HuR promotes castration-resistant prostate cancer progression by altering ERK5 activation via posttranscriptional regulation of BCAT1.

BACKGROUND: Castration-resistant prostate cancer (CRPC) is refractory to hormone treatment, and the underlying mechanism has not been fully elucidated. This study aimed to clarify the role and mechanism of Human antigen R (HuR) as a therapeutic target for CRPC progression. METHODS: HuR was knocked out by Cas9 or inhibited by the HuR-specific inhibitor KH-3 in CRPC cell lines and in a mouse xenograft model. The effects of HuR inhibition on tumour cell behaviors and signal transduction were examined by proliferation, transwell, and tumour xenograft assays. Posttranscriptional regulation of BCAT1 by HuR was determined by half-life and RIP assays. RESULTS: HuR knockout attenuated the proliferation, migration, and invasion of PC3 and DU145 cells in vitro and inhibited tumour progression in vivo. Moreover, BCAT1 was a direct target gene of HuR and mediated the oncogenic effect of HuR on CRPC. Mechanistically, HuR directly interacted with BCAT1 mRNA and upregulated BCAT1 expression by increasing the stability and translation of BCAT1, which activated ERK5 signalling. Additionally, the HuR-specific inhibitor KH-3 attenuated CRPC progression by disrupting the HuR-BCAT1 interaction. CONCLUSIONS: We confirmed that the HuR/BCAT1 axis plays a crucial role in CRPC progression and suggest that inhibiting the HuR/BCAT1 axis is a promising therapeutic approach for suppressing CRPC progression.

Epithelial cells derived exosomal miR-203a-3p facilitates stromal inflammation of type IIIA chronic prostatitis/chronic pelvic pain syndrome by targeting DUSP5 and increasing MCP-1 generation.

Increased proinflammatory cytokines and infiltration of inflammatory cells in the stroma are important pathological features of type IIIA chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS-A), and the interaction between stromal cells and other cells in the inflammatory microenvironment is closely related to the inflammatory process of CP/CPPS-A. However, the interaction between stromal and epithelial cells remains unclear. In this study, inflammatory prostate epithelial cells (PECs) released miR-203a-3p-rich exosomes and facilitated prostate stromal cells (PSCs) inflammation by upregulating MCP-1 expression. Mechanistically, DUSP5 was identified as a novel target gene of miR-203a-3p and regulated PSCs inflammation through the ERK1/2/MCP-1 signaling pathway. Meanwhile, the effect of exosomes derived from prostatic fluids of CP/CPPS-A patients was consistent with that of exosomes derived from inflammatory PECs. Importantly, we demonstrated that miR-203a-3p antagomirs-loaded exosomes derived from PECs targeted the prostate and alleviated prostatitis by inhibiting the DUSP5-ERK1/2 pathway. Collectively, our findings provide new insights into underlying the interaction between PECs and PSCs in CP/CPPS-A, providing a promising therapeutic strategy for CP/CPPS-A.

Effects of carbamazepine on BDNF expression in trigeminal ganglia and serum in rats with trigeminal neuralgia. / å¡é©¬è¥¿å¹³å¯¹ä¸‰å‰ç¥žç»ç—›å¤§é¼ ä¸‰å‰ç¥žç»èŠ‚åŠè¡€æ¸ ä¸­BDNF表达变化的影响.

OBJECTIVES: Trigeminal neuralgia (TN) is a severe chronic neuropathic pain that mainly affects the distribution area of the trigeminal nerve with limited treating efficacy. There are numerous treatments for TN, but currently the main clinical approach is to suppress pain by carbamazepine (CBZ). Brain-derived neurotrophic factor (BDNF) is closely related to chronic pain. This study aims to determine the effects of CBZ treatment on BDNF expression in both the trigeminal ganglion (TG) and serum of TN via a chronic constriction injury of the infraorbital nerve (ION-CCI) rat model. METHODS: The ION-CCI models were established in male Sprague-Dawley rats and were randomly divided into a sham group, a TN group, a TN+low-dose CBZ treatment group (TN+20 mg/kg CBZ group), a TN+medium-dose CBZ treatment group (TN+40 mg/kg CBZ group), and a TN+high-dose CBZ treatment group (TN+80 mg/kg CBZ group). The mechanical pain threshold in each group of rats was measured regularly before and after surgery. The expressions of BDNF and tyrosine kinase receptor B (TrkB) mRNA in TGs of rats in different groups were determined by real-time PCR, and the expression of BDNF protein on neurons in TGs was observed by immunofluorescence. Western Blotting was used to detect the protein expression of BDNF, TrkB, extracellular regulated protein kinases (ERK), and phospho-extracellular regulated protein kinases (p-ERK) in TGs of rats in different groups. The expression of BDNF in the serum of rats in different groups was detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: The results of mechanical pain sensitivity showed that there was no significant difference in the mechanical pain threshold in the right facial sensory area of the experimental rats in each group before surgery (all P>0.05). From the 3rd day after operation, the mechanical pain threshold of rats in the TN group was significantly lower than that in the sham group (all P<0.01), and the mechanical pain threshold of rats in the TN+80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 CBZ mg/kg group was higher than that in the TN group (all P<0.05). The BDNF and TrkB mRNA and protein expressions in TGs of rats in the TN group were higher than those in the sham group (all P<0.05), and those in the TN+80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 mg/kg CBZ group were lower than the TN group (all P<0.05). The p-ERK levels in TG of rats in the TN+80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 mg/kg CBZ group were significantly decreased compared with the TN group (all P<0.05). The BDNF and neuron-specific nuclear protein (NeuN) were mainly co-expressed in neuron of TGs in the TN group and they were significantly higher than those in the sham group (all P<0.05). The co-labeled expressions of BDNF and NeuN in TGs of the TN+ 80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 mg/kg CBZ group were lower than those in the TN group (all P<0.05). The results of ELISA showed that the level of BDNF in the serum of the TN group was significantly higher than that in the sham group (P<0.05). The levels of BDNF in the TN+80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 mg/kg CBZ group were lower than those in the TN group (all P<0.05). Spearman correlation analysis showed that the BDNF level in serum was negatively correlated with mechanical pain threshold (r=-0.650, P<0.01). CONCLUSIONS: CBZ treatment can inhibit the expression of BDNF and TrkB in the TGs of TN rats, reduce the level of BDNF in serum of TN rats and the phosphorylation of ERK signaling pathway, so as to inhibit TN. The serum level of BDNF can be considered as an indicator for the diagnosis and prognosis of TN.

BnaCRCs with domestication preference positively correlate with the seed-setting rate of canola.

Canola (Brassica napus) is an important oil crop worldwide. The seed-setting rate (SS) is a critical factor in determining its yield, and the development of pistils affects pollination and seed sets. However, research on seed-setting defects has been limited owing to difficulties in the identification of phenotypes, mutations, and complex genetic mechanisms. In this study, we found a stigma defect (sd) mutant in B. napus, which had no nectary. The SS of sd mutants in the field was approximately 93.4% lower than that of the wild type. Scanning and transmission electron microscopy imaging of sd mutants showed a low density of stigma papillary cells and stigma papillary cell vacuoles that disappeared 16 h after flowering. Genetic analysis of segregated populations showed that two recessive nuclear genes are responsible for the mutant phenotype of sd. Based on re-sequencing and map-based cloning, we reduced the candidate sites on ChrA07 (BnaSSA07) and ChrC06 (BnaSSC06) to 30 and 67 kb, including six and eight predicted genes, respectively. Gene analyses showed that a pair of CRABS CLAW (CRC) homeologous genes at BnaSSA07 and BnaSSC06 were associated with the development of carpel and nectary. BnaSSA07.CRC and BnaSSC06.CRC candidate genes were found to be expressed in flower organs only, with significant differences in their expression in the pistils of the near-isogenic lines. DNA sequencing showed transposon insertions in the upstream region and intron of the candidate gene BnaSSA07.crc. We also found that BnaSSC06.crc exists widely in the natural population and we give possible reasons for its widespread existence.

Spatial heterogeneity of tumor microenvironment influences the prognosis of clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is an immunologically and histologically diverse tumor. However, how the structural heterogeneity of tumor microenvironment (TME) affects cancer progression and treatment response remains unclear. Hence, we characterized the TME architectures of ccRCC tissues using imaging mass cytometry (IMC) and explored their associations with clinical outcome and therapeutic response. METHODS: Using IMC, we profiled the TME landscape of ccRCC and paracancerous tissue by measuring 17 markers involved in tissue architecture, immune cell and immune activation. In the ccRCC tissue, we identified distinct immune architectures of ccRCC tissue based on the mix score and performed cellular neighborhood (CN) analysis to subdivide TME phenotypes. Moreover, we assessed the relationship between the different TME phenotypes and ccRCC patient survival, clinical features and treatment response. RESULTS: We found that ccRCC tissues had higher levels of CD8+ T cells, CD163- macrophages, Treg cells, endothelial cells, and fibroblasts than paracancerous tissues. Immune infiltrates in ccRCC tissues distinctly showed clustered and scattered patterns. Within the clustered pattern, we identified two subtypes with different clinical outcomes based on CN analysis. The TLS-like phenotype had cell communities resembling tertiary lymphoid structures, characterized by cell-cell interactions of CD8+ T cells-B cells and GZMB+CD8+ T cells-B cells, which exhibited anti-tumor features and favorable outcomes, while the Macrophage/T-clustered phenotype with macrophage- or T cell-dominated cell communities had a poor prognosis. Patients with scattered immune architecture could be further divided into scattered-CN-hot and scattered-CN-cold phenotypes based on the presence or absence of immune CNs, but both had a better prognosis than the macrophage/T-clustered phenotype. We further analyzed the relationship between the TME phenotypes and treatment response in five metastatic ccRCC patients treated with sunitinib, and found that all three responders were scattered-CN-hot phenotype while both non-responders were macrophage/T-clustered phenotype. CONCLUSION: Our study revealed the structural heterogeneity of TME in ccRCC and its impact on clinical outcome and personalized treatment. These findings highlight the potential of IMC and CN analysis for characterizing TME structural units in cancer research.

Long non-coding RNA MSTRG.81401 short hairpin RNA relieves diabetic neuropathic pain and behaviors of depression by inhibiting P2X4 receptor expression in type 2 diabetic rats.

Patients with diabetic neuropathic pain (DNP) experience immense physical and mental suffering, which is comorbid with other mental disorders, including major depressive disorder (MDD). P2X4 receptor, one of the purinergic receptors, is a significant mediator of DNP and MDD. The present study aimed to identify the roles and mechanisms of MSTRG.81401, a long non-coding RNA (lncRNA), in alleviating DNP and MDD-like behaviors in type 2 diabetic rats. After administration with MSTRG.81401 short hairpin RNA (shRNA), the model + MSTRG.81401 shRNA group demonstrated increased mechanical withdrawal threshold, thermal withdrawal latency, open-field test, and sucrose preference test; however, immobility time on the forced swimming test decreased. MSTRG.81401 shRNA administration significantly decreased the expression of the P2X4 receptor, tumor necrosis factor-α, and interleukin-1ß in the hippocampus and spinal cord in the model + MSTRG.81401 shRNA group. Simultaneously, MSTRG.81401 shRNA administration downregulated phosphorylation of ERK1/2 in the hippocampus and spinal cord. Thus, lncRNA MSTRG.81401 shRNA can alleviate DNP and MDD-like behaviors in type 2 diabetic rats and may downregulate the expression of P2X4 receptors in the hippocampus and spinal cord of rats.

Glucocorticoid nanoformulations relieve chronic pelvic pain syndrome and may alleviate depression in mice.

BACKGROUND: Chronic pelvic pain syndrome (CPPS) is a typical symptom of chronic prostatitis (CP) in males that may cause abnormal urination, sexual dysfunction, or depression and significantly affect the quality of life of the patient. Currently, there is no effective treatment for CPPS due to its recurrence and intractability. For synergistic CPPS therapy, we developed pH/reactive oxygen species (ROS) dual-responsive dexamethasone (Dex) nanoformulations using a ROS-responsive moiety and phytochemical modified α-cyclodextrin (α-CD) as the carrier. RESULTS: Dex release from the nanoformulations can be controlled in acidic and/or ROS-rich microenvironments. The fabricated Dex nanoformulations can also be efficiently internalized by lipopolysaccharide (LPS)-stimulated macrophages, prostatic epithelial cells, and stromal cells. Moreover, the levels of proinflammatory factors (e.g., TNF-α, IL-1ß, and IL-17 A) in these cells were significantly decreased by Dex nanoformulations treatment through the release of Dex, phytochemical and elimination of ROS. In vivo experiments demonstrated notable accumulation of the Dex nanoformulations in prostate tissue to alleviate the symptoms of CPPS through the downregulation of proinflammatory factors. Interestingly, depression in mice may be relieved due to alleviation of their pelvic pain. CONCLUSION: We fabricated Dex nanoformulations for the effective management of CPPS and alleviation of depression in mice.

A New Strategy for Highly Efficient Separation between Monovalent Cations by Applying Opposite-Oriented Pressure and Electric Fields.

Biological ion channels exhibit excellent ion selectivity, but it has been challenging to design their artificial counterparts, especially for highly efficient separation of similar ions. Here, a new strategy to achieve high selectivity between alkali metal ions with artificial nanostructures is reported. Molecular dynamics (MD) simulations and experiments are combined to study the transportation of monovalent cations through graphene oxide (GO) nanoslits by applying pressure or/and electric fields. It is found that the ionic transport selectivity under the pressure driving reverses compared with that under the electric field driving. Moreover, MD simulations show that different monovalent cations can be separated with unprecedentedly high selectivity by applying opposite-oriented pressure and electric fields. This highly efficient separation originates from two distinctive ionic transporting modes, that is, hydration shells drive ions under pressure, but drag ions under the electric field. Hence, ions with different hydration strengths can be efficiently separated by tuning the net mobility induced by the two types of driving forces when the selected ions are kept moving while the other ones are immobilized. And nanoconfinement is confirmed to enhance the separation efficacy. This discovery paves a new avenue for separating similar ions without elaborately designing biomimetic nanostructures.

Photoselective sharp enucleation of the prostate with a front-firing 532-nm laser versus photoselective vaporization of the prostate in the treatment of benign prostatic hyperplasia: a randomised controlled trial with 1-year followup results.

BACKGROUND: We designed a new surgical procedure to treat benign prostatic hyperplasia(BPH). In order to verify its effectiveness and safety, we constructed this randomized controlled trial to compare the efficacy of our innovative enucleation technique- photoselective sharp enucleation of the prostate (PSEP), with a front-firing 532-nm laser and the traditional technique-photoselective vaporization of the prostate (PVP) in the treatment of BPH. METHODS: A total of 154 consecutive patients diagnosed with bladder outlet obstruction secondary to BPH in our center from June 2018 to April 2019 were randomly divided into the PSEP group (n = 77) and the PVP group (n = 77) and were treated surgically with either PSEP or PVP. All patients were assessed preoperatively and followed up at 1, 6, and 12 months postoperatively. The international prostate symptom score,quality-of-life score, postvoid residual urine volume, maximum urine flow rate, prostate volume, prostate-specific antigen, and adverse events were compared. RESULTS: The lower urinary tract symptoms in both groups were significantly improved compared with the baseline at 1, 6, and 12 months postoperatively. The PSEP and PVP groups had an equivalent International Prostate Symptom Score, quality-of-life score, postvoid residual urine volume, maximum urine flow rate, prostate-specific antigen at each follow-up (P > 0.05). The median operative time in the PSEP group was significantly shorter than that in the PVP group (35 min vs. 47 min, P < 0.001). At 6 and 12 months after surgery, the median PV in the PSEP group was smaller than that in the PVP group (P < 0.05). Complication rates were comparable between the groups. CONCLUSION: Both PSEP and PVP can achieve good efficacy and safety in the treatment of BPH. PSEP can remove more tissue than PVP and is associated with higher efficiency. In addition, PSEP eliminates the problem of lack of tissue samples associated with PVP. TRIAL REGISTRATION: Chinese Clinical Trial Registry, identifie:ChiCTR1800015867, date:25/04/2018.

Photoselective sharp enucleation of the prostate with a front-firing 532-nm laser: an innovative surgical technique for benign prostatic hyperplasia-a single-center study of 475 cases.

PURPOSE: To describe the novel technique of photoselective sharp enucleation of the prostate (PSEP) with a front-firing 532-nm laser and evaluate its efficacy and safety. METHODS: A seven-step standardized surgical procedure was established, and PSEP was performed in an en bloc or lobulate manner according to the size of the middle lobe of the prostate. The following clinical data of 583 patients who underwent PSEP in our center from November 2016 to May 2018 were retrospectively reviewed: maximum flow rate (Qmax), International Prostate Symptom Score (IPSS), quality of life score (Qols), post-void residual volume (PVR), prostate volume, operation time, serum prostate-specific antigen (PSA) concentration, and complications at 1, 6, and 12 months postoperatively. RESULTS: Of the 583 patients, 475 had complete clinical information and were included in the study. The median operation time was 39 min. There were significant improvements in the Qmax, IPSS, Qols, PVR and PSA concentration at each follow-up time point postoperatively. Postoperative hemorrhage occurred in 22 patients (4.6%), urinary retention in 29 (6.1%), urinary tract infection in 55 (11.6%), bladder neck contracture in 8 (1.7%), urethral strictures in 11 (2.3%), and stress urinary incontinence in 9 (1.9%). CONCLUSIONS: PSEP is effective and safe for the treatment of benign prostatic hyperplasia. The innovative technique integrates the excellent hemostatic property of the 532-nm laser and the high efficiency of enucleation. It decreases the occurrence of postoperative incontinence associated with "blunt" enucleation of 532-nm laser and eliminates the lack of tissue samples problem associated with photoselective vaporization of the prostate.

MicroRNA-140 Represses Esophageal Cancer Progression via Targeting ZEB2 to Regulate Wnt/ß-Catenin Pathway.

BACKGROUND: MicroRNAs have been reported to play regulatory functions in various cancers, including esophageal cancer. The aim of this study was to investigate the effects of miR-140 on the progression of esophageal cancer and the underlying regulatory mechanism. METHODS: The levels of miR-140 and zinc finger E-box-binding homeobox 2 (ZEB2) messenger RNA in esophageal cancer tissues and cell lines were measured by quantitative real-time polymerase chain reaction. The protein levels of ZEB2, ß-catenin, c-Myc, and cyclinD1 were determined by Western blot. Cell proliferation and apoptosis were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay and flow cytometry, respectively. Cell migration and invasion were assessed by transwell assay. In addition, the relationship between miR-140 and ZEB2 was predicted by TargetScan online database and confirmed by dual-luciferase reporter assay. The tumor xenograft model was used to verify the role of miR-140 in esophageal cancer progression in vivo. RESULTS: The expression of miR-140 was downregulated whereas ZEB2 expression was upregulated in esophageal cancer tissues compared with paracancerous normal tissues. Functionally, both miR-140 overexpression and ZEB2 knockdown inhibited proliferation, migration, and invasion and induced apoptosis in esophageal cancer cells. ZEB2 overexpression reversed the effects of miR-140 on proliferation, apoptosis, migration, and invasion of esophageal cancer cells. Mechanistically, ZEB2 was identified as a target of miR-140. Furthermore, miR-140 suppressed Wnt/ß-catenin pathway by regulating ZEB2 expression in esophageal cancer cells. MiR-140 inhibited tumor growth of esophageal cancer through repressing ZEB2 expression in vivo. CONCLUSIONS: Our results demonstrated that miR-140 inhibited esophageal cancer development by targeting ZEB2 through inactivating Wnt/ß-catenin pathway.

Genetic characterization and phylogenetic analysis of duck-derived waterfowl parvovirus in Anhui province, eastern China.

Recently, a novel duck-origin goose parvovirus (N-GPV) was reported to cause short beak and dwarfism syndrome in ducks. In this study, we performed complete genome sequencing and analyzed three different duck-derived parvoviruses that infected different breeds of ducks. Phylogenetic trees based on gene sequences indicated that they were classical goose parvovirus (C-GPV), Muscovy duck parvovirus (MDPV), and N-GPV. Furthermore, potential recombination events were found. These results improve our understanding of the diversity of duck-derived parvoviruses in Anhui province, eastern China, and provide a reference for the prevention of associated diseases.

CircHACE1 functions as a competitive endogenous RNA to curb differentiated thyroid cancer progression by upregulating Tfcp2L1 through adsorbing miR-346.

Circular RNAs (circRNAs) are correlated with the occurrence and progression of differentiated thyroid cancer (THCA). However, the regulatory mechanism of circRNAs in differentiated THCA is unclear. In the present study, we analyzed the circRNA microarray dataset (GSE93522) of thyroid tumors and discovered that circRNA HACE1 (circHACE1) was downregulated in differentiated THCA. We detected circHACE1 expression by quantitative real-time polymerase chain reaction (qRT-PCR). Gain-of-function experiments were performed to analyze the biological function of circHACE1 in differentiated THCA cells in vitro. The regulatory mechanism of circHACE1 in differentiated THCA was explored through bioinformatics analysis, dual-luciferase reporter, RIP (RNA immunoprecipitation), and/or RNA pull-down assays. The biological function of circHACE1 in THCA was confirmed by xenograft assay. We verified that circHACE1 was downregulated in differentiated THCA. Also, differentiated THCA patients with low circHACE1 expression were associated with TNM grade, lymphoid node metastasis, tumor size, and poor prognosis. CircHACE1 overexpression decreased xenograft tumor growth in vivo and induced cell cycle arrest, apoptosis, impeded proliferation, migration, and invasion in differentiated THCA cells in vitro. CircHACE1 could function as a microRNA (miR)-346 sponge and regulated Tfcp2L1 (transcription factor CP2 like 1) expression. MiR-346 overexpression offset circHACE1 elevation-mediated effects on malignant behaviors of differentiated THCA cells. Furthermore, Tfcp2L1 silencing counteracted the suppressive impact of miR-346 inhibitor on the malignancy of differentiated THCA cells. In conclusion, circHACE1 adsorbed miR-346 and elevated Tfcp2L1 expression, thus curbing cell malignancy in differentiated THCA, manifesting that circHACE1 might be a target for differentiated THCA treatment.

Identification and fine mapping of a major locus controlling branching in Brassica napus.

KEY MESSAGE: A candidate branching-controlling gene for qDBA09 was identified after delimiting a Brassica napus recessive locus within a 270-kb interval on chromosome A09. Although branching is an important trait associated with the adaptation and yield potential of rapeseed (Brassica napus), the genetic mechanisms underlining branching in this crop remain poorly understood. In this study, we characterized a naturally occurring rapeseed mutant, db1, which showed an ultrahigh branching density phenotype. By combining bulked segregant analysis (BSA) and the Brassica 60K SNP BeadChip Array, we identified two major quantitative trait loci (QTLs), qDBA09 and qDBC06, which were subsequently confirmed using the traditional QTL-mapping approach. Analysis of 208 individuals from a BC1F3 population indicated that the qDBA09 locus is a single Mendelian factor and that the dense branching phenotype is controlled by a single recessive gene. Furthermore, QTL analysis confirmed that qDBA09 explained between 9.5 and 70.5% of the variation in branching-related traits. Using 7785 individuals from the BC1F3 population, we mapped qDBA09 to a DNA fragment of approximately 270 kb in length that contained 27 predicted genes, three of which were identified as potentially involved in the control of the dense branching trait. Based on the reported function of these genes, together with sequence comparisons and co-segregation analysis, we identified a potential candidate gene for the qDBA09 locus. The present findings lay the foundations for further in-depth research on the branching mechanisms of B. napus.

Fungal elicitor-induced transcriptional changes of genes related to branched-chain amino acid metabolism in Streptomyces natalensis HW-2.

Natamycin is a polyene macrolide antibiotic and widely used as a natural food preservative. Fungal elicitor had positive effects on the natamycin biosynthesis in Streptomyces natalensis HW-2. However, the global gene expression in response to fungal elicitor is not still reported. In the study, RNA-Seq was used to check the change of transcriptome by fungal elicitor in S. natalensis HW-2. The results showed that there were 1265 differential expression genes (DEGs) at 40 h and 2196 DEGs at 80 h. Most of the genes involved in natamycin biosynthesis were upregulated. KEGG pathway analysis showed that fungal elicitor had strong effects on the transcriptional levels of genes related to branch-chained amino acid (BCAA) metabolism. There were 23 upregulated or downregulated DEGs involved in BCAA biosynthesis and degradation at 40 h and 80 h. To confirm whether the improvement of BCAA biosynthesis could produce more natamycin, metabolic engineering was used to homologously overexpress the gene ilvH which encoded the regulatory subunit of acetolactate synthase (ALS) in S. natalensis. The results showed that overexpression of ilvH in S. natalensis HW-2 increased natamycin production to 1.25 g/L in the flask, which was a 32% increase compared with that of the parent strain. Real-time quantitative PCR analysis showed that the transcriptional level of ilvH in mutant strain S. natalensis ZS101 was significantly increased. Acetyl-CoA content was also raised. The results suggested that the fungal elicitor enhanced natamycin biosynthesis by improving precursor supply via BCAA metabolism. This study will open a new avenue for enhancing natamycin production by metabolic engineering and adding fungal elicitor. KEY POINTS: • The fungal elicitor had strong effects on the transcriptional levels of genes related to branch-chained amino acid metabolism by RNA-Seq. • The homologous overexpression of gene ilvH increased natamycin production by 32% and acetyl-CoA content was raised in mutant strain S. natalensis ZS101.

Clinical efficacy of submucosal injection of triamcinolone acetonide in the treatment of type II/III interstitial cystitis/bladder pain syndrome.

BACKGROUND: To evaluate the efficacy of submucosal injection of triamcinolone acetonide for the treatment of type II/III interstitial cystitis/bladder pain syndrome. METHODS: A retrospective analysis of the clinical data of type II/III interstitial cystitis/bladder pain syndrome patients treated in our department from April 2016 to August 2018 was conducted, and changes in International Prostate Symptom Scores and the Pelvic Pain and Urgency/Frequency symptom scale after surgery were evaluated to explore factors that may affect patient outcomes. RESULTS: A total of 27 female patients and 8 male patients were enrolled, with type II patients accounting for 62.9% of the sample, and the median follow-up duration was 31 months (range: 12-40 months). Twenty-two patients (74.3%) had significantly improved questionnaire scores at 4 weeks postoperatively. Treatment efficacy was sustained for at least 1 year in 15 patients, and persistent effectiveness was noted in 10 (28.6%) patients. Patients with an advanced age (p = 0.015), high pain scores (p = 0.040), and higher International Prostate Symptom Scores (p = 0.037) and Pelvic Pain and Urgency/Frequency symptom scale scores (p = 0.020) were more likely to benefit from submucosal injection of triamcinolone acetonide. Gender, disease duration, and the presence of Hunner's lesions had no predictive value for treatment outcomes. CONCLUSION: Submucosal injection of triamcinolone acetonide can improve the clinical symptoms and quality of life in both men and women with type II/III interstitial cystitis/bladder pain syndrome. Patients with an advanced age and more severe interstitial cystitis/bladder pain syndrome related symptoms may benefit more from triamcinolone acetonide injection.

Association between polymorphisms in mannose-binding lectin 2 gene with pulmonary tuberculosis susceptibility.

BACKGROUND: Mannose-binding lectin (MBL2) is considered to play a role in the human innate immune response to tuberculosis (TB) infections, and 4 common single nucleotide polymorphisms (SNPs) may be associated with pulmonary tuberculosis (PTB) risk. To examine these potential associations, we performed a comprehensive analysis to assess the relationships between MBL2 polymorphisms and PTB. METHODS: The PubMed, Embase, and SinoMed databases were searched for articles published prior to June 13, 2019. Odds ratios with 95% confidence intervals were calculated to evaluate the strength of the relationships. RESULTS: There were 37 case-control studies examining the effects of the four SNPs in MBL2 on PTB. A positive association between rs11003125 and PTB risk was observed in the hospital-based subgroup. Moreover, for the combined polymorphism and PTB risk, positive associations were detected not only in the total population but also in those with Asian origins across all source of control subgroups. No associations were found for rs7096206 or rs7095891. CONCLUSIONS: Our current study indicated that several SNPs in MBL2 may be associated with susceptibility to PTB.

Fine mapping of a silique length- and seed weight-related gene in Brassica napus.

KEY MESSAGE: Using microarray analysis combined with map-based cloning, a major locus positively regulating SL and SW was mapped to a 98.47 kb interval on A09 in rapeseed. In rapeseed, seed yield is closely associated with silique-related traits such as silique length (SL) and seed weight (SW). Previously identified quantitative trait loci (QTLs) revealed that SL and SW are complex traits and many QTLs overlap. However, the genetic characterization of the association between SL and SW is poorly understood. In the present study, a BC3F3 near isogenic line developed from a short silique plant and the long silique cultivar 'ZS11' was analyzed to identify the locus related to SL. Map-based cloning indicated that a major locus acting as a single Mendelian factor was mapped to a 98.47 kb region on chromosome A09. BLAST analysis and DNA sequencing showed SNP variations and a fragment replacement in the upstream region of the candidate gene BnaA09g55530D may alter gene expression and influence SL. The results showed that this SL locus may also positively affect SW as well as in the 186 rapeseed accessions identified by the associated markers. Therefore, selecting plants with appropriate SL and developing functional markers for the associated gene could play important roles in the molecular breeding of high-yield rapeseed varieties.

Fabrication and application of nanoporous polymer ion-track membranes.

With the development of the nano-fabrication and nanofluidics, nanoporous membranes have shown great potential in applications such as molecular separation, energy conversion, and molecular sensing. However, their performance has often been limited by the trade-off between selectivity and permeability and the lack of scalability. The prospect of overcoming these problems with nanoporous polymer ion-track membranes is promising. Focusing on these membranes, this review provides a comprehensive overview of fabrication methods, including the traditional track-etching technique and the recently developed track-UV technique; characterization methods; transport mechanisms; and major properties and applications.

On-line chemical oxygen demand estimation models for the photoelectrocatalytic oxidation advanced treatment of papermaking wastewater.

Chemical oxygen demand (COD), an important indicative measure of the amount of oxidizable pollutants in wastewater, is often analyzed off-line due to the expensive sensor required for on-line analysis. However, its off-line analysis is time-consuming. An on-line COD estimation method was developed with photoelectrocatalytic (PEC) technology. Based on the on-line data of the oxidation-reduction potential (ORP), dissolved oxygen (DO) and pH of wastewater, four different artificial neural network methods were applied to develop working models for COD estimation. Six different batches of sequence batch reactor (SBR) effluent from a paper mill were treated with PEC oxidation for 90 minutes, and 546 data points were collected from the on-line measurements of ORP, DO and pH, and the off-line COD analysis. After having training and validation with 75% and 25% of data, and evaluation with four statistical criteria (R2, RMSE, MAE and MAPE), the estimation results indicated that the developed radial basis neural network (RBNN) model demonstrated the highest precision. Subsequently, the application of the RBNN model to a new batch of SBR effluent from the paper mill revealed that the RBNN model was acceptable for COD estimation during the PEC advanced treatment process of papermaking wastewater, which implied its possible application in the future.