LuxR-Type SCO6993 Negatively Regulates Antibiotic Production at the Transcriptional Stage by Binding to Promoters of Pathway-Specific Regulatory Genes in Streptomyces coelicolor.

SCO6993 (606 amino acids) in Streptomyces coelicolor belongs to the large ATP-binding regulators of the LuxR family regulators having one DNA-binding motif. Our previous findings predicted that SCO6993 may suppress the production of pigmented antibiotics, actinorhodin, and undecylprodigiosin, in S. coelicolor, resulting in the characterization of its properties at the molecular level. SCO6993-disruptant, S. coelicolor ΔSCO6993 produced excess pigments in R2YE plates as early as the third day of culture and showed 9.0-fold and 1.8-fold increased production of actinorhodin and undecylprodigiosin in R2YE broth, respectively, compared with that by the wild strain and S. coelicolor ΔSCO6993/SCO6993+. Real-time polymerase chain reaction analysis showed that the transcription of actA and actII-ORF4 in the actinorhodin biosynthetic gene cluster and that of redD and redQ in the undecylprodigiosin biosynthetic gene cluster were significantly increased by SCO6993-disruptant. Electrophoretic mobility shift assay and DNase footprinting analysis confirmed that SCO6993 protein could bind only to the promoters of pathway-specific transcriptional activator genes, actII-ORF4 and redD, and a specific palindromic sequence is essential for SCO6993 binding. Moreover, SCO6993 bound to two palindromic sequences on its promoter region. These results indicate that SCO6993 suppresses the expression of other biosynthetic genes in the cluster by repressing the transcription of actII-ORF4 and redD and consequently negatively regulating antibiotic production.

Association between FSAP 1601G>A polymorphism and venous thromboembolism risk: A meta-analysis.

OBJECTIVE: Previous several studies have shown that factor VII-activating protease (FSAP) gene 1601G>A polymorphism is related to the occurrence of venous thromboembolism, but the results are inconsistent and controversial. Therefore, we conducted a meta-analysis to explore the association between FSAP 1601G>A polymorphism and venous thromboembolism susceptibility. METHODS: We managed a systematic literature search through Pubmed, Embase, Web of Science, China National Knowledge Infrastructure, and WanFang databases to collect research data related to FSAP gene 1601G>A polymorphism and susceptibility to venous thromboembolism published before May 2019. Data analysis was performed through Revman 5.3 and Stata 12.0 software, the pooled odd ratios and 95% confidence intervals were calculated. Additionally, the sensitivity analysis and publication bias assessment were also performed. RESULTS: A total of seven case-control studies were included and evaluated, including 2411 venous thromboembolism cases and 2850 controls. The meta-analysis results revealed that the FSAP 1601G>A mutation is associated with venous thromboembolism risk, and statistically significance was observed under three genetic comparison models (A: G, odds ratio: 1.33, 95% confidence interval: 1.07-1.66; GA: GG, odds ratio: 1.34, 95% confidence interval: 1.06-1.68; and GA + AA: GG, odds ratio: 1.33, 95% confidence interval: 1.06-1.66). CONCLUSION: This study demonstrated that the FSAP 1601G>A polymorphism may be associated with venous thromboembolism susceptibility.

Efficacy of pudendal nerve block for alleviation of catheter-related bladder discomfort in male patients undergoing lower urinary tract surgeries: A randomized, controlled, double-blind trial.

BACKGROUND: Catheter-related bladder discomfort (CRBD) to an indwelling urinary catheter is defined as a painful urethral discomfort, resistant to conventional opioid therapy, decreasing the quality of postoperative recovery. According to anatomy, the branches of sacral somatic nerves form the afferent nerves of the urethra and bladder triangle, which deriving from the ventral rami of the second to fourth sacral spinal nerves, innervating the urethral muscles and sphincter of the perineum and pelvic floor; as well as providing sensation to the penis and clitoris in males and females, which including the urethra and bladder triangle. Based on this theoretical knowledge, we formed a hypothesis that CRBD could be prevented by pudendal nerve block. OBJECTIVE: To evaluate if bilateral nerve stimulator-guided pudendal nerve block could relieve CRBD through urethra discomfort alleviation. DESIGN AND SETTING: Single-center randomized parallel controlled, double blind trial conducted at West China Hospital, Sichuan University, China. PARTICIPANTS: One hundred and eighty 2 male adult patients under general anesthesia undergoing elective trans-urethral resection of prostate (TURP) or trans-urethral resection of bladder tumor (TURBT). Around 4 out of 182 were excluded, 178 patients were randomly allocated into pudendal and control groups, using computer-generated randomized numbers in a sealed envelope method. A total of 175 patients completed the study. INTERVENTION: Pudendal group received general anesthesia along with nerve-stimulator-guided bilateral pudendal nerve block and control group received general anesthesia only. MAIN OUTCOME MEASURES: Incidence and severity of CRBD; and postoperative VAS score of pain. RESULTS: CRBD incidences were significantly lower in pudendal group at 30 minutes (63% vs 82%, P = .004), 2 hours (64% vs 90%, P < .000), 8 hours (58% vs 79%, P = .003) and 12 hours (52% vs 69%, P = .028) also significantly lower incidence of moderate to severe CRBD in pudendal group at 30 minutes (29% vs 57%, P < .001), 2 hours (22% vs 55%, P < .000), 8 hours (8% vs 27%, P = .001) and 12 hours (6% vs 16%, P = .035) postoperatively. The postoperative pain score in pudendal group was lower at 30 minutes (P = .003), 2 hours (P < .001), 8 hours (P < .001), and 12 hours (P < .001), with lower heart rate and mean blood pressure. One patient complained about weakness in levator ani muscle. CONCLUSION: General anesthesia along with bilateral pudendal nerve block decreased the incidence and severity of CRBD for the first 12 hours postoperatively.

Intensity-modulated proton therapy reduces the dose to normal tissue compared with intensity-modulated radiation therapy or passive scattering proton therapy and enables individualized radical radiotherapy for extensive stage IIIB non-small-cell lung cancer: a virtual clinical study.

PURPOSE: To compare dose volume histograms of intensity-modulated proton therapy (IMPT) with those of intensity-modulated radiation therapy (IMRT) and passive scattering proton therapy (PSPT) for the treatment of stage IIIB non-small-cell lung cancer (NSCLC) and to explore the possibility of individualized radical radiotherapy. METHODS AND MATERIALS: Dose volume histograms designed to deliver IMRT at 60 to 63 Gy, PSPT at 74 Gy, and IMPT at the same doses were compared and the use of individualized radical radiotherapy was assessed in patients with extensive stage IIIB NSCLC (n = 10 patients for each approach). These patients were selected based on their extensive disease and were considered to have no or borderline tolerance to IMRT at 60 to 63 Gy, based on the dose to normal tissue volume constraints (lung volume receiving 20 Gy [V20] of <35%, total mean lung dose <20 Gy; spinal cord dose, <45 Gy). The possibility of increasing the total tumor dose with IMPT for each patient without exceeding the dose volume constraints (maximum tolerated dose [MTD]) was also investigated. RESULTS: Compared with IMRT, IMPT spared more lung, heart, spinal cord, and esophagus, even with dose escalation from 63 Gy to 83.5 Gy, with a mean MTD of 74 Gy. Compared with PSPT, IMPT allowed further dose escalation from 74 Gy to a mean MTD of 84.4 Gy (range, 79.4-88.4 Gy) while all parameters of normal tissue sparing were kept at lower or similar levels. In addition, IMPT prevented lower-dose target coverage in patients with complicated tumor anatomies. CONCLUSIONS: IMPT reduces the dose to normal tissue and allows individualized radical radiotherapy for extensive stage IIIB NSCLC.

Controlled release of dual drugs from emulsion electrospun nanofibrous mats.

The purpose of this work is to develop a novel type of tissue engineering scaffold or drugs delivery carrier with the capability of encapsulation and controlled release drugs. In this study, Rhodamine B and Bovine Serum Albumin (BSA) were successfully incorporated into nanofibers by means of emulsion electrospinning. The morphology of composite nanofibers was studied by Scanning Electron Microscopy (SEM). The composite nanofibrous mats made from emulsion electrospinning were characterized by water contact angle measurement and X-ray diffraction. In vitro dual drugs release behaviors from composite nanofibrous mats were investigated. The results indicated that the incorporated drug and/or proteins in composite fibrous mats made from electrospinning could be control released by adjusting the processes of emulsions preparation.