Kiwifruit resistance to gray mold is enhanced by yeast-induced modulation of the endophytic microbiome.

The influence of endophytic microbial community on plant growth and disease resistance is of considerable importance. Prior research indicates that pre-treatment of kiwifruit with the biocontrol yeast Debaryomyces hansenii suppresses gray mold disease induced by Botrytis cinerea. However, the specific underlying mechanisms remain unclear. In this study, Metagenomic sequencing was utilized to analyze the composition of the endophytic microbiome of kiwifruit under three distinct conditions: the healthy state, kiwifruit inoculated with B. cinerea, and kiwifruit treated with D. hansenii prior to inoculation with B. cinerea. Results revealed a dominance of Proteobacteria in all treatment groups, accompanied by a notable increase in the relative abundance of Actinobacteria and Firmicutes. Ascomycota emerged as the major dominant group within the fungal community. Treatment with D. hansenii induced significant alterations in microbial community diversity, specifically enhancing the relative abundance of yeast and exerting an inhibitory effect on B. cinerea. The introduction of D. hansenii also enriched genes associated with energy metabolism and signal transduction, positively influencing the overall structure and function of the microbial community. Our findings highlight the potential of D. hansenii to modulate microbial dynamics, inhibit pathogenic organisms, and positively influence functional attributes of the microbial community.

DNA-functionalized artificial mechanoreceptor for de novo force-responsive signaling.

Synthetic signaling receptors enable programmable cellular responses coupling with customized inputs. However, engineering a designer force-sensing receptor to rewire mechanotransduction remains largely unexplored. Herein, we introduce nongenetically engineered artificial mechanoreceptors (AMRs) capable of reprogramming non-mechanoresponsive receptor tyrosine kinases (RTKs) to sense user-defined force cues, enabling de novo-designed mechanotransduction. AMR is a modular DNA-protein chimera comprising a mechanosensing-and-transmitting DNA nanodevice grafted on natural RTKs via aptameric anchors. AMR senses intercellular tensile force via an allosteric DNA mechano-switch with tunable piconewton-sensitive force tolerance, actuating a force-triggered dynamic DNA assembly to manipulate RTK dimerization and activate intracellular signaling. By swapping the force-reception ligands, we demonstrate the AMR-mediated activation of c-Met, a representative RTK, in response to the cellular tensile forces mediated by cell-adhesion proteins (integrin, E-cadherin) or membrane protein endocytosis (CI-M6PR). Moreover, AMR also allows the reprogramming of FGFR1, another RTK, to customize mechanobiological function, for example, adhesion-mediated neural stem cell maintenance.

Pathogenic fungi shape the fungal community, network complexity, and pathogenesis in kiwifruit.

Kiwifruit decay caused by endophytic fungi is affected by exogenous pathogens that trigger changes in fungal community composition and interact with the endophytic fungal community. Four fungal pathogens of kiwifruit were identified. These were Aspergillus japonicus, Aspergillus flavus, Botryosphaeria dothidea, and Penicillium oxalicum. Except for P. oxalicum, the remaining three species represent newly described pathogens of kiwifruit. All four fungal species caused disease and decay in mature kiwifruit. Results of the fungal community analysis indicated that three pathogens that A. japonicus, A. flavus and P. oxalicum were the most dominant, however, other fungal species that did not cause disease symptoms were also present. Positive interactions between fungal species were found in asymptomatic, symptomatic, and infected kiwifruit. The ability of all four pathogens to infect kiwifruit was confirmed in an inoculation experiment. The presence of any one of the four identified pathogens accelerated decay development and limited the postharvest longevity of harvested kiwifruit. Results of the study identified and confirmed the ability of four fungal species to infect and cause decay in harvested kiwifruit. Changes in the structure and composition of the kiwifruit microbiome during the decay process were also characterized. This provides a foundation for the further study of the microbiome of kiwifruit and their involvement in postharvest diseases.

Low-dose graphene oxide promotes tumor cells proliferation by activating PI3K-AKT-mTOR signaling via cellular membrane protein integrin αV.

Along with the increasing production and application of graphene oxide (GO), its environmental health and safety (EHS) risks have become a global concern. Numerous studies have investigated the biosafety and toxicity mechanisms associated with GO, however, the majority of previous studies were based on its direct toxic dose, which could not reflect the realistic state of environmental exposure of GO with an indirect toxic dose (low dose). Meanwhile, the effects of low-dose GO on the progression of tumors are still unclearly. Herein, we found that GO can promote multiple types of tumor cell proliferation under its low-dose treatment. Moreover, the lateral size of GO has no obvious distinction on its promoting effect on tumor proliferation. The mechanistic investigation revealed that low-dose GO treatment increased the expression level of integrin αV protein, a cell membrane receptor, and further lead to the constitutively activated PI3K/AKT/mTOR signaling pathway and promoted mitotic progression. Collectively, these findings increased our understanding of the detrimental effects of GO in promoting tumor proliferation, as well as improved our biosafety assessment at its realistic exposure doses.

Linggui Zhugan Decoction activates the SIRT1-AMPK-PGC1α signaling pathway to improve mitochondrial and oxidative damage in rats with chronic heart failure caused by myocardial infarction.

Objective: To investigate the effects of Linggui Zhugan Decoction on mitochondrial and oxidative damage in rats with chronic heart failure after myocardial infarction and the related mechanisms. Methods: Chronic heart failure after myocardial infarction was established by coronary artery ligation. Heart failure rats were randomly divided into three groups: Model group (n = 11), Linggui Zhugan Decoction group (n = 12), and captopril group (n = 11). Rats whose coronary arteries were only threaded and not ligated were sham group (n = 11). Cardiac function, superoxide dismutase (SOD), malondialdehyde (MDA) contents, soluble growth-stimulating expression factor (ST2), and N-terminal B-type brain natriuretic peptide precursor (NTproBNP) levels were analyzed after treatment. Moreover, the level of mitochondrial membrane potential was detected by JC-1 staining, the ultrastructural of myocardial mitochondria were observed by transmission electron microscopy. The related signal pathway of silent information regulator factor 2-related enzyme 1 (SIRT1), adenylate activated protein kinase (AMPK), phosphorylated adenylate activated protein kinase (p-AMPK), and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is an important pathway to regulate mitochondrial energy metabolism, and to initiate mitochondrial biogenesis. The expression level was detected by Western blot and reverse transcription to explore the mechanism of the decoction. Results: Compared with the model rats, Linggui Zhugan Decoction significantly improved cardiac function (p < 0.05), reduced MDA production (p < 0.01), increased SOD activity (p < 0.05), reduced ST-2(p < 0.01), and NT-proBNP(p < 0.05) levels, increased mitochondrial membrane potential, and improved mitochondria function. In addition, Linggui Zhugan Decoction upregulated the expression of SIRT1, p-AMPK, PGC-1α protein, and mRNA in cardiac myocytes. Conclusion: Linggui Zhugan Decoction can improve the cardiac function of heart failure rats by enhancing myocardial antioxidant capacity and protecting the mitochondrial function, the mechanism is related to activating SIRT1/AMPK/PGC-1α signaling pathway.

The impact of histological variants in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy.

OBJECTIVE: To investigate the impact of histological variants (HV) in patients with upper tract urothelial carcinoma (UTUC) and analyze the potential association between HV and postoperative bladder recurrence. MATERIALS AND METHODS: The medical records of UTUC patients treated with RNU at our center from January 2012 to December 2019 were retrospectively analyzed. Patients were grouped according to the types of HV. Clinicopathological features and prognostic factors were compared among groups. RESULTS: A total of 629 patients were included in the study: 458 (73%) patients had pure urothelial carcinoma (PUC) and 171 (27%) patients had UTUC with HV. Squamous differentiation was the most common type (124 cases, 19%), followed by glandular differentiation (29 cases, 5.0%). Patients with HV had a higher proportion of T3 and T4 pathologic stages (P < 0.001) as well as high-grade disease (P = 0.002). In the univariate analysis, squamous differentiation and glandular differentiation were significantly associated with worse cancer-specific survival (CSS) (HR 2.22, 95% CI 1.62-3.04, P < 0.001; HR 1.90, 95% CI 1.13-3.20, P = 0.016). However, the multivariate analysis showed that this association became non-significant. We found that HV were associated with recurrent muscle-invasive bladder cancer (MIBC) after RNU and all patients had T2 and T3 initial tumor stages (P = 0.008, P < 0.001). CONCLUSION: We found that UTUC patients with HV were associated with biologically aggressive disease and recurrent MIBC after RNU. The detection of bladder recurrence following surgery needs to be given more attention in advanced UTUC patients with HV.

The dependences of mesenchymal stem cells commitments on the size, concentration, internalization and exposure time of Iron Oxide Nanoparticles through F-actin, Lamin A and ROS.

Though magnetic iron oxide nanoparticles (IONPs) are approved for clinical use as contrast agents for MR imaging in United States and Europe, and are widely used to label cells in research, the relationship between IONPs and mesenchymal stem cells (MSCs) is not fully addressed. Here the effects of consistently appeared γ-Fe2 O3 on the lineage commitment of MSCs were studied to optimize applications of IONPs in MSCs upon verification of viability. 30 nm 10 µg/mL induced highest promotions on osteogenesis, while 30 and 50 nm of 100 µg/mL elicited most chondrogensis in 14 days, where the effects on ALP, GAG and SOX9 appeared after 7 days, while on RUNX2 came out after 10 days. γ-Fe2 O3 enhanced intracellular and extracellular Fe3+ and ROS, modulated F-actin and decreased Lamin A of MSCs at different time scale. The disturbances of F-actin, Lamin A or ROS altered the effects of γ-Fe2 O3 on MSC differentiation. Our results demonstrate that different size, concentration and modulation of γ-Fe2 O3 are needed in its MSC applications for bone and cartilage tissues. Furthermore, an undocumented phenomenon that the modulation of F-actin affected the Lamin A expression in MSCs was observed.

Analysis of the Efficacy of Multidrug Combination Chemotherapy Regimens for Osteosarcoma and the Management of Chemotherapeutic Reactions.

Purpose: To analyse the efficacy of high-dose methotrexate + adriamycin + cisplatin (HD-MTX + ADR + PDD, MAP) regimens applied to osteosarcoma and the pretreatment and resolution of chemotherapeutic reactions. Methods: The clinical data of 21 patients with osteosarcoma in our hospital from January 2015 to January 2018 were retrospectively analysed. All patients were treated with the MAP protocol, 21 days for 1 cycle, and treated with artificial joint replacement or amputation after 3∼4 cycles of treatment. The tumour tissue necrosis rate, limb preservation success rate after treatment, and chemotherapy response during chemotherapy were counted and analysed for all patients. A local recurrence rate, a distant metastasis rate, and an overall survival rate were recorded during the 3-year follow-up period. Results: After treatment, the percentage of tumour tissue necrosis ≥90% was 85.71% (18/21) and the percentage of successful limb preservation was 57.14% (12/21) in 21 patients with osteosarcoma. During chemotherapy, all 21 patients with osteosarcoma experienced various degrees of chemotherapy reactions, mainly bone marrow suppression of 100% (21/21), gastrointestinal reactions of 100% (21/21), liver function impairment of 66.67% (14/21), and cardiotoxicity of 52.38% (11/21), all of which improved and completed treatment after treatment. During the 3-year follow-up period, the 21 patients with osteosarcoma had a local recurrence rate of 9.52% (2/21), a distant metastasis rate of 28.57% (6/21), and an overall survival rate of 80.95% (17/21). Conclusion: With stringent protection and relief measures, patients with osteosarcoma treated with the MAP regimen have promising near-term outcomes, with high survival rates over 3 years and tolerable chemotherapy responses. The clinical trial is registered under L2015093.

The CUSUM curve combined with comprehensive complication index for assessing short-term complications of radical cystectomy.

OBJECTIVE: To evaluate the comprehensive complication index(CCI) and Clavien-Dindo classification(CDC) for short-term postoperative complications in radical cystectomy and assess cumulative surgical morbidity to compare sufficient surgical skill. METHODS: From September 30, 2010, to October 1, 2020, clinical data of patients with urothelial carcinoma who underwent radical cystectomy with urinary diversion were gathered, patients who had only a urinary diversion, bladder sparing surgery, additional abdominal surgeries at the same time were all excluded. The CDC and CCI were utilized to evaluate 30-d complications after radical cystectomy and the relevance of hospital stay was compared between CCI and CDC. The cumulative sum control models (CUSUM) were used to evaluate the overall surgical morbidity of radical cystectomy in our facility and for comparisons between surgeons. RESULTS: This study enrolled a total of 635 individuals, 548 (86.3%) of whom had 1124 problems. The incidence of severe complications (CDC≥ Grade III) was 10.2%. The average CCI was 20.2 ± 14.7. Gender, urinary diversion subtype, procedure method, and surgeon were significantly correlated with the increase of CCI (p < 0.05). The CCI demonstrated a better relationship with hospital stay (R2  = 0.429) than the CDC (R2  = 0.361). The CUSUM-CCI model demonstrated a difference and growth distribution in dynamic time between individual surgeons. CONCLUSIONS: CCI can better reflect the incidence of complications for radical cystectomy than CDC, and CCI is more strongly correlated with postoperative hospital stay. The CUSUM-CCI model can reflect the quality of surgical skill for each surgeon instantaneously.

Primitive neuroectodermal tumor of the prostate in a 58-year-old man: A case report.

BACKGROUND: Primitive neuroectodermal tumor (PNET), especially located in the prostate, is a rare tumor that mainly occurs in young men. Bladder or rectum invasion and distant metastasis are strongly associated with a poor prognosis. Combination therapy, including radical surgery, adjuvant chemotherapy, and radiotherapy, is available. We present a case of prostatic PNET and a review of 17 cases identified in the literature. CASE SUMMARY: A 58-year-old man was admitted complaining of dysuria for 2 years. Computed tomography and magnetic resonance imaging showed a large cystic-solid mass in the pelvic cavity compressing the surrounding bladder and rectum. The mass was iso- to hyperintense on T1-weighted imaging (WI) and heterogeneously hyperintense on T2WI. Cystic degeneration and necrosis were seen in the tumor, and solid tissues within the mass enhanced on contrast-enhanced scan. The patient underwent robot-assisted laparoscopic pelvic tumor resection. Histologically, the presence of many small round cells that were positive for expression of CD99, vimentin, and synaptophysin established the diagnosis of PNET in the prostate after surgery. The patient underwent adjuvant chemotherapy. During 34 mo of follow-up, the patient had no signs or symptoms of recurrence or residual disease. CONCLUSION: We present the case of the oldest prostatic PNET patient, who has a good prognosis. This illustrates how older men with prostatic PNET may also benefit from the combination therapy, like younger adults, and achieve a long-term survival. As always, PNET should be considered in the differential diagnosis of aggressive prostatic tumors in young men.

Sarcopenia as an independent predictor for venous thromboembolism events in bladder cancer patients undergoing radical cystectomy.

BACKGROUND: Sarcopenia has been proved to be related to the prognosis of patients with bladder cancer (BC) after radical cystectomy (RC). The relationship between sarcopenia and the occurrence of venous thromboembolism (VTE) after RC is unclear. METHODS: We collected data of 252 BC patients treated with RC at our institution. Data was obtained from the electronic medical record database. Sarcopenia was defined by the third lumbar vertebra skeletal muscle index (SMI) which was measured using preoperative computed tomography. The primary outcome was the incidence of VTE within 30 days after the surgery in sarcopenia and non-sarcopenia groups. Outcomes between the two cohorts were compared using univariate analysis. Multivariate logistic regression was used to control for differences between cohorts. RESULTS: Two hundred fifty-two patients were enrolled, of which 85 (33.7%) patients were in sarcopenia group, while 167 (66.3%) patients were not in sarcopenia group. The incidence of total VTE in sarcopenia group was higher than that in the extended group (10.6% vs. 1.8%, p = 0.005). Sarcopenia did not cause an increase in other postoperation 30 days complications (all p > 0.05). Multivariate analysis confirmed sarcopenia was independently associated with increased odds of VTE (OR = 4.18, 95% CI [1.01-17.27]; p = 0.048). Subgroup analysis showed that patients with VTE tended to be older (76.5 vs 66.0, p = 0.025) and have higher proportion of diabetes (58.3% vs 14.2%, p < 0.001) as well as lower level of serum albumin (35.0 g/L vs 40.4 g/L, p = 0.023) compared with those without VTE. CONCLUSIONS: Sarcopenia was an independent predictor for VTE with patients undergoing RC for BC.

Synthesis, Properties, and Regioselective Functionalization of 9,9a-BN Anthracene.

A novel 9,9a-BN anthracene 5 has been synthesized by the Ru-catalyzed electrocyclization of BN-aromatic enynes. The photophysical properties of 5 are different from those of all-carbon anthracene and other reported BN-anthracenes. The reactivity of 5 has been investigated by treating 5 with organolithium compounds, Br2, or N-iodosuccinimide. The resulting halogenated compounds can be easily functionalized via cross-coupling reactions. UV-vis and fluorescence spectroscopy of 5 have been investigated to explore the photophysical properties of these BN-anthracenes.

Flexible cystoscopy can improve anxiety and subjective feelings of bladder cancer patients during follow-up.

INTRODUCTION: The effect of repeated cystoscopy on bladder cancer (BC) patient anxiety and feelings is rarely evaluated. AIM: To compare the difference of patients' anxiety and subjective feelings caused by different cystoscopes. MATERIAL AND METHODS: We prospectively included 192 BC patients who accepted regular cystoscopy follow-up after transurethral resection of bladder tumor (TURBT): 93 in the flexible group and 99 in the rigid group. The method of anesthesia and the order of examinations were consistent between different groups. We analyzed the anxiety level before cystoscopy, the maximum pain during the examination and the change of lower urinary tract symptoms (LUTS) before and after cystoscopy. Meanwhile, we analyzed the rate of gross hematuria and pyuria after cystoscopy. The anxiety and pain levels were evaluated by the Amsterdam Preoperative Anxiety and Information Scale (APAIS) and visual analogue scale (VAS). LUTS was reflected by the Core Lower Urinary Tract Symptom Score (CLSS). We distinguished gender during analysis. RESULTS: The median APAIS score of male patients undergoing flexible or rigid cystoscopy was 8 vs. 12 (p < 0.01), and this result for females was 8 vs. 9 (p = 0.048). The median pain scores for men in the two groups was 1 vs. 2 (p < 0.01), respectively, and this outcome in female patients was 0 vs. 1 (p < 0.01). Patients in the rigid group had more CLSS change (0 vs. 1, p < 0.01). There was no difference in pyuria or gross hematuria rate after examination. Analysis in respective groups showed that men have more severe pain than women, 1 vs. 0 (p = 0.001) in the flexible group and 2 vs. 1 (p = 0.009) in the rigid group. CONCLUSIONS: A flexible cystoscope can improve anxiety and subjective feelings of BC patients during cystoscopy follow-up.

A Modified Triangular Osteosynthesis Protocol for the Rod and Pedicle Screw Fixation of Vertical Unstable Sacral Fractures.

BACKGROUND: The stabilization of vertical unstable sacral fractures has been a complex problem that is a challenge to current standard approaches. Here, we attempted to evaluate a modified technique for sacral fractures. METHODS: In the modified triangular osteosynthesis technique, we adopted a vertical and transverse fixation with a rod and pedicle screw system to reduce and fix sacral fractures in 28 subjects. The postsurgery effect of this technique was evaluated by physical examination and radiography. RESULTS: In the postoperative day 1, the patients were able to move body position passively from the lateral side to supine and exercise their legs by themselves. After a follow up of 20 months, radiological evaluation showed that fracture fragment reduction was excellent in 18 (64%), good (displacement 5-10 mm) in 8 (29%), and fair (displacement 10-15 mm) in 2 (7%) patients. Three patients with a preoperative perineal neurological impairment had a complete recovery after surgical decompression. All patients had achieved bone union of fractures, and no loss of fracture reduction was detected. CONCLUSIONS: The modified procedures offered an easier approach to fix vertical unstable sacral fractures, thereby achieving quicker and stable functionality. This suggests an alternative approach to manage unstable sacral fractures. LEVEL OF EVIDENCE: 4. CLINICAL RELEVANCE: The stabilization of vertical unstable sacral fractures has been a complex problem that is a challenge to current standard approaches. We attempted to introduce a modified technique for sacral fractures.

Immobilization of polyphenol oxidase on chitosan/organic rectorite composites for phenolic compounds removal.

Chitosan/organic rectorite (CTS/OREC) composites were prepared and characterized by Fourier transform infrared spectrometry and X-ray diffraction. Polyphenol oxidase (PPO) was immobilized on CTS/OREC by physical adsorption (APPO) and covalent binding (CPPO). Taguchi method was applied in the optimization of immobilization conditions resulting in the highest enzyme activity of 16.37 × 103 and 8.92 × 103U/g for APPO and CPPO, respectively. APPO enzyme activity was higher than that of CPPO, while CPPO showed the higher enzyme loading capacity than that of APPO. The removal percentage of phenolic compound, including phenol (PH), 4-chlorophenol (4-CP) and 2,4-dichlorophenol (2,4-DCP), by immobilized PPO was also explored. The results indicated that APPO was more efficient in phenolic compounds removal than CPPO. APPO contributed to a quick removal in the first hour, and the removal percentage of PH, 4-CP and 2,4-DCP could reach 69.3 ± 4.2%, 89.8 ± 2.5% and 93.8 ± 1.7% within 2 h, respectively. The order of removal percentage of phenolic compounds for both immobilized PPO was 2,4-DCP > 4-CP > PH. After 10 consecutive operations, the removal percentage of 2,4-DCP reached 73.2 ± 2.6% and 60.3 ± 1.5% for APPO and CPPO, respectively. The results introduced a novel support for PPO immobilization, and the immobilized PPO had great potential in wastewater treatment.

Expression and Prognostic Significance of the MMP Family Molecules in Bladder Cancer.

BACKGROUND: Bladder cancer (BC) is the 10th most common cancer worldwide with significantly varied prognosis in different pathological subtypes. MMPs, a group of enzymes, could involve in the invasion and metastasis of numerous malignancies. The function of MMPs in BC is partly reported in several studies but with great conflicts; hence, a systematic analysis of expression levels and prognostic values of these MMP genes are still to be determined. METHODS: Firstly, differentially expressed genes (DEGs) of MMPs were identified in ONCOMINE, GEPIA, and UALCAN databases, and these DEGs were also detected by real-time RT-qPCR. More importantly, we investigated the clinical significance of these DEGs in BC patients via Kaplan- Meier (KM) Plotter, UALCAN, and cBioPortal databases. RESULTS: The study found that the mRNA expression of MMP1/11 in BC samples was significantly higher than that in normal bladder tissues, and MMP2/3 was lower in the former than in the latter. The expression level of MMP1/2/7/9/11/13/23B was significantly related to the tumor stages. Furthermore, the prognostic analysis suggested that the high transcription levels of MMP7 and low transcription levels of MMP23A were correlated with favorable relapse-free survival and overall survival in the patients with BC, respectively. Notably, high MMP11/13 expression levels indicated poor overall survival (OS) and relapse-free survival (RFS) in patients with BC. CONCLUSION: This study revealed that MMP1/2/3/7/9/11/13/23A/23B are possible prognostic biomarkers and clinical therapeutic targets for patients with BC.

Long noncoding RNAs, ENST00000598996 and ENST00000524265, are correlated with favorable prognosis and act as potential tumor suppressors in bladder cancer.

Bladder cancer (BC) is a serious malignancy worldwide due to its distant metastasis and high recurrence rates. Increasing evidence has indicated that dysregulated long non­coding RNAs (lncRNAs) are involved in tumorigenesis and progression in multiple malignancies. However, their clinical significances, biological functions and molecular mechanisms in BC remain poorly understood. Hence, the present study investigated the expression profile of lncRNAs and mRNAs in five BC tissues and the corresponding adjacent normal specimens using high­throughput RNA sequencing (RNA­seq). A total of 103 differentially expressed (DE) lncRNAs were identified, including 35 upregulated and 68 downregulated ones in BC tissues. Similarly, a total of 2,756 DE­mRNAs were detected, including 1,467 upregulated and 1,289 downregulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses, and lncRNA­miRNA­mRNA network analyses suggested that these dysregulated lncRNAs are potentially implicated in the onset and progression of BC. Subsequently, four lncRNAs (upregulated ENST00000433108; downregulated ENST00000598996, ENST00000524265 and ENST00000398461) and two mRNAs (upregulated CCNB1 and CDK1) in 64 pairs of BC and adjacent normal tissues and four BC cell lines were detected using reverse transcription­quantitative PCR and these results were consistent with the sequencing data. Additionally, Fisher's exact test, Kaplan­Meier plots, and Cox regression analyses were used for elucidating the clinical values of ENST00000598996 and ENST00000524265. Furthermore, a receiver operating characteristic curve was constructed to assess their diagnostic values. The low expression level of ENST00000598996 and ENST00000524265 was correlated with unfavorable clinicopathological parameters, and shorter progression­free and overall survival time, whereas, ENST00000433108 was not associated with either. The in vitro functional experiments also revealed that the overexpression of ENST00000598996 and ENST00000524265 decreased the proliferation, migration, and invasion abilities of BC cells. Collectively, the results of the present study provide a novel landscape of lncRNA and mRNA expression profiles in BC. In addition, the results also indicated that ENST00000598996 and ENST00000524265 may serve as tumor suppressors, potential diagnostic biomarkers and prognostic predictors for patients with BC.

Downregulated hsa_circ_0077837 and hsa_circ_0004826, facilitate bladder cancer progression and predict poor prognosis for bladder cancer patients.

Growing evidence has indicated that circular RNAs (circRNAs) play crucial roles in multiple biological processes. However, alterations in circRNA profiles during bladder cancer progression and the clinical significance thereof remain unclear. Therefore, high-throughput RNA sequencing was conducted to identify circRNA and mRNA profiles in five pairs of bladder cancer tissues and adjacent noncancerous tissues. A total of 87 differentially expressed circRNAs and 2756 mRNAs were detected in above bladder cancer samples compared with paired noncancerous samples. Functional enrichment analyses, circRNA-microRNA-mRNA, and protein-protein interaction networks revealed that these dysregulated circRNAs were potentially involved in carcinogenesis and evolution of bladder cancer. Subsequently, the differential expression of eight circRNAs was detected by real-time qPCR. Hsa_circ_0003141 and hsa_circ_0008039 were significantly upregulated as well as hsa_circ_0026782, hsa_circ_0077837, hsa_circ_0004826, and hsa_circ_0001946 were significantly downregulated among validation of 70 matched bladder cancer tissues (≥75%). Moreover, hsa_circ_0077837 and hsa_circ_0004826 were also verified as markedly downregulated in four bladder cancer cells (100%). Naturally, hsa_circ_0077837 and hsa_circ_0004826 were also demonstrated using RNase-R+ resistance experiments. In addition, Fisher's exact test, Kaplan-Meier plots, Cox regression analyses, and receiver operating characteristic curve was performed to assess their clinical value. Downregulation of hsa_circ_0077837 and hsa_circ_0004826 all was significantly correlated with worse clinicopathological features and poor prognosis of bladder cancer patients. The area under the receiver operating characteristic curve of them was 0.775 (P < .0001) and 0.790 (P < .0001), respectively. Not surprisingly, in vitro functional experiments also demonstrated that the overexpression of hsa_circ_0077837 and hsa_circ_0004826 significantly weakened the proliferation, migration, and invasion of bladder cancer cells. Overall, hsa_circ_0077837 and hsa_circ_0004826 might act as tumor suppressors in the bladder cancer progression and serve as a potential biomarker for the diagnosis, prognosis, and therapy of bladder cancer.

Small cell carcinoma of the upper urinary tract and factors associated with progress survival: a systematic review and pooled analysis.

INTRODUCTION: Little is known about small cell carcinoma of the upper urinary tract (UUT-SCC), the aim of this study is to identify the risk factors in relation to survival of patients with UUT-SCC. EVIDENCE ACQUISITION: Literature search on UUT-SCC was performed in databases including MEDLINE, EMBASE, Wangfang, and CNKI. Studies were eligible for inclusion if outcomes of patients with histopathologically confirmed UUT-SCC were reported. The relevant data on clinic, pathology, and therapy were collected. Progress survival was evaluated using the Cox regression model with the robust sandwich estimates of the covariance matrix. EVIDENCE SYNTHESIS: There were 55 eligible publications identified, contributing 76 patients in total. The median of overall survival (OS) was 14 months. In univariable analyses, pathological stage and platinum-based chemotherapy regimen were associated with OS (pT3-pT4 versus pT1-pT2, HR=3.228, P=0.005; other chemotherapies versus platinum-based, HR=6.249, P=0.035). The median of cancer-specific survival (CSS) was 15 months. In univariable analyses, pathological stage and platinum-based chemotherapy regimen were associated with CCS (pT3-pT4 versus pT1-pT2, HR=3.332, P=0.004; non-platinum based versus platinum-based, HR=7.784, P=0.025). CONCLUSIONS: In multivariable analyses, no variables were associated with OS and CSS. UUT-SCC is a rare tumor characterized by an aggressive clinical course. Pathological stage and platinum-based chemotherapy regimen are the most important factors related to OS and CSS.

Synthesis of bis-BN-Naphthalene-Fused Oxepins and Their Photoluminescence Including White-Light Emission.

A series of novel bis-BN-naphthalene-fused oxepin derivatives were synthesized via a Pd-catalyzed tandem reaction from brominated 2,1-borazaronaphthalenes and cis-bis(boryl)alkenes. X-ray crystallographic analysis revealed that bis-BN-naphthalene-fused oxepins feature a planar framework. The electronic and photophysical properties of the novel BN-naphthalene-fused oxepins were investigated by UV-vis and fluorescence spectroscopies and density functional theory (DFT) calculations, which disclosed the distinct electronic and photophysical properties of the analogous hydrocarbon system. Interestingly, dual-fluorescent emissions were observed upon dissolving N-substituted derivatives 10-14 in dimethyl sulfoxide. Tunable emission colors especially for white-light emissions can be achieved by controlling the ratio of solvents, concentration, or temperature using only a single-molecule compound.