Soil ecoenzyme activities coupled with soil properties and plant biomass strongly influence the variation in soil organic carbon components in semi-arid degraded wetlands.

Wetland degradation can induce alterations in plant biomass, soil properties, and soil ecoenzyme activities, consequently influencing soil organic carbon components. Despite extensive investigations into the relationships among plant characteristics, soil properties, and soil organic carbon components, the enzymatic mechanisms underlying changes in soil organic carbon components, particularly the impact and contribution of ecoenzyme activities, remain poorly understood. This study compared the soil organic carbon components at a depth of 0-20 cm in wetlands in the semi-arid western Songnen Plain under different degradation levels and explored plant biomass, soil properties, and soil ecoenzyme activities. The results showed that the soil total organic carbon, labile organic carbon, and recalcitrant organic carbon contents in the degraded wetlands were generally lower than those in the non-degraded wetlands. Furthermore, the soil nutrient contents and soil ß-1,4-glucosidase, L-leucine aminopeptidase, and acid phosphatase activities were also lower in the degraded wetlands than in the non-degraded wetlands. Vector analysis of enzymatic stoichiometry revealed that wetland degradation did not increase microbial carbon limitation. The soil organic carbon components showed significant positive correlations with plant biomass, soil water content, soil total nitrogen, soil total phosphorus, as well as soil ecoenzyme activities. Variation partitioning analysis revealed that plant biomass, soil properties, soil ecoenzyme activities collectively accounted for 78.5 % variation in soil organic carbon components, among which plant biomass, soil properties, soil ecoenzyme activities, and their interactions explaining 4.2 %, 8.0 %, 7.9 %, and 24.5 % of the variation, respectively. Therefore, the impact of soil ecoenzyme activities and soil properties on soil organic carbon component changes was greater than that of plant biomass, with the interaction of these three factors playing a crucial role in soil organic carbon formation. This study provides a theoretical basis for scientifically evaluating the carbon sink function of degraded wetland soil and preserving the wetland soil carbon pool.

Herbivory and elevated levels of CO2 and nutrients separately, rather than synergistically, impacted biomass production and allocation in invasive and native plant species.

Large parts of the Earth are experiencing environmental change caused by alien plant invasions, rising atmospheric concentration of carbon dioxide (CO2 ), and nutrient enrichments. Elevated CO2 and nutrient concentrations can separately favour growth of invasive plants over that of natives but how herbivory may modulate the magnitude and direction of net responses by the two groups of plants to simultaneous CO2 and nutrient enrichments remains unknown. In line with the enemy release hypothesis, invasive plant species should reallocate metabolites from costly anti-herbivore defences into greater growth following escape from intense herbivory in the native range. Therefore, invasive plants should have greater growth than native plants under simultaneous CO2 and nutrient enrichments in the absence of herbivory. To test this prediction, we grew nine congeneric pairs of invasive and native plant species that naturally co-occurred in grasslands in China under two levels each of nutrient enrichment (low-nutrient vs. high-nutrient), herbivory (with herbivory vs. without herbivory) and under ambient (412.9 ± 0.6 ppm) and elevated (790.1 ± 6.2 ppm) levels of CO2 concentrations in open top chambers in a common garden. Elevated CO2 and nutrient enrichment separately increased total plant biomass, while herbivory reduced it regardless of the plant invasive status. High-nutrient treatment caused the plants to allocate a significantly lower proportion of total biomass to roots, while herbivory induced an opposite pattern. Herbivory suppressed total biomass production more strongly in native plants than invasive plants. The plants exhibited significant interspecific and intergeneric variation in their responses to the various treatment combinations. Overall, these results suggest that elevated CO2 and nutrients and herbivory may separately, rather than synergistically, impact productivity of the invasive and co-occurring native plant species in our study system. Moreover, interspecific variation in resource-use strategies was more important than invasive status in determining plant responses to the various treatment combinations.

Corrigendum: Long non-coding RNA CCAT1 acts as an oncogene and promotes sunitinib resistance in renal cell carcinoma.

[This corrects the article DOI: 10.3389/fonc.2020.516552.].

Associations between grain intake and hospitalized nephrolithiasis in Chinese adults: a case-control study.

Introduction: nephrolithiasis is one of the most common urological disorders. Grains are essential staple foods worldwide. This study aimed to investigate the associations between whole grains and refined grains intake, and hospitalized nephrolithiasis in a Chinese population. Methods: the patients and healthy participants were enrolled in the Shenyang sub-cohort of Tianjin Chronic Low-Grade Systemic Inflammation and Health Cohort Study. After selecting and matching by age (±one year) and sex using a 1 : 2 ratio, a total of 666 participants (222 patients and 444 healthy controls) were included. Whole grains and refined grains intake was measured using a validated self-administered food frequency questionnaire. Multivariate conditional logistic regression analysis was used to evaluate the associations between whole grains and refined grains intake with hospitalized nephrolithiasis. Results: after multivariable adjustments, a higher intake of whole grains was inversely associated with hospitalized nephrolithiasis. Compared to participants with the lowest tertile of whole grains intake, the adjusted odds ratio (OR) and 95% confidence interval (CI) of hospitalized nephrolithiasis for participants in the highest tertile was 0.58 (0.26, 0.81) (P for trend = 0.020). In contrast, a higher intake of refined grains was positively associated with nephrolithiasis. Compared to participants with the lowest tertile of refined grains intake, the adjusted OR (95% CI) of hospitalized nephrolithiasis for participants in the highest tertile was 3.75 (1.48, 9.52) (P for trend = 0.006). The results were consistent in both genders. Conclusion: the consumption of whole grains was found to be negatively associated with hospitalized nephrolithiasis, while the consumption of refined grains was positively associated with hospitalized nephrolithiasis. Therefore, a substitution of whole grains for refined grains consumption may assist in hospitalized nephrolithiasis prevention.

Prospective comparison of extracorporeal shock wave lithotripsy versus flexible ureterorenoscopy in patients with non-lower pole kidney stones under the COVID-19 pandemic.

Both shock wave lithotripsy (SWL) and flexible ureterorenoscopy (F-URS) are recommended as the first choice for non-lower pole kidney stones. Therefore, we conducted a prospective study to evaluate the efficacy, safety, and cost of SWL versus F-URS in patients with solitary non-lower pole kidney stones ≤ 20 mm under the COVID-19 pandemic. This prospective study was conducted in a tertiary hospital from June 2020 to April 2022. Patients who underwent lithotripsy (SWL or F-URS) for non-lower pole kidney stones were enrolled in this study. The stone-free rate (SFR), retreatment rate, complications, and cost were recorded. Propensity score-matched (PSM) analysis was performed. A total of 699 patients were finally included, of which 81.3% (568) were treated with SWL and 18.7% (131) underwent F-URS. After PSM, SWL showed equivalent SFR (87.9% vs. 91.1%, P = 0.323), retreatment rate (8.6% vs. 4.8%, P = 0.169), and adjunctive procedure (2.6% vs. 4.9%, P = 0.385) compared with F-URS. Complications were scarce and also comparable between SWL and F-URS (6.0% vs 7.7%, P > 0.05), while the incidence of ureteral perforation was higher in the F-URS group compared with the SWL group (1.5% vs 0%, P = 0.008). The hospital stay was significantly shorter (1 day vs 2 days, P < 0.001), and the cost was considerably less (1200 vs 30,083, P < 0.001) in the SWL group compared with the F-URS group. This prospective cohort demonstrated that SWL had equivalent efficacy with more safety and cost benefits than F-URS in treating patients with solitary non-lower pole kidney stones ≤ 20 mm. During the COVID-19 pandemic, SWL may have benefits in preserving hospital resources and limiting opportunity for virus transmission, compared to URS. These findings may guide clinical practice.

Nutrient enrichment promotes invasion success of alien plants via increased growth and suppression of chemical defenses.

In support of the prediction of the enemy release hypothesis regarding a growth-defense trade-off, invasive alien plants often exhibit greater growth and lower anti-herbivory defenses than native plants. However, it remains unclear how nutrient enrichment of invaded habitats may influence competitive interactions between invasive alien and co-occurring native plants, as well as production of anti-herbivore defense compounds, growth-promoting hormones, and defense-regulating hormones by the two groups of plants. Here, we tested whether: (i) nutrient enrichment causes invasive alien plants to produce greater biomass and lower concentrations of the defense compounds flavonoids and tannins than native plants; and (ii) invasive alien plants produce lower concentrations of a defense-regulating hormone jasmonic acid (JA) and higher concentrations of a growth-promoting hormone gibberellic acid (GA3). In a greenhouse experiment, we grew five congeneric pairs of invasive alien and native plant species under two levels each of nutrient enrichment (low vs. high), simulated herbivory (leaf clipping vs. no-clipping), and competition (alone vs. competition) in 2.5-L pots. In the absence of competition, high-nutrient treatment induced a greater increase in total biomass of invasive alien species than that of native species, whereas the reverse was true under competition as native species benefitted more from nutrient enrichment than invasive alien species. Moreover, high-nutrient treatment caused a greater increase in total biomass of invasive alien species than that of native species in the presence of simulated herbivory. Competition induced higher production of flavonoids and tannins. Simulated herbivory induced higher flavonoid expression in invasive alien plants under low-nutrient than high-nutrient treatments. However, flavonoid concentrations of native plants did not change under nutrient enrichment and simulated herbivory treatments. Invasive alien plants produced higher concentrations of GA3 than native plants. Taken together, these results suggest that impact of nutrient enrichment on growth of invasive alien and co-occurring native plants may depend on the level of competition that they experience. Moreover, invasive alien plants might adjust their flavonoid-based defense more efficiently than native plants in response to variation in soil nutrient availability and herbivory pressure. Our findings suggest that large-scale efforts to reduce nutrient enrichment of invaded habitats may help to control future invasiveness of target alien plant species.

Prospective Comparison of Local Anesthesia with General or Spinal Anesthesia in Patients Treated with Microscopic Varicocelectomy.

It is unclear whether local anesthesia (LA) is a viable and safe alternative to general anesthesia (GA) or spinal anesthesia (SA) for microscopic varicocelectomy. As a result, we designed a prospective trial to compare the pain relief, complications, and cost of LA with GA or SA in subinguinal microscopic varicocelectomy (MSV), using the propensity score matching method (PSM). This prospective study was conducted in a tertiary hospital from February 2021 to April 2022. Patients who underwent subinguinal MSV for varicocele were enrolled. The perioperative visual analog scale (VAS) scores, anesthesia-associated side effects, and cost data were recorded, and PSM analysis was performed. Finally, 354 patients were included, of whom 61.0% (216) were treated with LA, and 39.0% (138) underwent GA or LA. After PSM, the patients in the LA group exhibited lower VAS scores both three hours and one day after surgery, and a lower incidence of postoperative analgesic requirement; a lower ratio of patients who experienced anesthesia-associated side effects was also observed in the LA group, compared with the GA or SA group (all p < 0.001). The rate of perioperative satisfaction for patients was higher, the hospital stays and days to return to normal activity were shorter, and the cost was less in the LA group than in the patients in the GA or SA group (all p < 0.001). This prospective PSM cohort demonstrated that LA has the advantages of perioperative pain relief, reduced anesthesia-associated side effects, and cost, compared with GA or SA. It indicated that LA is an effective and safe technique for subinguinal MSV, and may guide clinical practice.

Nomogram for predicting spontaneous pregnancy after microscopic varicocelectomy in infertile men with normal hormone.

INTRODUCTION: The current challenge for the treatment of varicocele is identifying patients who could benefit the most from surgery. We aimed to develop and validate a nomogram for predicting spontaneous pregnancy following microscopic varicocelectomy in infertile men, based on a large cohort. METHODS: Two hundred eighty-two consecutive patients who underwent microscopic varicocelectomy from January 2018 to December 2020 were enrolled as participants in the study. Xiang Hua center (206 patients) as a development cohort. Hu Nan center (76 patients) as a validation cohort. Patient clinicopathologic data were recorded. Multivariate logistic regression was used to build a predictive model with regression coefficients. Then, backward stepwise selection was applied, and the likelihood ratio test with Akaike's information criterion was used as the stopping rule. The performance of this predictive model was assessed for discrimination, calibration, and clinical usefulness. RESULTS: Predictors of this model included the age of female partners, diameter of veins, initial and increased total progressively motile sperm count. The model demonstrated good discrimination with an AUROC of 0.925 (p < 0.001) and calibration (Unreliability test, p = 0.522) in the validation cohort. Furthermore, the model was clinically useful, according to decision curve analysis. CONCLUSIONS: Our findings indicated that younger female partners, larger diameter of veins, higher initial and increased total progressively motile sperm count were significant predictors of spontaneous pregnancy in infertile men, post microscopic varicocelectomy. This nomogram may assist in individual decision-making on the treatment strategy of varicocele preoperatively and improve the treatment outcome.

Inhibition of PP2A by LB100 sensitizes bladder cancer cells to chemotherapy by inducing p21 degradation.

PURPOSE: Bladder carcinoma (BLCA) is the most common urinary tract malignancy and exhibits a poor response to chemotherapy. Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase involved in a wide variety of regulatory cellular processes, including apoptosis and the DNA-damage response (DDR). LB100, a small molecule inhibitor of PP2A, has been shown to act as a chemo-sensitizer in multiple types of cancer. However, the anti-tumor effect and mode of action of LB100 in BLCA have yet to be identified. METHODS: In vitro and in vivo experiments were performed to assess the anti-tumor effect of LB100 alone or in combination with gemcitabine. Mass spectrometry (MS)-based phosphoproteomics analysis was used to identify the downstream substrates of PP2A and to explore the mechanism underlying LB100-induced DNA damage and apoptosis. In addition, we established a chemo-resistant BLCA cell line (RT-112-R) by prolonged drug exposure and determined the effect of LB100 in enhancing genotoxicity in BLCA cell lines and xenograft mouse models. RESULTS: We found that LB100 is sufficient to induce an anti-tumor response in BLCA cells by inducing DNA damage and apoptosis both in vitro and in vivo. Furthermore, we found that PP2A potentially dephosphorylates p-p21-ser130 to stabilize p21. Inhibition of PP2A by LB100 increased the level of p-p21-ser130, subsequently leading to a reduction in p21 level in a dose-dependent manner. In addition, we found that treatment of LB100 abrogated the G1/S cell cycle checkpoint, resulting in increased phosphorylation of γH2AX in BLCA cells. Moreover, LB100 enhanced genotoxicity in chemo-resistant BLCA cells by inducing DNA damage and apoptosis in vitro and in vivo. CONCLUSION: Our findings indicate that PP2A may serve as a potential therapeutic target in BLCA through regulating p21 stability.

The prevalence and risk factors for major depression and suicidal ideation in medical residents based on a large multi-center cross-sectional study using the propensity score-matched method.

INTRODUCTION: We determined the prevalence of major depression and suicidal ideation, and the associated risk factors in a large sample of Chinese resident physicians. METHODS: This multi-center cross-sectional study was conducted from December 2019 to February 2020 and involved 1343 residents from eight centers. Extensive characteristics, including demographics, dietary habits, life-related factors, work-related factors, and psychological factors were collected based on a self-reported questionnaire. Specific scales measured the levels of sleep quality, physical activity, depression, perceived organization support, psychological capital, and burnout. Adjusted odds ratios and 95% confidence intervals were determined by binary paired logistic regression. RESULTS: Of the residents enrolled in the study, 12.90% suffered from major depression and 9.70% suffered from suicidal ideation. Four overlapped independent risk factors were identified for major depression and suicidal ideation: poor sleep quality (OR = 1.317, OR = 1.200); lower optimism of psychological capital (OR = 0.899, OR = 0.835); higher depersonalization, (OR = 1.086, OR = 1.097); and reduced personal accomplishment (OR = 0.963, OR = 0.962). The inappropriate working duration weekly (< 40 h vs. 40-60 h; OR = 2.812, > 60 h vs. 40-60 h; OR = 1.945), and higher emotional exhaustion (OR = 1.121) were the only risk factors for major depression. Higher hope of psychological capital (OR = 1.077) was only for suicidal ideation. CONCLUSION: This study revealed a substantial prevalence of major depression and suicidal ideation in Chinese residents, and identified several shared risk factors for major depression and suicidal ideation. These findings enrich the existing theoretical model of depression and demonstrated a critical need for additional studies that investigate intervention strategies that can address the mental health in residents. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900027707. Registered 24 Nov. 2019, http://www.chictr.org.cn/index.aspx.

NCAPH promotes cell proliferation and inhibits cell apoptosis of bladder cancer cells through MEK/ERK signaling pathway.

Bladder cancer (BC) is one of the most common cancers world-wide with a poor prognosis. Non-SMC (Structural Maintenance of Chromosomes)-condensin I complex subunit H (NCAPH) is a regulatory subunit of the condensin I complex and plays an important role in tumorigenesis and progression in several types of cancers. However, the role of NCAPH in BC remains unknown. In this study, we tried to reveal the biological functions of NCAPH in BC. We detected the expressions of NCAPH in BC and adjacent tissues, and BC cells lines. Subsequently, the gain- and loss-of-function experiments were performed to determine the effects of NCAPH on BC cell proliferation, apoptosis, and activation of the MEK/ERK signaling pathway in vitro. Moreover, we used BALB/c nude mice and established a xenograft model to investigate whether silence NCAPH using shRNA targeting NCAPH (shNCAPH) can inhibit BC tumor growth in vivo. The results showed NCAPH was overexpressed in BC tissues compared to adjacent tissues and highly expressed in BC cell lines. Additionally, overexpression of NCAPH promoted cell proliferation and inhibited apoptosis in SW780 cells. Conversely, knockdown of NCAPH reduced cell proliferation and enhanced apoptosis in UMUC3 cells. Furthermore, we found that the NCAPH activated the MEK/ERK signaling pathway in BC cells. MEK1/2 inhibitor U0126 blocked the increase of cell proliferation regulated by NCAPH overexpression. Knockdown of NCAPH significantly inhibited tumor growth in mice. Our results suggest that NCAPH might play an important role in BC progression and provide the potential marker in the diagnosis of BC.

Identification of subgroups along the glycolysis-cholesterol synthesis axis and the development of an associated prognostic risk model.

BACKGROUND: Skin cutaneous melanoma (SKCM) is one of the most highly prevalent and complicated malignancies. Glycolysis and cholesterogenesis pathways both play important roles in cancer metabolic adaptations. The main aims of this study are to subtype SKCM based on glycolytic and cholesterogenic genes and to build a clinical outcome predictive algorithm based on the subtypes. METHODS: A dataset with 471 SKCM specimens was downloaded from The Cancer Genome Atlas (TCGA) database. We extracted and clustered genes from the Molecular Signatures Database v7.2 and acquired co-expressed glycolytic and cholesterogenic genes. We then subtyped the SKCM samples and validated the efficacy of subtypes with respect to simple nucleotide variations (SNVs), copy number variation (CNV), patients' survival statuses, tumor microenvironment, and proliferation scores. We also constructed a risk score model based on metabolic subclassification and verified the model using validating datasets. Finally, we explored potential drugs for high-risk SKCM patients. RESULTS: SKCM patients were divided into four subtype groups: glycolytic, cholesterogenic, mixed, and quiescent subgroups. The glycolytic subtype had the worst prognosis and MGAM SNV extent. Compared with the cholesterogenic subgroup, the glycolytic subgroup had higher rates of DDR2 and TPR CNV and higher proliferation scores and MK167 expression levels, but a lower tumor purity proportion. We constructed a forty-four-gene predictive signature and identified MST-321, SB-743921, Neuronal Differentiation Inducer III, romidepsin, vindesine, and YM-155 as high-sensitive drugs for high-risk SKCM patients. CONCLUSIONS: Subtyping SKCM patients via glycolytic and cholesterogenic genes was effective, and patients in the glycolytic-gene enriched group were found to have the worst outcome. A robust prognostic algorithm was developed to enhance clinical decisions in relation to drug administration.

LncRNA HAND2-AS1 exerts anti-oncogenic effects on bladder cancer via restoration of RARB as a sponge of microRNA-146.

BACKGROUND: Growing evidence has shown that long noncoding RNA: microRNA: mRNA is implicated in tumor initiation, development, and progression. Long noncoding RNA HAND2-AS1 exhibits anti-cancer effects in diverse cancers. However, the knowledge of HAND-AS1 in bladder cancer development remains unknown. METHODS: LncRNA and miRNA microarray was conducted to explore different expressed RNA in primary bladder cancer specimens. RNA-RNA interaction prediction tools miRcode ( http://www.mircode.org/ ), DIANA-lncBase v2 ( https://carolina.imis.athena-innovation.gr/diana_tools/web/index.php?r=lncbasev2%2Findex-experimental ), DIANA-TarBase v.8 ( https://carolina.imis.athena-innovation.gr/diana_tools/web/index.php?r=tarbasev8%2Findex ) and miRDB ( http://www.mirdb.org/ ) were employed to predict the interactions between RNA. Bladder cancer cell lines were used to perform cell proliferation and apoptosis assays. Western blot and quantitative Real-time Polymerase Chain Reaction were used to determine the expression of protein and RNA separately. Dual-luciferase assay was conducted to determine the activity of three prime untranslated region of retinoic acid receptor beta (RARB). Furthermore, 5637 human bladder cancer mouse models were established to investigate the interactions of lncRNA: miRNA: mRNA in vivo. RESULTS: Based on the RT2 lncRNA PCR Arrays analysis, we validated HAND2-AS1 declined in bladder cancer and negatively correlated with the depth of invasion and grades. The overexpression of HAND2-AS1 in human bladder cancer cells 5637 and RT4 hampered cell proliferation by provoking Caspase 3-triggered cell apoptosis. Besides, one of the HAND2-AS1 sponges, miR-146, elevated in bladder cancer and targeted the tumor suppressor, retinoic acid receptor beta (RARB). We further demonstrated that the HAND2-AS1: miR-146: RARB complex promoted Caspase 3-mediated apoptosis by suppressing COX-2 expression. Finally, the results gained in mouse xenografts suggested that HAND2-AS1 diminished miR-146 expression, thereby reversing the suppression of miR-146 on RARB-mediated apoptosis and contributing to bladder cancer regression. CONCLUSION: The present study sheds light on the fact that lncRNA HAND2-AS1 exerted as a tumor suppressor by releasing RARB from miR-146, leading to tumor proliferation and invasion inhibition. The findings expanded HAND2-AS-mediated regulatory networks' knowledge and provided novel insights to improve the RARB-targeted regimens against bladder cancer.

Establishment of Novel Prostate Cancer Risk Subtypes and A Twelve-Gene Prognostic Model.

Prostate cancer (PCa) is the most common malignancy among men worldwide. However, its complex heterogeneity makes treatment challenging. In this study, we aimed to identify PCa subtypes and a gene signature associated with PCa prognosis. In particular, nine PCa-related pathways were evaluated in patients with PCa by a single-sample gene set enrichment analysis (ssGSEA) and an unsupervised clustering analysis (i.e., consensus clustering). We identified three subtypes with differences in prognosis (Risk_H, Risk_M, and Risk_L). Differences in the proliferation status, frequencies of known subtypes, tumor purity, immune cell composition, and genomic and transcriptomic profiles among the three subtypes were explored based on The Cancer Genome Atlas database. Our results clearly revealed that the Risk_H subtype was associated with the worst prognosis. By a weighted correlation network analysis of genes related to the Risk_H subtype and least absolute shrinkage and selection operator, we developed a 12-gene risk-predicting model. We further validated its accuracy using three public datasets. Effective drugs for high-risk patients identified using the model were predicted. The novel PCa subtypes and prognostic model developed in this study may improve clinical decision-making.

Immune-Related Gene-Based Novel Subtypes to Establish a Model Predicting the Risk of Prostate Cancer.

BACKGROUND: There is significant heterogeneity in prostate cancer (PCa), but immune status can reflect its prognosis. This study aimed to explore immune-related gene-based novel subtypes and to use them to create a model predicting the risk of PCa. METHODS: We downloaded the data of 487 PCa patients from The Cancer Genome Atlas (TCGA) database. We used immunologically relevant genes as input for consensus clustering and applied survival analysis and principal component analysis to determine the properties of the subtypes. We also explored differences of somatic variations, copy number variations, TMPRSS2-ERG fusion, and androgen receptor (AR) scores among the subtypes. Then, we examined the infiltration of different immune cells into the tumor microenvironment in each subtype. We next performed Gene Set Enrichment Analysis (GSEA) to illustrate the characteristics of the subtypes. Finally, based on the subtypes, we constructed a risk predictive model and verified it in TCGA, Gene Expression Omnibus (GEO), cBioPortal, and International Cancer Genome Consortium (ICGC) databases. RESULTS: Four PCa subtypes (C1, C2, C3, and C4) were identified on immune status. Patients with the C3 subtype had the worst prognosis, while the other three groups did not differ significantly from each other in terms of their prognosis. Principal component analysis clearly distinguished high-risk (C3) and low-risk (C1 + 2 + 4) patients. Compared with the case in the low-risk subtype, the Speckle-type POZ Protein (SPOP) had a higher mutation frequency and lower transcriptional level in the high-risk subtype. In C3, there was also a higher frequency of copy number alterations (CNA) of Clusterin (CLU) and lower CLU expression. In addition, C3 had a higher frequency of TMPRSS2-ERG fusion and higher AR scores. M2 macrophages also showed significantly higher infiltration in the high-risk subtype, while CD8+ T cells and dendritic cells had significantly higher infiltration in the low-risk subtype. GSEA revealed that MYC, androgen, and KRAS were relatively activated and p53 was relatively suppressed in high-risk subtype, compared with the levels in the low-risk subtype. Finally, we trained a six-gene signature risk predictive model, which performed well in TCGA, GEO, cBioPortal, and ICGC databases. CONCLUSION: PCa can be divided into four subtypes based on immune-related genes, among which the C3 subtype is associated with a poor prognosis. Based on these subtypes, a risk predictive model was developed, which could indicate patient prognosis.

Long Non-coding RNA CCAT1 Acts as an Oncogene and Promotes Sunitinib Resistance in Renal Cell Carcinoma.

Although sunitinib contributes to prolonging the progression-free survival of metastatic renal cell carcinoma significantly, the universal presence of resistance limits the initial response rate and restricts durable responses. The mechanisms involved in sunitinib resistance vary and need further investigation. We found long non-coding RNA (lncRNA) colon cancer-associated transcript-1 (CCAT1) overexpressed in sunitinib-resistant cells while declined in the parental cells. Moreover, lncRNA CCAT1 increased significantly in samples with resistance to sunitinib compared with those with responses to sunitinib. The reduction of CCAT1 suppressed cell growth and colony formation while triggering apoptosis. Inversely, the ectopic expression of c-Myc reversed the inhibition of cell growth and enhancement of apoptosis by the knockdown of CCAT1. We also verified that anti-apoptosis protein B-cell lymphoma 2 (Bcl-2) and myeloid cell leukemia 1 (Mcl-1) decreased along with the deregulation of CCAT1, whereas the expression of Bcl-2 and Mcl-1 restored in cells that were transfected sh-CCAT1 and c-Myc simultaneously. Apart from the in vitro experiments, we demonstrated that knockdown of CCAT1 boosted response to sunitinib by performing sunitinib-resistant ACHN mouse models. Briefly, lncRNA CCAT1 conferred renal cell carcinoma resistance to sunitinib in a c-Myc-dependent manner, providing a novel target for improvement of sunitinib therapy.

An overview of advances in multi-omics analysis in prostate cancer.

Prostate cancer (PCa) is a deadly disease for men, and studies of all types of omics data are necessary to promote precision medicine. The maturity of sequencing technology, the improvements of computer processing power, and the progress achieved in omics analysis methods have improved research efficiency and saved research costs. The occurrence and development of PCa is due to multisystem and multilevel pathological changes. Although omics research at a single level is important, this approach often has limitations. In contrast, the combined analysis of multiple types of omics data can better analyze PCa changes as a whole, thus ensuring the validity of research results to the greatest extent. This paper introduces the applications of single omics in PCa and then summarizes research progress in the combined analysis of two or more types of omics data, so as to systematically and comprehensively analyze the necessity of combined analysis of multiple omics data in PCa.

δ-Catenin regulates proliferation and apoptosis in renal cell carcinoma via promoting ß-catenin nuclear localization and activating its downstream target genes.

δ-Catenin is a unique member of the catenin family and is proved to be overexpressed in diverse human cancer types. However, the clinical significance and underling mechanism of δ-catenin expression in renal cell carcinoma (RCC) remain elusive. Herein, we detected the protein expression of δ-catenin in 28 clinical specimens of paired renal cancer tissues and normal renal tissues by Western blot analysis. δ-Catenin expression in 58 cases of renal cell carcinoma was also examined by immunohistochemistry, and its association with clinicopathological factors was analyzed by statistical analysis. In vitro and in vivo assays were employed to further explore the biological role of δ-catenin in RCC. The results showed that δ-catenin was highly expressed in both clinical samples and cell lines of RCC. RCC patients with higher δ-catenin expression had a more advanced pTNM stage and tumor stage as well as lymph nodes metastasis than those with lower expression. By regulating the nuclear translocation of ß-catenin and ß-catenin-mediated oncogenic signals, δ-catenin promoted proliferation and inhibited apoptosis in RCC. In vivo assay indicated δ-catenin facilitated tumor growth in ACHN cell xenograft mouse model. Taken together, our study suggests that δ-catenin might be considered as a novel prognostic indicator and actionable target for gene therapy in renal cell carcinoma.

Circular RNA circ_001621 promotes osteosarcoma cells proliferation and migration by sponging miR-578 and regulating VEGF expression.

Strategies targeted vascular endothelial growth factor (VEGF)-dependent osteosarcoma progression are limited although important progress has been made in illustrating the mechanisms. Here we identified circ_001621 as one of the significantly upregulated circular RNAs (circRNAs) by circRNAs microarrays. We found that patients with high circ_001621 expression had a shorter survival time. Moreover, we found several potential sponge micro RNAs (miRNA) of circ_001621 with Circular RNA Interactome database. Among the candidate sponge, we elucidated the association of circ_001621 and miR-578. In addition, we demonstrated that miR-578 targeted circ_001621 directly. Functionally, we set up the experimental system to investigate the effects of circ_001621/miR-578/VEGF interaction in vitro and in vivo. Results indicated circ_001621-promoted osteosarcoma proliferation and migration via attenuating the inhibition of cyclin-dependent kinase 4 (CDK4) and matrix metallopeptidase 9 (MMP9) by miR-578, respectively. Nude mice experiment was further performed to estimate the promotion of metastasis by circ_001621. The present study evaluated the mechanisms underlying circ_001621 enhanced osteosarcoma progression and provided novel therapeutic targets for advanced osteosarcoma.

Sulfated polysaccharide of Sepiella maindroni ink targets Akt and overcomes resistance to the FGFR inhibitor AZD4547 in bladder cancer.

Rapid appearance of resistance to fibroblast growth factor receptor (FGFR) inhibitors hampers targeted regimens in bladder cancer. In the present study, we evaluated whether SIP-SII, a sulphated derivative of the polysaccharide in Sepiella maindroni (spineless cuttlefish) ink used in traditional Chinese medicine, could attenuate resistance to FGFR inhibition in bladder cancer cells. In vitro assays indicated that SIP-SII reduced cell viability and migration, restricted cell cycle progression, and increased apoptosis in parallel with decreased AKT phosphorylation and downregulation of CDK4, MMP2, and Bcl-2 in RT112 and JMSU1 cells. Synergistic effects on cell viability were observed when SIP-SII was combined with the small-molecule FGFR inhibitor AZD4547. Specific Akt targeting by SIP-SII was suggested by the fact that neither Akt knockdown nor the selective PI3K inhibitor BKM120 enhanced the inhibitory effects of SIP-II, while expression of a constitutively active Akt mutant rescued SIP-SII effects. Furthermore, subcutaneous transplantation of RT112 xenografts confirmed the superiority and tolerability of combined SIP-SII and AZD4547 administration over monotherapy regimens. The present study thus provides pre-clinical evidence of the ability of SIP-SII to improve FGFR-targeted therapies for bladder cancer by inhibiting Akt.