Sequence diversity of apidaecin-like peptides arresting the terminating ribosome.

The Proline-rich Antimicrobial Peptide (PrAMP) apidaecin (Api) inhibits translation by binding in the ribosomal nascent peptide exit tunnel, trapping release factors RF1 or RF2, and arresting ribosomes at stop codons. To explore the extent of sequence variations of the native 18-amino acid Api that allows it to preserve its activity, we screened a library of synthetic mutant Api genes expressed in bacterial cells, resulting in nearly 350000 peptide variants with multiple substitutions. By applying orthogonal negative and positive selection strategies, we identified a number of multi-substituted Api variants capable of arresting ribosomes at stop codons. Our findings underscore the critical contribution of specific amino acid residues of the peptide for its on-target function while significantly expanding the variety of PrAMPs acting on the terminating ribosome. Additionally, some of the tested synthesized multi-substituted Api variants exhibit improved antibacterial activity compared to that of the wild type PrAMP and may constitute the starting point to develop clinically useful antimicrobials.

Inhibition of translation termination by the antimicrobial peptide Drosocin.

The proline-rich antimicrobial peptide (PrAMP) Drosocin (Dro) from fruit flies shows sequence similarity to other PrAMPs that bind to the ribosome and inhibit protein synthesis by varying mechanisms. The target and mechanism of action of Dro, however, remain unknown. Here we show that Dro arrests ribosomes at stop codons, probably sequestering class 1 release factors associated with the ribosome. This mode of action is comparable to that of apidaecin (Api) from honeybees, making Dro the second member of the type II PrAMP class. Nonetheless, analysis of a comprehensive library of endogenously expressed Dro mutants shows that the interactions of Dro and Api with the target are markedly distinct. While only a few C-terminal amino acids of Api are critical for binding, the interaction of Dro with the ribosome relies on multiple amino acid residues distributed throughout the PrAMP. Single-residue substitutions can substantially enhance the on-target activity of Dro.

Integrated metabolomic and transcriptomic analyses provide insights into regulation mechanisms during bulbous stem development in the Chinese medicinal herb plant, Stephania kwangsiensis.

BACKGROUND: Stephania kwangsiensis Lo (Menispermaceae) is a well-known Chinese herbal medicine, and its bulbous stems are used medicinally. The storage stem of S. kwangsiensis originated from the hypocotyls. To date, there are no reports on the growth and development of S. kwangsiensis storage stems. RESULTS: The bulbous stem of S. kwangsiensis, the starch diameter was larger at the stable expanding stage (S3T) than at the unexpanded stage (S1T) or the rapidly expanding stage (S2T) at the three different time points. We used ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and Illumina sequencing to identify key genes involved in bulbous stem development. A large number of differentially accumulated metabolites (DAMs) and differentially expressed genes (DEGs) were identified. Based on the differential expression profiles of the metabolites, alkaloids, lipids, and phenolic acids were the top three differentially expressed classes. Compared with S2T, significant changes in plant signal transduction and isoquinoline alkaloid biosynthesis pathways occurred at both the transcriptional and metabolic levels in S1T. In S2T compared with S3T, several metabolites involved in tyrosine metabolism were decreased. Temporal analysis of S1T to S3T indicated the downregulation of phenylpropanoid biosynthesis, including lignin biosynthesis. The annotation of key pathways showed an up-down trend for genes and metabolites involved in isoquinoline alkaloid biosynthesis, whereas phenylpropanoid biosynthesis was not completely consistent. CONCLUSIONS: Downregulation of the phenylpropanoid biosynthesis pathway may be the result of carbon flow into alkaloid synthesis and storage of lipids and starch during the development of S. kwangsiensis bulbous stems. A decrease in the number of metabolites involved in tyrosine metabolism may also lead to a decrease in the upstream substrates of phenylpropane biosynthesis. Downregulation of lignin synthesis during phenylpropanoid biosynthesis may loosen restrictions on bulbous stem expansion. This study provides the first comprehensive analysis of the metabolome and transcriptome profiles of S. kwangsiensis bulbous stems. These data provide guidance for the cultivation, breeding, and harvesting of S. kwangsiensis.

Sall4 Guides p53-Mediated Enhancer Interference upon DNA Damage in Mouse Embryonic Stem Cells.

p53 plays a pivotal role in maintaining the genomic stability of mouse embryonic stem cells (mESCs) through transcriptionally activating and repressing target genes. However, how p53 recognizes its repressed targets remains largely unknown. Herein, we demonstrate that Sall4 negatively regulates DNA damage induced apoptosis (DIA) of mESCs through mediating p53 recruitment to enhancers of ESC-associated genes repressed by p53 from promoters of p53-activated genes. Upon DNA damage, Sall4 is transcriptionally repressed by p53 and plays an anti-apoptotic role without altering p53 activation. Moreover, Sall4 is identified as a novel p53-interacting partner. Consistently, Sall4 exerts its anti-apoptotic function in a p53-dependent manner. Intriguingly, Sall4 depletion not only promotes the transcriptional activation of several p53-regulated pro-apoptotic genes but also compromises p53-mediated repression of ESC master transcription factors in response to DNA damage. Mechanistically, Sall4 balances p53-binding affinity between p53-activated and -repressed genes through tethering p53 to ESC enhancers. In light of our study, Sall4 may contribute to tumorigenesis by antagonizing p53-mediated apoptosis.

Highly Efficient and Chemoselective Tandem Hydroformylation-Hydrogenation of Alkenes to Alcohols over g-CN Supported Bimetallic Rh and Co Nanoparticles Catalysts.

The objective of the tandem hydroformylation-hydrogenation of alkenes to corresponding alcohols was to design an efficient and stable heterogeneous catalyst. To this end, a series of novel heterogeneous graphitic carbon nitride (g-CN) supported bimetallic Rh-Co nanoparticle catalysts (Rh-Co/g-CN) were prepared and subsequently studied for this one-pot two-step reaction. The lamellar structure makes Rh and Co nanoparticles with diameters of <1 nm and 20 nm, respectively, homogeneously deposited on the surface of g-CN layers, exhibit remarkable conversion of styrene (99.9 %) and chemoselectivity for alcohol (87.8 %). More importantly, Co nanoparticles are found to play an important role in the improvement of the chemoselectivity for alcohol due to the formation of catalytic active species [HCo(CO)y ]. Besides the detailed investigation of the catalytic properties of Rh-Co/g-CN under different reaction conditions, the reuse of Rh-Co/g-CN was conducted for five times and no evident decrease in the activity and chemoselectivity was observed. Therefore, we expect that this work could offer an initial insight into g-CN-based heterogeneous catalyst on the tandem hydroformylation-hydrogenation reaction.

CdSe/TiO2NTs Heterojunction-Based Nonenzymatic Photoelectrochemical Sensor for Glucose Detection.

Compared with a single semiconductor, the heterojunction formed by two different semiconductors usually has higher light utilization and better photoelectric performance. By using stable TiO2 nanotubes as the main subject, CdSe/TiO2NTs heterojunctions were synthesized by a hydrothermal method. XRD, TEM, SEM, PL, UV-vis, and EIS were used to characterize the fabricated CdSe/TiO2NTs. Under visible light irradiation, CdSe/TiO2NTs heterojunctions exhibited a higher absorption intensity and lower degree of photogenerated carrier recombination than TiO2. The electrons and holes were proven to be effectively separated in this heterojunction via theoretical calculation. Under CdSe/TiO2NTs' optimal conditions, the glucose concentrations (10-90 µM) had a linear relationship with the photocurrent value, and the detection limit was 3.1 µM. Moreover, the CdSe/TiO2NTs sensor exhibited good selectivity and stability. Based on the experimental data and theoretical calculations, its PEC sensing mechanism was also illuminated.

Modeling and analysis of narrow-linewidth distributed feedback lasers based on apodized laterally coupled gratings.

A physical model is demonstrated to optimize narrow-linewidth distributed feedback lasers based on apodized laterally coupled gratings (AG-DFB). The structure can effectively suppress the longitudinal spatial hole burning as well as remove the regrowth process during fabrication by using the apodized grating geometry. The studies include numerical simulations of the AG-DFB laser for its static and dynamic behaviors at different cavity lengths and facet coating conditions. The results show that the proposed device can achieve narrow linewidth, high slope efficiency, and broad modulation bandwidth, as compared to λ/4 phase-shifted DFB lasers.

Job-related stress associated with work-related upper extremity musculoskeletal disorders (UEMDs) in municipal waste collectors: the moderation and mediation effect of job support.

BACKGROUND: Since the policy of "keeping trash off of the ground" in Taiwan, long-term exposure to repetitive motion in waste collection process results in high risk of upper extremity musculoskeletal disorders (UEMDs). Thus, we assessed the moderation and mediation effects of job-related stress and job support on work-related UEMDs among municipal waste collectors. METHODS: A cross-sectional study was conducted in two cities located at northern Taiwan during 2018-2019. 626 municipal waste collectors voluntarily participated and anonymously filled out a structured questionnaire. The moderation and mediation effects of effort-reward imbalance (ERI) and social support on UEMDs were analyzed by Haye's Process Macro Model. RESULTS: Prevalence of UEMDs in municipal waste collectors were 43.4% for neck, 56.0% for shoulder, 24.1% for upper back, and 33.1% for hand/wrist. There was high prevalence of shoulder (72.2%), neck (48%), and upper back (30%) in female workers compared to male, most significantly in shoulders. In univariate and multivariate analysis, high ERI and low job support were significantly associated with ORs of 3.11 (95% CI:1.58-6.13) for elbow, 2.79 (95% CI:1.39-5.56) for shoulder, 3.39 (95% CI:1.64-7.00) for upper back and 3.83 (95% CI:1.98-7.41) for hand/wrist. Prevalent UEMDs were positively associated with high ERI in municipal waste collectors but negatively with job support. The moderation effects of ERI and job support on UEMDs, of which the measured synergy index exceeded one, were 18.24 for shoulder, 3.32 for elbow, and 2.45 for hand/wrist, but mediation effects were not significant. CONCLUSIONS: This study found municipal waste collectors with work-related upper extremity disorders were significantly associated with work-related psychological risk factors. Therefore, waste collection cannot only to be improved by semi-automatic and automatic processes but immediate intervention programs for the reduction of psychological risk factors is needed promptly.

Novel insights into aerobic duration control-based partial nitritation in source-separated blackwater treatment: Growth type, inoculation source, and comammox threat.

Aerobic duration control (ADC), whereby aeration is terminated before nitrite is extremely oxidized during the nitrification process, is an effective strategy to achieve partial nitritation (PN) for blackwater. This study evaluated the effects of microbial growth type, influent ammonia-oxidizing organisms (AOO), and comammox bacteria from seeding sludge to ADC-based PN. The long-term operation of lab-scale reactors and model simulations were implemented to select the best growth type. The biofilm formed on the inner wall of the activated sludge reactor decreased the nitrite accumulation ratio (NAR) from 99.2% to 77.2%. Meanwhile, the NAR of the pure-biofilm reactor decreased from 95.9% to 47.8%. The deteriorated PN of the biofilm-related reactors was due to the extended solid retention time and increased substrate saturation constants of AOOs compared with those of nitrite-oxidizing organisms (NOO). Periodic biofilm carrier regeneration and biofilm thickness control can recover PN performance but are difficult to implement. In contrast, the optimized activated sludge reactor exhibited high (NAR >94%) and stable (>3 months) PN performance when treating real blackwater. Nitrifiers were found in blackwater, and chemically enhanced high-rate activated sludge pretreatment removed more NOOs than AOOs (41.8% vs. 24.3%) and increased the influent AOO/NOO ratio. Interestingly, the influent AOOs supported fast PN start-up in the moving-bed biofilm reactor without the initial inoculation of activated sludge. Moreover, model simulations verified that high and stable PN could also be realized in an activated sludge reactor by the continuous inoculation of influent AOOs, which is a novel PN start-up strategy. Metagenomic analyses showed that the comammox bacteria from the seeding sludge eventually disappeared owing to their intrinsic specific growth rates and free ammonia inhibition. The findings of this study will provide insightful guidelines for PN application in decentralized and semi-centralized wastewater treatment systems.

Inverse design of the MMI power splitter by asynchronous double deep Q-learning.

The asynchronous double deep Q-learning (A-DDQN) method is proposed to design the multi-mode interference (MMI) power splitters for low insertion loss and wide bandwidth from 1200 to 1650 nm wavelength range. By using A-DDQN to guide hole etchings in the interference region of MMI, the target splitting ratio (SR) can be obtained with much less CPU time (about 10 hours for one design) and more effective utilization of the computational resources in asynchronous/parallel manner. Also, this method can simplify the design by using relatively few holes to obtain the same SR with small return loss.

Short-term non-vitamin K antagonist oral anticoagulants vs. warfarin in preventing device-related thrombosis after left atrial appendage closure.

Up to now we have had few evidences on the Non-vitamin K Antagonist Oral Anticoagulants (NOACs)' efficacy and safety in preventing device-related thrombosis (DRT) after percutaneous left atrial appendage closure (LAAC). After LAAC implantation, short-term anticoagulation (NOACs or warfarin) was prescribed. Baseline clinical characteristics, procedural parameters and postoperative follow up data were collected and compared between the two groups. From May 2014 to June 2018, 361 consecutive patients underwent LAAC implantation in our center. 170 patients received warfarin for 45 days at least after LAAC implantation, who were compared with 170 age-matched patients on NOACs. The basic clinical characteristics, as well as procedural parameters were comparable between the two groups, while the NOACs group had higher average CHA2DS2-VASc score (3.3  ±  1.6 vs. 2.9  ±  1.5, P = 0.022*). At 45 days follow up, 289 (86.5%) patients received transoesophageal echocardiography (TEE), and the overall incidence of DRT was 2.4%. The DRT rate was not significantly different between the NOACs and warfarin groups (2.7% vs. 2.1%, P > 0.05), while the NOACs group showed lower all bleeding rate (1.2% vs. 9.0%, P < 0.01). The rates of ischemic stroke as well as major bleeding were comparable between the two groups. Except for 7 DRTs and 1 major peri-device leakage (> 5 mm), anticoagulation was terminated in all other patients. During the follow-up thereafter (mean 868 days), the rates of all-cause death, ischemic stroke and bleeding were comparable between the two groups. Short-term NOACs after LAAC appear to be as effective as warfarin in preventing DRT, with lower bleeding rate.

Long noncoding RNA LINC00319 regulates ROMO1 expression and promotes bladder cancer progression via miR-4492/ROMO1 axis.

Growing reports indicate that long noncoding RNA (lncRNA) are involved in the regulation of various biological processes of cancer cells. LINC00319 is an ill investigated lncRNA and has been shown to regulate lung cancer, nasopharyngeal carcinoma and ovarian cancer. Nevertheless, its roles in bladder cancer (BCa) remain unclear. In our research, LINC00319 was shown to be an upregulated lncRNA in BCa tissues. LINC00319 expression is negatively correlated with the patient's prognosis. Silencing of LINC00319 suppressed BCa proliferation and invasiveness. In addition, the data indicated LINC00319 was a sponge for miR-4492 and miR-4492 suppressed ROMO1 expression in BCa. Furthermore, our results illustrated miR-4492/ROMO1 axis regulates proliferation, migration, and invasion and LINC00319 exerts oncogenic roles through modulating miR-4492/ROMO1 axis. In sum, this study suggested that LINC00319 acts as oncogenic roles in BCa progression.

Two CRISPR/Cas9 Systems Developed in Thermomyces dupontii and Characterization of Key Gene Functions in Thermolide Biosynthesis and Fungal Adaptation.

Thermomyces dupontii, a widely distributed thermophilic fungus, is an ideal organism for investigating the mechanism of thermophilic fungal adaptation to diverse environments. However, genetic analysis of this fungus is hindered by a lack of available and efficient gene-manipulating tools. In this study, two different Cas9 proteins from mesophilic and thermophilic bacteria, with in vivo expression of a single guide RNA (sgRNA) under the control of tRNAGly, were successfully adapted for genome editing in T. dupontii We demonstrated the feasibility of applying these two gene editing systems to edit one or two genes in T. dupontii The mesophilic CRISPR/Cas9 system displayed higher editing efficiency (50 to 86%) than the thermophilic CRISPR/Cas9 system (40 to 67%). However, the thermophilic CRISPR/Cas9 system was much less time-consuming than the mesophilic CRISPR/Cas9 system. Combining the CRISPR/Cas9 systems with homologous recombination, a constitutive promoter was precisely knocked in to activate a silent polyketide synthase-nonribosomal peptide synthase (PKS-NRPS) biosynthetic gene, leading to the production of extra metabolites that did not exist in the parental strains. Metabolic analysis of the generated biosynthetic gene mutants suggested that a key biosynthetic pathway existed for the biosynthesis of thermolides in T. dupontii, with the last two steps being different from those in the heterologous host Aspergillus Further analysis suggested that these biosynthetic genes might be involved in fungal mycelial growth, conidiation, and spore germination, as well as in fungal adaptation to osmotic, oxidative, and cell wall-perturbing agents.IMPORTANCEThermomyces represents a unique ecological taxon in fungi, but a lack of flexible genetic tools has greatly hampered the study of gene function in this taxon. The biosynthesis of potent nematicidal thermolides in T. dupontii remains largely unknown. In this study, mesophilic and thermophilic CRISPR/Cas9 gene editing systems were successfully established for both disrupting and activating genes in T. dupontii In this study, a usable thermophilic CRISPR/Cas9 gene editing system derived from bacteria was constructed in thermophilic fungi. Chemical analysis of the mutants generated by these two gene editing systems identified the key biosynthetic genes and pathway for the biosynthesis of nematocidal thermolides in T. dupontii Phenotype analysis and chemical stress experiments revealed potential roles of secondary metabolites or their biosynthetic genes in fungal development and adaption to chemical stress conditions. These two genomic editing systems will not only accelerate investigations into the biosynthetic mechanisms of unique natural products and functions of cryptic genes in T. dupontii but also offer an example for setting up CRISPR/Cas9 systems in other thermophilic fungi.

Narrow-linewidth distributed feedback moiré-grating laser for high-speed optical communications.

A time-domain traveling wave model is described to simulate a novel distributed feedback moiré-grating (DFM) laser, which can suppress the longitudinal spatial hole burning (LSHB) effect and improve the spectral linewidth for high-speed optical communications. The longitudinal photon distribution, linewidth, and dynamic modulation characteristics of the DFM lasers are calculated and compared with the state-of-the-art distributed feedback lasers. We found that the DFM laser can also improve the light-current slope efficiency and modulation bandwidth by introducing multiple $\unicode{x03C0} $π-phase shifts at the moiré envelope index changes while effectively suppressing the LSHB.

3D Hydrogen Titanate Nanotubes on Ti Foil: A Carrier for Enzymatic Glucose Biosensor.

Glucose oxidase (GOx) based biosensors are commercialized and marketed for the high selectivity of GOx. Incorporation nanomaterials with GOx can increase the sensitivity performance. In this work, an enzyme glucose biosensor based on nanotubes was fabricated. By using Ti foil as a carrier, hydrogen titanate nanotubes (HTNTs), which present fine 3D structure with vast pores, were fabricated in-situ by the hydrothermal treatment. The multilayer nanotubes are open-ended with a diameter of 10 nm. Then glucose oxidase (GOx) was loaded on the nanotubes by cross-linking to form an electrode of the amperometric glucose biosensor (GOx/HTNTs/Ti electrode). The fabricated GOx/HTNTs/Ti electrode had a linear response to 1-10 mM glucose, and the response time was 1.5 s. The sensitivity of the biosensor was 1.541 µA·mM-1·cm-2, and the detection limit (S/N = 3) was 59 µM. Obtained results indicate that the in-situ fabrication and unique 3D structure of GOx/HTNTs/Ti electrode are beneficial for its sensitivity.

LncRNA miR143HG suppresses bladder cancer development through inactivating Wnt/ß-catenin pathway by modulating miR-1275/AXIN2 axis.

Although increasing long noncoding RNAs (lncRNAs) have been identified by high-throughput sequencing, their functions in human cancer remain largely unknown. The function of lncRNA miR143HG has not been explored before. In the present study, we found that miR143HG expression was significantly downregulated in bladder cancer tissues (BCa) compared with normal tissues. We showed that miR143HG high expression was associated with a high survival rate in BCa patients. Gain-of-function assays demonstrated that miR143HG overexpression suppressed the proliferation, arrested cell cycle progression, and attenuated migration and invasion of BCa cells in vitro. In vivo assay illustrated that ectopic expression of miR143HG inhibited BCa growth in vivo. Mechanistically, miR143HG was identified to inhibit the level of miR-1275, whereas miR-1275 directly targeted AXIN2, a negative regulator of the Wnt/ß-catenin pathway. Restoration of miR-1275 or knockdown of AXIN2 significantly rescued the proliferation, migration, and invasion abilities of BCa cells. In summary, our findings demonstrated that miR143HG/miR-1275/AXIN2 axis regulates BCa development by modulating the Wnt/ß-catenin pathway.

High-power edge-emitting laser based on a parity-time-structured Bragg reflection waveguide.

A parity-time-structured Bragg reflection waveguide is proposed and analyzed for realizing a high-power laser. A single transverse mode with the optical field confined mainly in the low-index core is discussed to improve the catastrophic optical damage threshold for high output power. The designed scheme can potentially mitigate the heat buildup by moving the injection from the central narrow core to the outer large-area claddings, while suppressing the coupler mode transversely. The structure can achieve high output power with a short cavity length, low lasing threshold, and high power conversion efficiency.

Soluble ST2 for Prediction of Clinical Outcomes in Patients with ST-Segment Elevation Myocardial Infarction Receiving Primary PCI.

Soluble suppression of tumorigenicity 2 (sST2), a biomarker representing myocardial fibrosis and inflammation, has been applied in risk stratification of patients with myocardial infarction (MI). However, whether primary PCI (PPCI) will eliminate the predictive value of sST2 in STEMI patients has not been well studied. Here, we conducted a prospective clinical trial to evaluate the correlation between sST2 and prognosis in STEMI patients undergoing PPCI. sST2 levels were measured in 295 STEMI patients (60.2 ± 10.8 years) at admission using a high sensitivity assay. Baseline sST2 levels were significantly associated with heart function, biomarkers of inflammation, and myocardial injury. During a 12-month follow-up, 19 patients had major adverse cardiovascular events (MACEs). Greater sST2 was continuously associated with a higher risk of incident MACEs. Such association remained even after adjusting for other risk factors in a multivariate Cox analysis. A baseline sST2 level in the highest quartile (≥ 58.7 ng/mL) was independently associated with mortality (HR: 5.01, 95%CI: 1.02-16.30, P = 0.048). More incident heart failure was seen in the group with greater sST2, however, the association was not significant after adjustment. Therefore, baseline sST2 may be useful to predict MACEs, especially mortality, in STEMI patients receiving PPCI.

[Therapeutic effect of tadalafil on lower urinary tract symptoms with erectile dysfunction].

OBJECTIVE: To investigate the therapeutic effect of low-dose tadalafil on BPH-induced lower urinary tract symptoms (LUTS) complicated with ED. METHODS: We randomly assigned 126 patients with BPH-induced LUTS and ED to receive daily administration of tadalafil (5 mg) plus tamsulosin hydrochloride sustained-release capsules (0.2 mg) (treatment group Ⅰ ［T-Ⅰ］, n = 42), tadalafil (5 mg) only (treatment group Ⅱ ［T-Ⅱ］, n = 42) or placebo (control group, n = 42), all for 12 weeks. Before and after 6 and 12 weeks of medication, and at 4 and 8 weeks after drug withdrawal, we recorded and compared the IPSS sub-item scores in the voiding stage and urinary storage symptoms, total IPSS, IIEF-5 scores, and the frequency of sexual activities among the three groups of patients. RESULTS: As for the IPSS sub-item scores in the voiding stage symptoms, T-Ⅰ showed statistically significant differences between any two of the five time points (P < 0.05), but not T-Ⅱ between the baseline and 6-week medication or 8-week withdrawal (P > 0.05), or between 6-week medication and 8-week withdrawal (P > 0.05), nor did the control group among the five time points (P > 0.05). Statistically significant differences were observed between any two of the three groups at 12 weeks of medication and 4 weeks after drug withdrawal (P < 0.05), but not between the T-Ⅱ and control groups at 6 weeks of medication or 8 weeks after withdrawal (P > 0.05). As to the IPSS sub-item scores in the urinary storage symptoms, there were significant differences between any two time points in T-Ⅰ and T-Ⅱ (P < 0.05), but not in the control (P > 0.05), nor between T-Ⅰ and T-Ⅱ at 6 or 12 weeks of medication or at 4 or 8 weeks after drug withdrawal (P > 0.05). With regard to the total IPSS, statistically significant differences were found between any two of the three groups at 6 and 12 weeks of medication and 4 and 8 weeks after drug withdrawal (P < 0.05), but not between 6-week medication and 8-week withdrawal in T-Ⅰ or T-Ⅱ (P > 0.05), nor among the five time points in the control group (P > 0.05). Concerning the IIEF-5 scores, there was no significant difference in the frequency of sexual activities between the three groups （Ｐ>0.05）.There were statistically significant differences between any two of the three groups at 6 weeks of medication and 8 weeks after drug withdrawal (Ｐ<0.05), but not between 6-week medication and 4- or 8-week withdrawal (P > 0.05) or between 4- and 8-week withdrawal (P > 0.05) in T-Ⅰ, nor between 6-week medication and 8-week withdrawal in T-Ⅱ (P > 0.05) or among the five time points in the control (P > 0.05), nor between T-Ⅰ and T-Ⅱ at 12 weeks of medication (P > 0.05) or 4 weeks after drug withdrawal (P > 0.05). CONCLUSIONS: Daily administration of tadalafil at 5 mg can effectively improve the IPSS sub-item scores in the urinary storage symptoms and IIEF-5 scores, with a persistent effect after withdrawal similar to that of its combination with other drugs, and therefore can be recommended for the treatment of BPH-induced LUTS complicated with ED.

LncRNA THOR promotes human renal cell carcinoma cell growth.

BACKGROUND: Recent studies have characterized a novel but extremely conserved long non-coding RNA (LncRNA) THOR. THOR directly associates with insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) to promote mRNA stabilization of key pro-cancerous genes. RESULTS: Here, we show that THOR is expressed in human renal cell carcinoma (RCC) tissues and established/primary human RCC cells. It was not detected in normal renal tissues nor in HK-2 and primary human renal epithelial cells. THOR silencing (by targeted siRNAs) or CRISPR/Cas9 knockout inhibited RCC cell growth, viability and proliferation in vitro. Reversely, forced over-expression of THOR promoted RCC cell survival and proliferation. IGF2BP1-regulated genes, including IGF2, GLI1 and Myc, were downregulated by THOR silencing or knockout, but they were upregulated after THOR over-expression. In vivo, THOR-knockout 786-O tumors grew significantly slower than the control tumors in nude mice. CONCLUSION: THOR expression promotes RCC cell growth in vitro and in vivo. THOR could be a novel and important therapeutic target for human RCC.