Indole alkaloids isolated from the Nicotiana tabacum-derived Aspergillus fumigatus 0338 as potential inhibitors for tobacco powdery mildew and their mode of actions.

To explore active natural products against tobacco powdery mildew caused by Golovinomyces cichoracearum, an extract from the fermentation of endophytic Aspergillus fumigatus 0338 was investigated. The mechanisms of action for active compounds were also studied in detail. As a result, 14 indole alkaloid derivatives were isolated, with seven being newly discovered (1-7) and the remaining seven previously described (8-14). Notably, compounds 1-3 are rare linearly fused 6/6/5 tricyclic prenylated indole alkaloids, with asperversiamide J being the only known natural product of this kind. The isopentenyl substitutions at the 5-position in compounds 4 and 5 are also rare, with only compounds 1-(5-prenyl-1H-indol-3-yl)-propan-2-one (8) and 1-(6-methoxy-5-prenyl-1H-indol3-yl)-propan-2-one currently available. In addition, compounds 6 and 7 are new framework indole alkaloid derivatives bearing a 6-methyl-1,7-dihydro-2H-azepin-2-one ring. The purified compounds were evaluated for their activity against G. cichoracearum, and the results revealed that compounds 7 and 9 demonstrated obvious anti-G. cichoracearum activities with an inhibition rate of 82.6% and 85.2%, respectively, at a concentration of 250 µg/mL, these rates were better than that of the positive control agent, carbendazim (78.6%). The protective and curative effects of compounds 7 and 9 were also better than that of positive control, at the same concentration. Moreover, the mechanistic study showed that treatment with compound 9 significantly increased the structural tightness of tobacco leaves and directly affect the conidiospores of G. cichoracearum, thereby enhancing resistance. Compounds 7 and 9 could also induce systemic acquired resistance (SAR), directly regulating the expression of defense enzymes, defense genes, and plant semaphorins, which may further contribute to increased plant resistance. Based on the activity experiments and molecular dockings, the indole core structure may be the foundation of these compounds' anti-G. cichoracearum activity. Among them, the indole derivative parent structures of compounds 6, 7, and 9 exhibit strong effects. Moreover, the methoxy substitution in compound 7 can enhance their activity. By isolating and structurally identifying the above indole alkaloids, new candidates for anti-powdery mildew chemical screening were discovered, which could enhance the utilization of N. tabacum-derived fungi in pesticide development.

Assessment of monthly runoff simulations based on a physics-informed machine learning framework: The effect of intermediate variables in its construction.

Hydrological forecasting is of great importance for water resources management and planning, especially given the increasing occurrence of extreme events such as floods and droughts. The physics-informed machine learning (PIML) models effectively integrate conceptual hydrologic models with machine learning (ML) models. In this process, the intermediate variables of PIML models serve as bridges between inputs and outputs, while the impact of intermediate variables on the performance of PIML models remains unclear. To fill this knowledge gap, this study aims to encompass the construction of PIML models based on various hydrologic models, conduct comparative analyses of different intermediate variables based on a case study of 205 CAMELS basins, and further explore the relationship between the performance of PIML models and catchment characteristics. The optimal ML model for constructing PIML is first selected among four ML models within the 205 basins. The PIML models are then developed based on five monthly water balance models, namely TM, XM, MEP, SLM, and TVGM. To quantify the potential impact of difference in intermediate variables, two sets of experiments are further designed and performed, namely S1 with actual evapotranspiration as the intermediate variable and S2 with soil moisture as the intermediate variable. Results show that five PIML models generally outperformed the optimal standalone ML models, i.e., the Lasso model. Specifically, regardless of the choice of intermediate variables, the PIML-XM model consistently outperformed the other models within the same basins. Almost all constructed PIML models are affected by the intermediate variables in monthly runoff simulations. Typically, S1 exhibited better performance compared to S2. A greater impact of aridity index, forest fraction, and catchment area on model performance is observed in S2. These findings improve our understanding of constructing PIML models in hydrology by emphasizing their excellent performance in runoff simulations and highlighting the importance of intermediate variables.

Mechanism Behind the Programmed Biosynthesis of Heterotrimeric Fungal Depside Thielavin A.

Thielavin A (1) is a fungal depside composed of one 3-methylorsellinic acid and two 3,5-dimethylorsellinic acid units. It displays diverse biological activities. However, the mechanism underlying the assembly of the heterotrimeric structure of 1 remains to be clarified. In this study, we identified the polyketide synthase (PKS) involved in the biosynthesis of 1. This PKS, designated as ThiA, possesses an unusual domain organization with the C-methyltransferase (MT) domain situated at the C-terminus following the thioesterase (TE) domain. Our findings indicated that the TE domain is solely responsible for two rounds of ester bond formation, along with subsequent chain hydrolysis. We identified a plausible mechanism for TE-catalyzed reactions and obtained insights into how a single PKS can selectively yield a specific heterotrimeric product. In particular, the tandem acyl carrier protein domains of ThiA are critical for programmed methylation by the MT domain. Overall, this study highlighted the occurrence of highly optimized domain-domain communication within ThiA for the selective synthesis of 1, which can advance our understanding of the programming rules of fungal PKSs.

Ketoreductase Domain-Catalyzed Polyketide Chain Release in Fungal Alkyl Salicylaldehyde Biosynthesis.

Alkyl salicylaldehyde derivatives are polyketide natural products, which are widely distributed in fungi and exhibit great structural diversity. Their biosynthetic mechanisms have recently been intensively studied; however, how the polyketide synthases (PKSs) involved in the fungal alkyl salicylaldehyde biosyntheses release their products remained elusive. In this study, we discovered an orphan biosynthetic gene cluster of salicylaldehyde derivatives in the fungus Stachybotrys sp. g12. Intriguingly, the highly reducing PKS StrA, encoded by the gene cluster, performs a reductive polyketide chain release, although it lacks a C-terminal reductase domain, which is typically required for such a reductive release. Our study revealed that the chain release is achieved by the ketoreductase (KR) domain of StrA, which also conducts cannonical ß-keto reductions during polyketide chain elongation. Furthermore, we found that the cupin domain-containing protein StrC plays a critical role in the aromatization reaction. Collectively, we have provided an unprecedented example of a KR domain-catalyzed polyketide chain release and a clearer image of how the salicylaldehyde scaffold is generated in fungi.

Climate-driven vegetation greening further reduces water availability in drylands.

Climate change alters surface water availability (WA; precipitation minus evapotranspiration, P - ET) and consequently impacts agricultural production and societal water needs, leading to increasing concerns on the sustainability of water use. Although the direct effects of climate change on WA have long been recognized and assessed, indirect climate effects occurring through adjustments in terrestrial vegetation are more subtle and not yet fully quantified. To address this knowledge gap, here we investigate the interplay between climate-induced changes in leaf area index (LAI) and ET and quantify its ultimate effect on WA during the period 1982-2016 at the global scale, using an ensemble of data-driven products and land surface models. We show that ~44% of the global vegetated land has experienced a significant increase in growing season-averaged LAI and climate change explains 33.5% of this greening signal. Such climate-induced greening has enhanced ET of 0.051 ± 0.067 mm year-2 (mean ± SD), further amplifying the ongoing increase in ET directly driven by variations in climatic factors over 36.8% of the globe, and thus exacerbating the decline in WA prominently in drylands. These findings highlight the indirect impact of positive feedbacks in the land-climate system on the decline of WA, and call for an in-depth evaluation of these phenomena in the design of local mitigation and adaptation plans.

LncRNA WEE2-AS1 is a diagnostic biomarker that predicts poor prognoses in patients with glioma.

BACKGROUND: Glioma is characterized by high morbidity, high mortality, and poor prognosis. Despite tremendous advances in the treatment of glioma, the prognosis of patients with glioma is still unsatisfactory. There is an urgent need to discover novel molecular markers that effectively predict prognosis in patients with glioma. The investigation of the role of WEE2-AS1 in various tumors is an emerging research field, but the biological function and prognostic value of WEE2-AS1 in glioma have rarely been reported. This study aimed to assess the value of WEE2-AS1 as a potential prognostic marker of glioma. METHODS: Gene expression (RNA-Seq) data of patients with glioma were extracted from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. The Wilcoxon rank sum test was used to analyze the expression of WEE2-AS1 in the cells and tissues of glioma. The Kruskal-Wallis rank sum test, Wilcoxon rank sum test, and logistic regression were used to evaluate the relationship between clinical variables and expression of WEE2-AS1. Cox regression analysis and the Kaplan-Meier method were used to evaluate the prognostic factors in glioma. A nomogram based on Cox multivariate analysis was used to predict the impact of WEE2-AS1 on glioma prognosis. Gene Set Enrichment Analysis (GSEA) was used to identify key WEE2-AS1-associated signaling pathways. Spearman's rank correlation was used to elucidate the association between WEE2-AS1 expression and immune cell infiltration levels. RESULTS: We found that WEE2-AS1 was overexpressed in a variety of cancers, including glioma. High expression of WEE2-AS1 was associated with glioma progression. We determined that the expression of WEE2-AS1 might be an independent risk factor for the survival and prognosis of patients with glioma. We further observed that the mechanism of WEE2-AS1-mediated tumorigenesis involved neuroactive ligand-receptor interaction, cell cycle, and the infiltration of immune cells into the glioma microenvironment. CONCLUSION: These findings demonstrate that WEE2-AS1 is a promising biomarker for the diagnosis and prognosis of patients with glioma. An increased understanding of its effects on the regulation of cell growth may lead to the development of clinical applications that improve the prognostic status of patients with glioma.

Extraction and characterization of anti-virus anthraquinones from Nicotiana tabacum-derived Aspergillus oryzae YNCA1220.

In this study, seven novel anthraquinones (1-7) and four described anthraquinones (8-11) were purified from Nicotiana tabacum-derived Aspergillus oryzae YNCA1220. It is worth noting that only analogs of 4 and 5 have been reported as natural products to date, while the nuclei of compounds 1-3, 6 and 7 were isolated for the first time in nature. Among them, compounds 1-3 bear an unusual anthra[2,3-b]furan-9,10-dione nucleus, 4 and 5 possess a rare 3-methyl-1H-pyrrol-2-yl substituent, and 6 and 7 are new framework anthraquinones bearing a 6-methyl-1,7-dihydro-2H-azepin-2-one ring. Interestingly, the in vivo assays indicated that 1, 4 and 5 had inactivation effects against tobacco mosaic virus (TMV) with inhibition rates of 41.6%, 55.4% and 38.6%, respectively, at a concentration of 50 µg/mL, which were better than that of the positive control agent, ningnanmycin (33.8%). Compounds 1, 4 and 5 also had protective effects with inhibition rates of 48.7%, 60.2% and 43.5% at the same concentration, while 4 had a better curative effect than ningnanmycin at a concentration of 100 µg/mL. In addition, mechanistic studies also revealed that a potent direct effect on TMV, the induction of SAR in tobacco plants, and the effective regulation of defense enzymes, defense genes, and defense hormones may be the reasons for the significant effects of 4 against TMV. At the same time, downregulation of the expression of total NtHsp70 protein by inhibiting the related Hsp70 genes may also be involved in tobacco resistance to TMV. To evaluate whether compounds have broader antiviral activities, the antirotavirus activities of new isolates were also evaluated and found to be highly effective with a therapeutic index (TI) value ranging from 11.6 to 17.7. This study suggests that the above anthraquinone compounds, particularly 4, have broad spectrum antiviral activities. The successful isolation and structure identification of the above anthraquinones provide new materials for the screening of anti-TMV agents and contribute to the improved utilization of N. tabacum-derived fungi.

Two New Eudesmane-Type Sesquiterpene from Clonostachys sp. Y6-1and Their Cytotoxic Activity.

Two undescribed eudesmane-type sesquiterpenoids together with four known compounds were isolated from Clonostachys sp. Y6-1 associated. Their chemical structures were unambiguously determined by NMR, mass spectrometry, and 13 C-NMR calculation as well as DP4+ probability analyses. The absolute configurations of compounds 1 and 2 were determined by ECD calculation and X-ray single-crystal diffraction methods. Furthermore, all isolates were evaluated for in vitro cytotoxic activities against MCF-7, HCT-116, MDA-MB-231, and SW620 cancer cells. Among them, bioactivity evaluation of compound 5 revealed that weak activity (IC50 =66.55±0.82 µM) against SW620.

UAV-Assisted Cluster-Based Task Allocation for Mobile Crowdsensing in a Space-Air-Ground-Sea Integrated Network.

Mobile crowdsensing (MCS), which is a grassroots sensing paradigm that utilizes the idea of crowdsourcing, has attracted the attention of academics. More and more researchers have devoted themselves to adopting MCS in space-air-ground-sea integrated networks (SAGSINs). Given the dynamics of the environmental conditions in SAGSINs and the uncertainty of the sensing capabilities of mobile people, the quality and coverage of the sensed data change periodically. To address this issue, we propose a novel UAV-assisted cluster-based task allocation (UCTA) algorithm for MCS in SAGSINs in a two-stage process. We first introduce the edge nodes and establish a three-layer hierarchical system with UAV-assistance, called "Platform-Edge Cluster-Participants". Moreover, an edge-aided attribute-based cluster algorithm is designed, aiming at organizing tasks into clusters, which significantly diminishes both the communication overhead and computational complexity while enhancing the efficiency of task allocation. Subsequently, a greedy selection algorithm is proposed to select the final combination that performs the sensing task in each cluster. Extensive simulations are conducted comparing the developed algorithm with the other three benchmark algorithms, and the experimental results unequivocally endorse the superiority of our proposed UCTA algorithm.

Regulatory effect of isovitexin on MAPK/NF-κB signal in mice with acute ulcerative colitis.

The aim of this study was to investigate the anti-inflammatory effects and mechanism of isovitexin on ulcerative colitis mice and RAW264.7 cells. The results showed that isovitexin had strong antioxidant and anti-inflammatory effects, and could restore intestinal barrier integrity (p < 0.01). In addition, isovitexin inhibited the expression of MyD88, TLR4 and NF-κB p65 proteins. At the same time, isovitexin can inhibit the activation of MAPK/NF-κB signaling pathway in RAW264.7 cells. In conclusion, isovitexin has a protective effect on UC mice, and its improvement mechanism of UC might be related to MAPK/NF-κB signaling pathway.

Evaluating main drivers of runoff changes across China from 1956 to 2000 by using different budyko-based elasticity methods.

The Budyko-based elasticity method has been widely employed to clarify the driving factors behind runoff changes. However, different formulations of the Budyko framework could produce biases in the elasticity analysis and the assessment errors induced from different formulations of the Budyko framework in the elasticity method remain unclear. Here, we attempt to address this issue by validating the performance of elasticity methods derived from two analytical Budyko equations (Fu's equation and Choudhury's equation), as well as one empirical Budyko equation (Wang-Tang's equation) of the Budyko framework across 22 basins in China. Validations show that the runoff change simulated by the elasticity method derived from the empirical equation has lower errors compared with the two analytical Budyko equations. Results reveal that in the semi-humid environment, the alteration of basin characteristics takes the main responsibility for the runoff change. However, a clear divergence was found in simulated runoff changes among different Budyko-based elasticity methods in humid basins. For parts of the humid basin, the precipitation is the main driver of runoff change from the analytical Budyko-based elasticity methods, while the alteration of basin characteristics is the main derive of the runoff changes according to based on the empirical Budyko-based elasticity method. This difference could be attributed to the variations in the simulated contributions from the alteration of basin characteristics on runoff changes. Generally, our results highlight the importance of validating different Budyko equations when applying the elasticity method to investigate the driver of the runoff changes in humid regions.

[Tonglong Kaibi Prescription for the treatment of severe benign prostate hyperplasia: A clinical study].

OBJECTIVE: To evaluate the clinical effect of the traditional Chinese medicine (TCM) Tonglong Kaibi Prescription (TKP) in the treatment of severe BPH with kidney deficiency and blood stasis combined with damp heat syndrome. METHODS: We randomly divided 120 cases of severe BPH with kidney deficiency and blood stasis combined with damp heat syndrome into three groups of equal number, treated with TKP, doxazosin mesylate sustained-release tablets (the DM control), and TKP + DM, all for 8 weeks. We obtained the IPSS, TCM symptoms scores, quality of life (QOL) scores, maximum urinary flow rate (Qmax) and postvoid residual urine volume (PVR) from the patients before and after treatment and compared them among the three groups. RESULTS: After 8 weeks of treatment, the effectiveness rate was significantly higher in the TKP + DM than in the DM control group (P < 0.05). The IPSS, TCM symptoms scores, QOL scores and PVR decreased (P < 0.01), while the Qmax increased dramatically (P < 0.01) in all the three groups. Pairwise comparison showed that the IPSS and QOL scores were lower in the TKP + DM than in the TKP and DM control groups (P < 0.05 or 0.01), and so were the TCM syndrome scores in the TKP + DM and TKP groups than in the DM control (P < 0.01). There were no statistically significant differences in PVR and Qmax among the three groups after treatment (P> 0.05), and no serious adverse events during the treatment. CONCLUSION: TKP is safe and effective in the treatment of severe BPH, which can improve the TCM symptoms, reduce the IPSS, QOL scores and PVR and increase the Qmax of the patients. TKP is evidently superior to DM alone in improving TCM symptoms of BPH and combined medication of TKP and DM produces even better clinical efficacy.

Aspulvins A-H, Aspulvinone Analogues with SARS-CoV-2 Mpro Inhibitory and Anti-inflammatory Activities from an Endophytic Cladosporium sp.

Eight new aspulvinone analogues, aspulvins A-H (1-8) and aspulvinones D, M, O, and R (9-12), were isolated from cultures of the endophytic fungus Cladosporium sp. 7951. Detailed spectroscopic analyses were conducted to determine the structures of the new compounds. All isolates displayed different degrees of inhibitory activity against the severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2 Mpro) at 10 µM. Notably, compounds 9, 10, and 12 showed potential SARS-CoV-2 Mpro inhibition with IC50 values of 10.3 ± 0.6, 9.4 ± 0.6, and 7.7 ± 0.6 µM, respectively. For all compounds except 3 and 4, the anti-inflammatory activity occurred by inhibiting the release of lactate dehydrogenase (LDH) with IC50 values ranging from 0.7 to 7.4 µM. Compound 10 showed the most potent anti-inflammatory activity by inhibiting Casp-1 cleavage, IL-1ß maturation, NLRP3 inflammasome activation, and pyroptosis. The findings reveal that the aspulvinone analogues 9, 10, and 12 could be promising candidates for coronavirus disease 2019 (COVID-19) treatment as they inhibit SARS-CoV-2 infection and reduce inflammatory reactions caused by SARS-CoV-2.

The TGFß type I receptor TGFßRI functions as an inhibitor of BMP signaling in cartilage.

The type I TGFß receptor TGFßRI (encoded by Tgfbr1) was ablated in cartilage. The resulting Tgfbr1Col2 mice exhibited lethal chondrodysplasia. Similar defects were not seen in mice lacking the type II TGFß receptor or SMADs 2 and 3, the intracellular mediators of canonical TGFß signaling. However, we detected elevated BMP activity in Tgfbr1Col2 mice. As previous studies showed that TGFßRI can physically interact with ACVRL1, a type I BMP receptor, we generated cartilage-specific Acvrl1 (Acvrl1Col2 ) and Acvrl1/Tgfbr1 (Acvrl1/Tgfbr1Col2) knockouts. Loss of ACVRL1 alone had no effect, but Acvrl1/Tgfbr1Col2 mice exhibited a striking reversal of the chondrodysplasia seen in Tgfbr1Col2 mice. Loss of TGFßRI led to a redistribution of the type II receptor ACTRIIB into ACVRL1/ACTRIIB complexes, which have high affinity for BMP9. Although BMP9 is not produced in cartilage, we detected BMP9 in the growth plate, most likely derived from the circulation. These findings demonstrate that the major function of TGFßRI in cartilage is not to transduce TGFß signaling, but rather to antagonize BMP signaling mediated by ACVRL1.

Two new sesquiterpene aryl esters from Armillaria gallica 012m.

Two new sesquiterpene aryl esters, armimelleolides A and B (1 and 2), and four known ones, were isolated from the EtOAc extract of Armillaria gallica 012 m by column chromatography on silica gel, reversed-phase C18 silica gel and semi-preparative HPLC. Their structures were elucidated on the basis of spectroscopic methods, including extensive 1 D NMR, 2 D NMR and MS. All these compounds showed potential antitumor activities against at least one of the human cancer cell lines (A549, HCT-116, M231 and W256), with IC50 ranging from 2.57 to 19.94 µM.

[Danhong Tongjing Prescription versus microsurgery in the treatment of varicocele-induced infertility: A retrospective multivariate analysis of 218 cases].

OBJECTIVE: To compared the traditional Chinese medicine Danhong Tongjing Prescription (DTP) and microsurgery in the treatment of varicocele (VC)-induced infertility and investigate the factors influencing the recovery of semen parameters of the patients. METHODS: We retrospectively analyzed the clinical data on 218 cases of VC-induced infertility with qi-deficiency and blood-stasis treated with DTP (n = 86) or by microsurgery (n = 132) in our hospital from January 2017 to July 2019, and compared the semen parameters between the two groups of patients after treatment. With age, course of disease, degree of VC, change of the testis volume, estrogen/testosterone (E/T) ratio and levels of FSH and LH as independent variables, and increased semen parameters after treatment as dependent variables, we constructed a multivariate linear regression model and identified statistically significant independent variables. RESULTS: After treatment, sperm concentration and the percentages of progressively motile sperm (PMS) and morphologically normal sperm (MNS) were obviously improved in both the DTP and microsurgery groups, with statistically significant difference between the two groups in sperm concentration and MNS, but not in PMS. Linear regression analysis showed that the severity of VC was an influencing factor for the recovery of sperm concentration after treatment in the DTP group (r = －11.599, Ra2 = 0.044 9) and the course of VC infertility was a factor affecting the recovery of sperm count in the microsurgery group (r = －1.837, Ra2 = 0.035 7). CONCLUSION: DTP is comparable to microsurgery in improving sperm motility while microsurgery is more effective in increasing the percentage of MNS in the treatment of VC-induced infertility. Early surgery is recommended for the treatment of infertility induced by severe bilateral VC, and DTP can be selected for infertility caused by mild or moderate bilateral VC if the patient is unwilling to accept surgery or microsurgery is inaccessible in the hospital.

[Pricking-reinforcing -reducing therapy improves semen quality and seminal plasma biochemical indexes in patients with varicocele infertility].

OBJECTIVE: To investigate the effect of pricking-reinforcing -reducing therapy (PRRT) on the semen quality and seminal plasma biochemical indexes of varicocele (VC) infertility patients. METHODS: We randomly and equally assigned 160 patients with VC infertility into a PRRT and a control group, the former treated by PRRT and the latter with oral ShengjingCapsules. Before and after treatment, we obtained the semen parameters, sperm morphology, sperm survival rate, sperm acrosin activity, seminal plasma neutral α glucosidase and seminal plasma zinc in the patients and compared them between the two groups. RESULTS: Before treatment, there were no statistically significant differences between the PRRT and control groups in sperm concentration (ï¼»16.81 ± 7.83ï¼½ vs ï¼»16.80 ± 7.54ï¼½ ×106 /ml, P > 0.05), total sperm count (ï¼»42.01 ± 19.57ï¼½ vs ï¼»41.99 ± 18.84ï¼½ ×106, P > 0.05), percentages of progressively motile sperm (PMS) (ï¼»15.37 ± 11.03ï¼½% vs ï¼»14.68 ± 10.27ï¼½%, P > 0.05) and morphologically normal sperm ( MNS) (1.62 ± 1.51ï¼½% vs ï¼»1.62 ± 1.13ï¼½%, P > 0.05), sperm survival rate (ï¼»28.11 ± 18.95ï¼½% vs ï¼»28.23±18.38ï¼½%, P > 0.05) and sperm acrosin activity (ï¼»28.11 ± 14.64ï¼½ vs ï¼»27.19 ± 14.07ï¼½ U/L, P > 0.05). After three months of treatment, all the patients showed evident increases in the above parameters (P < 0.05), even higher in the PRRT than in the control group, more significantly in sperm concentration (ï¼»38.88 ± 30.54ï¼½ vs ï¼»25.60 ± 14.71ï¼½ ×106 /ml, P < 0.05), PMS (ï¼»32.60 ± 12.46ï¼½% vs ï¼»27.67 ± 12.27ï¼½%, P < 0.05) and sperm acrosin activity (ï¼»65.74±31.81ï¼½ vs ï¼»67.94±17.95ï¼½ U/L, P < 0.05), though not significantly in total sperm count (97.20 ± 76.35ï¼½ vs ï¼»88.19 ± 39.56ï¼½ ×106, P > 0.05), MNS (ï¼»2.35 ± 1.83ï¼½% vs ï¼»1.87 ± 1.20ï¼½%, P > 0.05) and sperm survival rate (ï¼»61.44 ± 20.02ï¼½% vs ï¼»59.12 ± 22.48ï¼½%, P > 0.05). Compared with the baseline, after treatment, the patients in the PRRT group also exhibited elevated levels of neutral α-glucosidase (ï¼»14.42 ± 5.90ï¼½ vs ï¼»28.43 ± 19.76ï¼½ U/L, P < 0.05) and seminal plasma zinc (ï¼»2.11 ± 1.22ï¼½ vs ï¼»2.89 ± 1.23ï¼½ mmol/L, P < 0.05), and so did the controls (ï¼»14.44 ± 5.61ï¼½ vs ï¼»26.66 ± 17.69ï¼½ U/L , P < 0.05) and (ï¼»2.09 ± 1.10ï¼½ vs ï¼»2.82±1.08ï¼½ mmol/L, P < 0.05). No statistically significant difference, however, was observed between the two groups after treatment (P > 0.05). CONCLUSION: PRRT can significantly improve semen quality in patients with VC infertility, even more effective than ShengjingCapsules in improving sperm concentration, PMS, sperm survival rate, and sperm acrosin activity, which may be related to its effect of elevating the levels of seminal plasma neutral-α glucosidase and zinc providing sufficient energy for basic sperm metabolism, maturation, energy acquisition and motility.

[Magnetic resonance and magnetoelectric therapy combined with Danhong Tongjing Prescription for the treatment of CP/CPPS and its effects on secretory IgA, vascular cell adhesion molecule-1 and interleukin-8].

OBJECTIVE: To investigate the therapeutic effect of magnetic resonance and magnetoelectric therapy (MRMT) combined with oral Danhong Tongjing Prescription (DTP) on chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS) and the changes in the levels of cytokine-secretory IgA (sIgA), vascular cell adhesion molecule-1 (VCAM-1) and interleukin-8 (IL-8) after treatment. METHODS: Totally 200 patients with CP/CPPS of the qi stagnation and blood stasis type were randomly divided into three groups to receive MRMT + DTP (n = 68), MRMT (n = 67) and DTP (n = 65), respectively, all for 12 weeks. After treatment, we compared the total effectiveness rate, patients' scores on NIH-CPSI and traditional Chinese medicine (TCM) syndrome, and the expressions of sIgA, VCAM-1 and IL-8 in the EPS among the three groups of the patients. RESULTS: After treatment, the patients in the MRMT + DTP group, compared with those in the MRMT and DTP groups, showed a significantly higher total effectiveness rate (86.76% vs 79.10% and 78.46%, P < 0.05 and P < 0.01) and lower scores on pain or discomfort (4.61 ± 2.37 vs 5.86 ± 3.26 and 6.94 ± 2.25 P < 0.01), abnormal urination symptoms (2.98 ± 1.75 vs 3.85 ± 2.01 and 3.94 ± 1.95) and quality of life (3.26 ± 1.87 vs 4.54 ± 2.13 and 4.69 ± 1.72). There were statistically significant differences in the total NIH-CPSI scores among the three groups (10.64 ± 5.91 vs 4.59 ± 6.87 vs 15.54 ± 5.76, P < 0.05). The MRMT + DTP group also exhibited a remarkably lower TCM syndrome score than the MRMT and DTP groups (5.56 ± 3.42 vs 7.37 ± 4.57 and 8.16 ± 3.65, P < 0.05). Compared with the baseline, the expressions sIgA, VCAM-1 and IL8 were all markedly decreased after treatment in the MRMT + DTP (Z = －7.170, Z = －7.182, Z = －7.18), MRMT (Z = －6.802, Z = －6.973, Z = －6.768) and DTP groups (Z = －5.963, Z = －6.990 Z = －5.618) (P < 0.05), even more significantly in the former than in the latter two groups (P < 0.05). CONCLUSION: Magnetic resonance and magnetoelectric therapy combined with Danhong Tongjing Prescription has a good therapeutic effect on CP/CPPS of the qi stagnation and blood stasis type, probably by regulating sIgA, VCAM-1, IL-8 and other cytokines, activating the function of the immune system, inhibiting inflammation, and promoting the absorption of local inflammatory substances.

Heterologous Biosynthesis of Tetrahydroxanthone Dimers: Determination of Key Factors for Selective or Divergent Synthesis.

Tetrahydroxanthone dimers are fungal products, among which secalonic acid D (1) is one of the most studied compounds because of its potent biological activity. Because the biosynthetic gene cluster of 1 has been previously identified, we sought to heterologously produce 1 in Aspergillus oryzae by expressing the relevant biosynthetic genes. However, our initial attempt of the total biosynthesis of 1 failed; instead, it produced four isomers of 1 due to the activity of an endogenous enzyme of A. oryzae. Subsequent overexpression of the Baeyer-Villiger monooxygenase, AacuH, which competes with the endogenous enzyme, altered the product profile and successfully generated 1. Characterization of the key biosynthetic enzymes revealed the surprising substrate promiscuity of the dimerizing enzyme, AacuE, and indicated that efficient synthesis of 1 requires highly selective preparation of the tetrahydroxanthone monomer, which is apparently controlled by AacuH. This study facilitates engineered biosynthesis of tetrahydroxanthone dimers both in a selective and divergent manner.

[Lingze Tablets for BPH with kidney-deficiency, blood stasis and dampness resistance: A phase-â £ open-label single-arm multicenter clinical study and safety evaluation].

OBJECTIVE: To evaluate the efficacy and safety of Lingze Tablets in the treatment of BPH with kidney deficiency, blood stasis and dampness resistance. METHODS: Totally 235 eligible BPH patients, aged 50－80 years and meeting the inclusion criteria, were enrolled and treated with Lingze Tablets orally, 4 tablets per time, tid. Before and after an 8-week course of medication, IPSS, quality of life (QOL) and TCM syndromes scores were obtained from the patients. RESULTS: Of the total number of patients, 211 completed the whole course of treatment. Compared with the baseline, the IPSS was dramatically reduced after 4 and 8 weeks of medication (18.28 ± 5.29 vs 12.82 ± 4.66 and 9.23 ± 4.21, P < 0.01), and so were the QOL scores (6.44 ± 1.99 vs 4.95 ± 1.64 and 3.16 ± 1.53, P < 0.01) and TCM syndromes scores (17.49 ± 5.30 vs 12.45 ± 3.74 and 9.17 ± 3.24, P < 0.01). The incidence rates of adverse events and drug-related adverse reactions were 15.2% and 1.9%, respectively, and no organ function impairment was observed. CONCLUSIONS: Lingze Tablets are definitely effective and safe for the treatment of BPH with kidney deficiency, blood stasis and dampness resistance.