the state relationship between the landing point and the desired target, which keeps the predicted pitch angle error within 0.1°. In the test on the actual platform, when the landing point is 0.5 m away from the position of the desired target, the model only needs 0.3 s to adjust the water jet to hit the target. Compared to the state-of-the-art method, GA-BP (genetic algorithm-back-propagation), the proposed method's predicted pitch angle error is within 0.1 degree with 1/4 model parameters, while costing 1/7 forward propagation time and 1/200 back-propagation calculation time.

Evaluation of three microhaplotypes in individual identification and ancestry inference.

Microhaplotype as an emerging genetic marker has attracted more attention in forensic field. The purpose of this study was to evaluate the potential of microhaplotypes in individual identification and ancestry inference in Chinese Hainan Li and 26 1000 G populations. Three microhaplotypes were genotyped from 100 Li individuals using Agena MassARRAY. Moreover, 2504 individuals from 26 populations (1000 Genomes Project database) were enrolled. The genotypes frequencies of microhaplotypes in each population were calculated by the Plink software. We used Structure, Arlequin, and MEGA6 software to analyze the genetic structure, differentiation and genetic background difference, respectively. The forensic parameters of these microhaplotypes were calculated using Modified Powerstats software. The distribution of genotypes frequencies of three microhaplotypes elaborated the high diversities among the Li and 26 1000 G populations. Li population had a close genetic relationship with EAS populations using structure analysis. No differentiation was observed between Li and CHS population by Fst analysis. The NJ tree showed that the genetic background of Li and CHS is most similar. The average heterozygosity (HE), probability of match (PM), power of discrimination (PD), probability of exclusion (PE) and polymorphism information content (PIC) values for the three microhaplotypes in 27 populations were 0.535, 0.497, 0.465, 0.325, and 0.481, respectively. In conclusion, our results revealed three microhaplotypes as individual identification and ancestry inference genetic markers among Li population and 26 1000 G populations. Future studies are needed to confirm our results with larger samples and select much higher forensic efficacy microhaplotypes.

Genome-wide CRISPR-Cas9 screen identified KLF11 as a druggable suppressor for sarcoma cancer stem cells.

Cancer stem cells (CSCs) are involved in tumorigenesis, recurrence, and therapy resistance. To identify critical regulators of sarcoma CSCs, we performed a reporter-based genome-wide CRISPR-Cas9 screen and uncovered Kruppel-like factor 11 (KLF11) as top candidate. In vitro and in vivo functional annotation defined a negative role of KLF11 in CSCs. Mechanistically, KLF11 and YAP/TEAD bound to adjacent DNA sites along with direct interaction. KLF11 recruited SIN3A/HDAC to suppress the transcriptional output of YAP/TEAD, which, in turn, promoted KLF11 transcription, forming a negative feedback loop. However, in CSCs, this negative feedback was lost because of epigenetic silence of KLF11, causing sustained YAP activation. Low KLF11 was associated with poor prognosis and chemotherapy response in patients with sarcoma. Pharmacological activation of KLF11 by thiazolidinedione effectively restored chemotherapy response. Collectively, our study identifies KLF11 as a negative regulator in sarcoma CSCs and potential therapeutic target.

Identification of Immune-Related Cells and Genes in Tumor Microenvironment of Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is one of the most common tumors in the urinary system. Progression in immunotherapy has provided novel options for the ccRCC treatment. However, the understanding of the ccRCC microenvironment and the potential therapeutic targets in the microenvironment is still unclear. Here, we analyzed the gene expression profile of ccRCC tumors from the Cancer Genome Atlas (TCGA) and calculated the abundance ratios of immune cells for each sample. Then, seven types of immune cells were found to be correlated to overall survival, and 3863 immune-related genes were identified by analyzing differentially expressed genes. We also found that the function of immune-related genes was mainly focused on ligand-receptor binding and signaling pathway transductions. Additionally, we identified 13 hub genes by analyzing the protein-protein interaction network, and seven of them are related to overall survival. Our study not only expands the understanding of fundamental biological features of microenvironment but also provides potential therapeutic targets.

Knockdown of CDCA8 inhibits the proliferation and enhances the apoptosis of bladder cancer cells.

Bladder cancer is a tumour of the urinary system with high mortality, and there is also a great lack of therapeutic targets in the clinic. Cell division cycle associated 8 (CDCA8), an important component of the vertebrate chromosomal passenger complex, is highly expressed in various tumours and promotes tumour development. However, the role of CDCA8 in bladder cancer is not fully understood. This study aimed to reveal the function of CDCA8 in bladder cancer by determining the relationship between CDCA8 expression and proliferation, metastasis and apoptosis of bladder cancer cells. Firstly, we studied the mRNA expression of CDCA8 through the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases and analysed the correlation between CDCA8 expression and prognosis of patients with bladder cancer. We also verified CDCA8 expression in bladder cancer tissues by immunohistochemistry. In addition, CDCA8 expression was inhibited in bladder cancer T24 and 5637 cells, and the effects of CDCA8 on the proliferation, migration and invasion of bladder cancer cell lines were investigated using cell counting kit-8, colony formation, cell cycle, apoptosis, wound healing and Transwell invasion assays. Results showed that CDCA8 was highly expressed in bladder cancer compared with normal tissues, and the high CDCA8 expression was significantly correlated with the poor prognosis of patients. Inhibiting CDCA8 expression inhibited the proliferation, migration and invasion of T24 and 5637 cells and induced the apoptosis of bladder cancer cells. CDCA8 was involved in the regulation of the growth cycle of bladder cancer cells. Bioinformatics-based mechanism analysis revealed that high CDCA8 expression may affect the cell cycle and P53 signalling pathways. In conclusion, our results suggest that CDCA8 is highly expressed in bladder cancer and can promote tumour development. Hence, CDCA8 may serve as an effective therapeutic target for treatment of bladder cancer.

Oncogenic roles of the cholesterol metabolite 25-hydroxycholesterol in bladder cancer.

Oxysterols, such as 24S-hydroxycholesterol and 25-hydroxycholesterol are oxidation products of cholesterol generated by enzymatic reactions. The pathological effects of oxysterols have been described in multiple types of cancer, including cancers of the skin, lung, colon, breast and bile ducts. The molecular mechanisms underlying oxysterol-induced cancer initiation and progression have yet to be completely elucidated, and to the best of our knowledge, no prior data on the role of 24S-hydroxycholesterol and 25-hydroxycholesterol in bladder cancer exists. The results of the present study demonstrated that 25-hydroxycholesterol is increased in bladder cancer tissues, and that it promotes proliferation and the epithelial-to-mesenchymal transition in human T24 and RT4 bladder cancer cells. It was also observed that 25-hydroxycholesterol promotes Adriamycin resistance in T24 and RT4 cells, and that high levels of 25-hydroxycholesterol in bladder cancer are associated with a poor outcome. Therefore, 25-hydroxycholesterol, a primary metabolite of cholesterol, may serve an important role in the progression of bladder cancer.

Preparation and performance of a BTDA-modified polyurea microcapsule for encapsulating avermectin.

A pesticide microcapsule was prepared by encapsulating avermectin (AVM) in a polyurea microcapsule via interfacial polymerization in acetic ether/water emulsion. The polyurea microcapsule was consisted of chitosan oligomer (CO) as the membrane material and diphenyl methane-4,4'-diisocyanate (MDI) as the crosslinker. A chemical modification was carried out by grafting a UV-absorbent, 3,3',4,4'-benzophenonetetracarboxylic dianhydride (BTDA), to CO before interfacial polymerization to enhance the UV-resistance of the microcapsule. The BTDA grafted CO (CO-BTDA) and the AVM microcapsules were characterized by a variety of instrumental techniques, including NMR, FTIR, UV-vis, GPC-LS, DLS, SEM and TEM. The in vitro release test showed that the polyurea microcapsule maintained the sustained release of AVM for a longer period (up to 120 h) in comparison with the commercial AVM formulations (within 24 h). The photodegradation test revealed that the polyurea microcapsule significantly reduced the AVM degradation and extended the half-life of AVM from 4.16 h to 9.43 h. The AVM degradation was further reduced by using the BTDA-modified polyurea microcapsule. The corresponding half-life was extended up to 17.33 h and can be mediated by changing the mass ratio of BTDA: CO during the synthesis of CO-BTDA. The use of polyurea microcapsule did not raise a concern about pesticide residue as no AVM was detected after the photodegradation test. In addition, the polyurea microcapsule itself was subject to degradation under sunlight exposure, which reduced its residue in the environment.

Cancer-associated methylated lncRNAs in patients with bladder cancer.

Epigenetic modifications via DNA methylation and long non-coding RNAs (lncRNAs) have been identified in bladder cancer (BC). However, DNA methylation of lncRNAs involved in BC has not been elucidated. Here, DNA immunoprecipitation-sequencing (MeDIP-seq) and RNA-sequencing (RNA-seq) were carried out using eight paired tumor and adjacent normal tissue samples from patients with BC. Differences in methylation patterns between tumors and controls were compared and the percentage of differentially methylated genes, including lncRNA genes, was calculated. RNA-seq data were subjected to gene ontology (GO), Kyoto encyclopedia of genes, and genomes (KEGG) analysis. The association between DNA methylation modification and lncRNA expression was determined by pairwise analysis of MeDIP-seq and RNA-seq data. The most enriched motifs in the promoter region, as well as the methylated density in the 3 kb region surrounding super-enhancers of lncRNA genes, were analyzed. A peak of 5mC methylation in the region 2 kb upstream of the transcription start site (TSS), with the lowest point in the TSS region, was observed. In total, 436 and 239 genes were identified to be hyper and hypomethylated, respectively, in BC tissue around the TSS region. RNA-seq revealed differentially expressed lncRNAs between tumor and normal tissues, many of which were cancer-associated lncRNAs based on GO and KEGG pathway analysis. Combined MeDIP-seq and RNA-seq analysis revealed that expression of 26 lncRNAs were candidates of 5mC controlled genes. The possible link between 5mC modification and differential lncRNAs may relate to enrichment of 5mC reads in the region surrounding super-enhancers of lncRNA. Survival analysis indicated that the methylated lncRNA, LINC00574, was associated with shorter overall survival time in patients with BC (HR = 1.7, p-value = 0.035). Taken together, these findings indicate that lncRNAs genes are under control of DNA methylation. Methylated lncRNA genes, which are transcripted to LINC00574, may serve as biomarkers for BC prognosis.

High temperature singlet-based magnetism from Hund's rule correlations.

Uranium compounds can manifest a wide range of fascinating many-body phenomena, and are often thought to be poised at a crossover between localized and itinerant regimes for 5f electrons. The antiferromagnetic dipnictide USb2 has been of recent interest due to the discovery of rich proximate phase diagrams and unusual quantum coherence phenomena. Here, linear-dichroic X-ray absorption and elastic neutron scattering are used to characterize electronic symmetries on uranium in USb2 and isostructural UBi2. Of these two materials, only USb2 is found to enable strong Hund's rule alignment of local magnetic degrees of freedom, and to undergo distinctive changes in local atomic multiplet symmetry across the magnetic phase transition. Theoretical analysis reveals that these and other anomalous properties of the material may be understood by attributing it as the first known high temperature realization of a singlet ground state magnet, in which magnetism occurs through a process that resembles exciton condensation.