Analysis of Energy Loss Characteristics of Vertical Axial Flow Pump Based on Entropy Production Method under Partial Conditions.

The energy loss of the vertical axial flow pump device increases due to the unstable internal flow, which reduces the efficiency of the pump device and increases its energy consumption of the pump device. The research results of the flow loss characteristics of the total internal conduit are still unclear. Therefore, to show the internal energy loss mechanism of the axial flow pump, this paper used the entropy production method to calculate the energy loss of the total conduit of the pump device to clarify the internal energy loss mechanism of the pump device. The results show that the energy loss of the impeller is the largest under various flow conditions, accounting for more than 40% of the total energy loss of the pump device. The variation trend of the volume average entropy production and the energy loss is similar under various flow coefficients (KQ). The volume average entropy production rate (EPR) and the energy loss decrease first and then increase with the increase of flow, the minimum volume average entropy production is 378,000 W/m3 at KQ = 0.52, and the area average EPR of the impeller increases gradually with the increase of flow. Under various flow coefficient KQ, the energy loss of campaniform inlet conduit is the smallest, accounting for less than 1% of the total energy loss. Its maximum value is 63.58 W. The energy loss of the guide vane and elbow increases with the increase of flow coefficient KQ, and the maximum ratio of energy loss to the total energy loss of the pump device is 29% and 21%, respectively, at small flow condition KQ = 0.38. The energy loss of straight outlet conduit reduces first and then increases with the increase of flow coefficient KQ. When flow coefficient KQ = 0.62, it accounts for 27% of the total energy loss of the pump device, but its area average entropy production rate (EPR) and volume average entropy production rate (EPR) are small. The main entropy production loss in the pump device is dominated by entropy production by turbulent dissipation (EPTD), and the proportion of entropy production by direct dissipation (EPDD) is the smallest.

Clinical Efficacy of PD-1 Inhibitors Plus Split-Course Radiotherapy in the First-Line Treatment of Advanced Kidney Cancer: A Randomized Controlled Trial.

Objective: To assess the clinical efficacy of programmed death 1 (PD-1) inhibitors plus split-course radiotherapy in the first-line treatment of advanced kidney cancer. Methods: In this prospective, randomized, single-blinded, controlled trial, 44 patients with advanced kidney cancer initially treated in our hospital from January 2017 to December 2018 were recruited. They were concurrently and randomly assigned at a ratio of 1 : 1 to the control group and the study group, with 22 cases in each group. The control group received PD-1 inhibitor nivolumab combined with ipilimumab, and the study group received split-course radiotherapy plus. The primary endpoint is clinical efficacy, and the secondary endpoints are progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Results: Nivolumab plus split-course radiotherapy was associated with an objective remission rate (ORR) of 59.09% versus nivolumab alone with an ORR of 27.27%. The median PFS was 21.5 months (95% CI: 14.1-NA) after single nivolumab therapy and 28.1 months (95% CI: 24.5-NA) after nivolumab plus split-course radiotherapy, with an HR of 1.875 (95% CI: 0.877-4.011). The median OS was 27.1 months (95% CI: 20.7-NA) after single nivolumab therapy and not reached after nivolumab plus split-course radiotherapy and an HR of 2.56 (95% CI: 1.081-6.06). Nivolumab was associated with significantly better OS plus split-course radiotherapy versus nivolumab alone. Conclusion: Nivolumab plus split-course radiotherapy in patients with advanced renal cell carcinoma significantly improves ORR and prolongs overall survival with a good safety profile.

Effects of Docetaxel plus Degarelix on Quality of Life and Vascular Endothelial Growth Factor in Patients with Prostate Cancer.

Objective: To investigate the effects of docetaxel plus degarelix on quality of life and vascular endothelial growth factor in patients with prostate cancer. Methods: Between 2018 and 2020, 38 patients with castration-resistant prostate cancer (CRPC) treated in our institution were assessed for eligibility and recruited. They were assigned at a ratio of 1 : 1 to receive either docetaxel plus degarelix (observation group) or degarelix (control group). Outcome measures included treatment efficacy, inflammatory factors level, vascular endothelial growth factor (VEGF) level, and quality of life of patients. Results: Docetaxel plus degarelix was associated with a significantly higher treatment efficacy (94.74%, including 9 (47.37%) cases of complete response (CR), 6 (31.58%) cases of partial response (PR), 4 (21.05%) cases of stable disease (SD), and 1 (5.36%) case of progressive disease (PD)) versus degarelix alone (63.16%, including 4 (21.05%) cases of CR, 5 (26.32%) cases of PR, 3 (15.79%) cases of SD, and 7 (36.84%) cases of PD) (P < 0.05). Before treatment, the two groups showed comparable levels of C-reaction protein (CRP), interleukin- (IL-) 6, and IL-10 (P > 0.05). Docetaxel plus degarelix resulted in significantly reduced levels of CRP and IL-6 and a significantly higher IL-10 level (28.84 ± 5.42, 25.31 ± 5.74, and 53.32 ± 11.02) versus degarelix alone (35.17 ± 6.31, 31.54 ± 8.17, and 42.76 ± 11.25) (P < 0.05). There were no significant differences in the urinary function, intestinal function, and hormone function scores between the two groups before treatment (P > 0.05). The patients receiving docetaxel plus degarelix had higher urinary function, intestinal function, and hormone function scores (38.87 ± 4.46, 86.51 ± 8.14, and 76.65 ± 7.15) versus monotherapy of degarelix (29.84 ± 3.58, 78.51 ± 7.31, and 66.78 ± 6.56) (P < 0.05). The two groups had similar pretreatment VEGF levels (P > 0.05). Docetaxel plus degarelix resulted in significantly lower VEGF levels (119.17 ± 21.38) versus degarelix (124.36 ± 23.14) at 6 months after treatment (P < 0.05). Conclusion: Docetaxel plus degarelix can enhance the therapeutic efficacy of patients with prostate cancer, mitigate inflammatory response, inhibit the VEGF expression of cancer cells, and improve the patients' quality of life. Further clinical trials are, however, required prior to general use in clinical practice.

Breviscapine Participates in the Progression of Prostate Cancer by Inhibiting ZFP91 Expression through Upregulation of MicroRNA-129-5p.

OBJECTIVE: To investigate the effect of breviscapine (BVP) on the development of prostate cancer and its molecular mechanism. MATERIALS AND METHODS: After treatment with breviscapine and microRNA-129-5p, MTT (3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) and cell counting kit-8 (CCK-8) tests were performed to examine the proliferation rate of cells, while Transwell was used to analyze cell migration ability; at the same time, quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the expression of microRNA-129-5p and ZFP91 in prostate cancer cells. In addition, the binding of microRNA-129-5p and ZFP91 was confirmed by dual-luciferase reporting assay; meanwhile, cell reverse experiment verified that breviscapine can regulate ZFP91 via upregulating microRNA-129-5p. RESULTS: The results of MTT, CCK-8, and Transwell experiments demonstrated that breviscapine inhibited the proliferation as well as the migration capacities of PC cells; meanwhile, it upregulated the level of microRNA-129-5p in PC cells while downregulated that of ZFP91. Furthermore, dual-luciferase reporter gene assay verified that ZFP91 was a potential target of microRNA-129-5p. Finally, cell reverse experiment confirmed that breviscapine downregulated ZFP91 expression by upregulating microRNA-129-5p, while downregulation of microRNA-129-5p partially reversed the inhibitory effect of breviscapine on cell proliferation ability. CONCLUSIONS: Breviscapine may inhibit the expression of ZFP91 through upregulating microRNA-129-5p and thus participating in the progression of PC.

Clinical Studies on the Treatment of Novel Coronavirus Pneumonia With Traditional Chinese Medicine-A Literature Analysis.

OBJECTIVE: This study aims to analyze the current situation and characteristics of traditional Chinese medicine for treatment of novel coronavirus pneumonia, clarify its clinical advantages and provide a reference for clinical treatment. METHODS: Clinical randomized controlled trials, clinical control trials and case series research involving the use of Chinese medicine for novel coronavirus pneumonia treatment were selected from PubMed, Chinese Journal Service Platform of CNKI, VIP, and WanFang Data Knowledge Service Platform from the establishment of the library to 11:00 am on April 15, 2020. The published information, research design, intervention measures and research observation index were statistically analyzed. RESULTS: Twenty studies were included. The research methods were mainly clinical controlled trials. The observation indicators were mostly fever improvement time, cough improvement time, shortness of breath improvement time, chest CT and CRP examination. Maxing Ganshi (Ephedrae Herba, Armeniacae Semen Amarum, Glycyrrhizae Radix Et Rhizoma, and Gypsum Fibrosum) decoction was the core prescription. The most frequently used drugs were Glycyrrhizae Radix Et Rhizoma (Gancao), Ephedrae Herba (Mahuang), Armeniacae Semen Amarum (Kuxingren), Atractylodis Rhizoma (Cangzhu), and Scutellariae Radix (Huangqin). The most frequently used drug combination was Ephedrae Herba (Mahuang)-Armeniacae Semen Amarum (Kuxingren). The most frequently used Chinese patent medicine was Lianhua Qingwen capsule/granule. CONCLUSIONS: Traditional Chinese medicine has widely used for novel coronavirus pneumonia in China. It is worthy of global attention. Also, high-quality randomized controlled clinical trials on the effectiveness and safety of traditional Chinese medicine in the treatment of novel coronavirus pneumonia need to carry out.

Engineering Saccharomyces cerevisiae for high yield production of α-amyrin via synergistic remodeling of α-amyrin synthase and expanding the storage pool.

α-Amyrin is a plant-originated high-valued triterpene that is highly effective against several pathological ailments. α-Amyrin production by engineered Saccharomyces cerevisiae has been achieved by introducing α-amyrin synthase (αAS). However, the low yield of α-amyrin highly limits its industrial application; the low catalytic activity of αAS and the toxic effect of α-amyrin have been considered key elements. In this study, the highest yield of α-amyrin was obtained in engineered S. cerevisiae by remodeling α-amyrin synthase MdOSC1 and expanding the storage pool. The yield of α-amyrin was increased to 11-fold higher than that of the control by the triple mutant MdOSC1N11T/P250H/P373A obtained based on the modeling analysis. Furthermore, key genes of MVA pathway were overexpressed to provide sufficient precursors, and DGA1 (Diacylglycerol acyltransferase) was overexpressed to expand the intracellular storage capacity. Finally, the as-constructed aAM12 strain produced 213.7 ± 12.4 mg/L α-amyrin in the shake flask and 1107.9 ± 76.8 mg/L in fed-batch fermentation; the fermentation yield was 106-fold higher than that of the original aAM1 strain under the same conditions, representing the highest α-amyrin yield in yeast reported to date. Microbial production of α-amyrin with over 1 g/L will be suitable for commercialization and can accelerate the industrial production of α-amyrin in yeast.

A Novel Approach for Repairing Superior Mesenteric Artery Injury During Left Nephrectomy-6-year Follow-up.

OBJECTIVE: To describe a novel approach for reconstructing the superior mesenteric artery (SMA) during left nephrectomy and review the literature. MATERIALS AND METHODS: The patient was a 57-year-old man with left back pain from an unknown cause for more than 3 hours. A computed tomography scan showed a 12- × 15-cm firm mass and a subcapsular hematoma in the left kidney. It was considered to be bleeding and rupture of the solid renal mass, and because of persistent pain and no documented distant metastatic disease, a transperitoneal laparoscopic nephrectomy was elected, but the procedure was converted to open surgery for SMA injury. We reconstructed the SMA with end-to-end anastomosis between the SMA and the left renal artery stump. RESULTS: At the 6-year follow-up, the patient had no intestine-related sequelae. CONCLUSION: Our novel approach of an end-to-end anastomosis between the SMA and the left renal artery stump is an option for SMA injury, especially when orthotopic anastomosis or repair of the SMA is not indicated.

Productive Amyrin Synthases for Efficient α-Amyrin Synthesis in Engineered Saccharomyces cerevisiae.

α-Amyrin is a plant-derived pentacyclic triterpenoid, with a lot of important physiological and pharmacological activities. The formation of α-amyrin from (3 S)-2,3-oxidosqualene is catalyzed by α-amyrin synthase (α-AS), a member of the oxidosqualene cyclase (OSC) protein family. However, α-amyrin is not yet commercially developed due to its extremely low productivity in plants. The engineered Saccharomyces cerevisiae with efficient α-amyrin production pathway could be used as an alternative and sustainable solution to produce α-amyrin from renewable raw materials. To efficiently improve α-amyrin production in S. cerevisiae, we identified two α-ASs, EjAS and MdOSC1 from Eriobotrya japonica and Malus × domestica, respectively, through strict bioinformatics screening criteria and phylogenetic analysis. The specific activities of purified EjAS and MdOSC1 were 0.0032 and 0.0293 µmol/min/mg, respectively. EjAS produced α-amyrin and ß-amyrin at a ratio of 17:3, MdOSC1 produced α-amyrin, ß-amyrin and lupeol at a ratio of 86:13:1, indicating MdOSC1 had significantly higher specific activity and higher ratio of α-amyrin than EjAS. Furthermore, MdOSC1 was introduced into S. cerevisiae combining with the increased supply of (3 S)-2,3-oxidosqualene to achieve the encouraging α-amyrin production, and the titer of α-amyrin achieved 11.97 ± 0.61 mg/L, 5.8 folds of the maximum production reported.

YAP1 regulates prostate cancer stem cell-like characteristics to promote castration resistant growth.

Castration resistant prostate cancer (CRPC) is a stage of relapse that arises after various forms of androgen ablation therapy (ADT) and causes significant morbidity and mortality. However, the mechanism underlying progression to CRPC remains poorly understood. Here, we report that YAP1, which is negatively regulated by AR, influences prostate cancer (PCa) cell self-renewal and CRPC development. Specifically, we found that AR directly regulates the methylation of YAP1 gene promoter via the formation of a complex with Polycomb group protein EZH2 and DNMT3a. In normal conditions, AR recruits EZH2 and DNMT3a to YAP1 promoter, thereby promoting DNA methylation and the repression of YAP1 gene transcription. Following ADT treatment or when AR activity is antagonized by Bicalutamide or Enzalutamide, YAP1 gene expression is switched on. In turn, YAP1 promotes SOX2 and Nanog expression and the de-differentiation of PCa cells to stem/progenitor-like cells (PCSC), which potentially contribute to disease recurrence. Finally, the knock down of YAP1 expression or the inhibition of YAP1 function by Verteporfin in TRAMP prostate cancer mice significantly suppresses tumor recurrence following castration. In conclusion, our data reveals that AR suppresses YAP1 gene expression through a novel epigenetic mechanism, which is critical for PCa cells self-renewal and the development of CRPC.

Complete mitochondrial genome of the sooty mangabey, Cercocebus atys atys (Mammalia: Primates: Cercopithecidae).

The sooty mangabey (Cercocebus atys atys) is an Old World monkey belonging to family Cercopithecidae. It has recently been widely used as an important animal model for researches related to human immunodeficiency virus (HIV) and AIDS. In this study, the mitochondrial genome sequence of this species is determined and described for the first time. It is 16,536 bp in length and consists of 13 protein-coding genes, 22 tRNA genes, 2 ribosomal RNA genes and 1 putative control region (CR). The genome organization, nucleotide composition and codon usage are similar to those reported from other monkey mitochondrial genomes. The descending order of the base composition on heavy strand is 32.5% A, 29.5% C, 25.8% T, and 12.2% G, with a relatively lower level of G and a slightly A+T bias of 58.3%. All genes are distributed on the H-strand except for the ND6 subunit gene and seven tRNA genes, which are encoded on the L-strand. This mitochondrial genome data are potentially important for the study of molecular evolution, conservation genetics and disease infection in C. a. atys.

The complete mitochondrial genome of western Mediterranean mouse, Mus spretus (Rodentia: Muridae).

The western Mediterranean mouse (Mus spretus) is a wide-spread and well-studied small mammal species in Europe. In this study, we report the complete mitochondrial genome sequence of this species for the first time. Data analysis shows that this mitogenome is entirely 16,286 bp in length and has a conservative genomic organization and gene order as most other mice. The overall nucleotide base composition is 34.1% of A, 28.6% of T, 24.6% C, and 12.7% G, with a strong A + T bias of 62.7%. All the genes are encoded on H-strand, except for the ND6 subunit gene and 8 tRNA genes, which are distributed on the L-strand. Totally 13 protein-coding genes initiate with ATN/GTG start codon and terminate with the typical stop codon (TAA/TAG) or a single T (T- -). Most of the transfer RNA genes could fold into the typical clover-leaf structure except for tRNA(Leu) and tRNA(Ser), whose dihydrouridine (DHU) arm are lost. The complete mitochondrial genome sequence reported here will be useful for population genetic and phylogenetic studies in mice.