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Background: Actinomycete genome sequencing has disclosed a large number of cryptic secondary metabolite biosynthetic gene clusters. However, their unavailable or limited expression severely hampered the discovery of bioactive compounds. The whiB-like (wbl) regulatory genes play important roles in morphological differentiation as well as secondary metabolism; and hence the wblAso gene was probed and set as the target to activate cryptic gene clusters in deepsea-derived Streptomyces somaliensis SCSIO ZH66. Results: wblAso from deepsea-derived S. somaliensis SCSIO ZH66 was inactivated, leading to significant changes of secondary metabolites production in the ΔwblAso mutant, from which a-pyrone compound violapyrone B (VLP B) was isolated. Subsequently, the VLP biosynthetic gene cluster was identified and characterized, which consists of a type III polyketide synthase (PKS) gene vioA and a regulatory gene vioB; delightedly, inactivation of vioB led to isolation of another four VLPs analogues, among which one was new and two exhibited improved anti-MRSA (methicillin-resistant Staphylococcus aureus, MRSA) activity than VLP B. Moreover, transcriptional analysis revealed that the expression levels of whi genes (whiD, whiG, whiH and whiI) and wbl genes (wblC, wblE, wblH, wblI and wblK) were repressed by different degrees, suggesting an intertwined regulation mechanism of wblAso in morphological differentiation and secondary metabolism of S. somaliensis SCSIO ZH66. Conclusions: wblA orthologues would be effective targets for activation of cryptic gene clusters in marine-derived Streptomyces strains, notwithstanding the regulation mechanisms might be varied in different strains. Moreover, the availability of the vio gene cluster has enriched the diversity of type III PKSs, providing new opportunities to expand the chemical space of polyketides through biosynthetic engineering. [ABSTRACT FROM AUTHOR]

On the basis of the social constructivist theory of emotion, we examined the relationship between employees' emotional creativity and innovative performance in the Chinese business environment, as well as the mediating or moderating roles of intrinsic motivation and supervisors' support for employee creativity in this relationship. Participants were 546 supervisor--subordinate dyads employed at 18 enterprises in the areas of Changsha, Guangzhou, Nanjing, Hangzhou, and Shanghai in China. We performed factor analysis, correlation analysis, and regression analysis of the collected data, and found that employees' emotional creativity had significant effects on their innovative performance, and that their intrinsic motivation played a mediating role in the relationship between emotional creativity and innovative performance. We also found that the supervisors' support for employee creativity positively moderated the relationship between emotional creativity and intrinsic motivation. In addition, the supervisors' support for creativity acted as a mediated moderator of the relationship between employees' emotional creativity and innovative performance. [ABSTRACT FROM AUTHOR]

Background: Marine microorganisms are an important source of new drug leads. However, the discovery and sustainable production of these compounds are often hampered due to the unavailable expression of cryptic biosynthetic gene clusters or limited titer. Ribosome engineering and response surface methodology (RSM) integrated strategy was developed in this study to activate cryptic gene cluster in the deepsea-derived Streptomyces somaliensis SCSIO ZH66, and subsequently isolation, structural analysis, and the yield enhancement of the activated compound, anticancer drug lead Fredericamycin A (FDM A), were performed. Results: In order to discover novel natural products from marine Streptomyces strains by genome mining strategy, the deepsea-derived S. somaliensis SCSIO ZH66 was subject to ribosome engineering to activate the expression of cryptic gene clusters. A resistant strain ZH66-RIF1 was thereby obtained with 300 μg/mL rifampicin, which accumulated a brown pigment with cytotoxicity on MS plate while absent in the wild type strain. After screening of fermentation conditions, the compound with pigment was purified and identified to be FDM A, indicating that the activation of a cryptic FDM A biosynthetic gene cluster was taken place in strain ZH66-RIF1, and then it was identified to be ascribed to the mutation of R444H in the β subunit of RNA polymerase. To further improve the yield efficiently, nine fermentation medium components were examined for their significance on FDM A production by Plackett-Burman design and Box-Behnken design. The optimum medium composition was achieved by RSM strategy, under which the titer of FDM A reached 679.5 ± 15.8 mg/L after 7 days of fermentation, representing a 3-fold increase compared to the original medium. In terms of short fermentation time and low-cost fermentation medium, strain ZH66-RIF1 would be an ideal alternative source for FDM A production. Conclusions: Our results would hasten the efforts for further development of FDM A as a drug candidate. Moreover, this ribosome engineering and RSM integrated methodology is effective, fast and efficient; it would be applicable to genome mining for novel natural products from other strains. [ABSTRACT FROM AUTHOR]

Transparent conductive Dy-doped zinc oxide thin films have been deposited on glass substrates by pulsed laser deposition technique. The effects of post-deposition annealing treatment on structural, electrical and optical properties of the ZnO : (Dy) thin films were investigated. The films show high transparency and conductivity. Van der Pauw measurements reveal that the films are n-type degenerate semiconductors. The electrical resistivity of the films deposited at 300 °C is 2.74 × 10[?]4 O cm with a carrier density of 9.33 × 1020 cm[?]3 and a Hall mobility of 24.48 cm2 V[?]1 s[?]1. The resistivity can be further reduced to as low as 2.12 × 10[?]4 O cm by post-deposition annealing at 420 °C for 2 h in nitrogen. Post-annealing increased the grain size and surface roughness of the films. The average transmission of the ZnO : (Dy) films (with a thickness about 529 nm) in the visible range is above 80%. The optical direct band gap value of the films is about 3.7 eV, which is slightly dependent on the annealing treatment in nitrogen. [ABSTRACT FROM AUTHOR]

Objectives: To explore the immediate and retention effect of real-time tibial acceleration feedback on running biomechanics during gait retraining. Methods: Five electronic databases were searched to identify relevant studies published before May 2022. The included studies were evaluated for methodological quality and bias risk, and data were extracted. A meta-analysis was conducted on the primary outcomes, including peak tibial acceleration (PTA) and vertical ground reaction force. Subgroup analysis was performed by gender, feedback criterion, mode, dosage, fading, retention period, and running environment to evaluate the source of heterogeneity. Qualitative analysis was performed to describe other variables. Results: Fourteen studies (174 participants) were eligible. Meta-analysis showed that real-time tibial acceleration feedback reduced PTA (P < .01, P < .01), vertical impact peak (P = .004, P < .01), vertical average loading rate (P < .01, P < .01), and vertical instantaneous loading rate (P < .01, P < .01) after feedback and during retention period (5 min-12 mo). Subgroup analysis showed that the immediate effect of vertical impact peak was more noticeable with mixed gender (P = .005) and fading feedback (P = .005) conditions, and the retention effect of PTA was more noticeable with high feedback dosage (P < .01) and fading feedback (P < .01) conditions. Conclusions: Real-time tibial acceleration feedback can reduce PTA and vertical ground reaction force during gait retraining, and for periods of 5 minutes to 12 months when the feedback is removed. [ABSTRACT FROM AUTHOR]

Large scaled projects are conducted in South Yellow Sea in recent years. Topographic effect and tidal current are key issues to the coastal engineering and the ocean engineering. In this study, field surveys were conducted to investigate the tidal level, current velocity, and current direction in South Yellow Sea. A numerical model was developed to simulate the radial current field based on the field data. To investigate the mechanism of the radial current field, the actual topography and a smoothed topography were applied in the numerical model, respectively. Results show that, the current field appeares radial because of the tidal system rather than the submarine topography. Local topography centralized the radiation centre and shifted the high-velocity zones. The actual topographic effect is proposed, and results show that local topography increases the flood tide velocity and decreases the ebb tide velocity. Lagrangian residual currents are calculated to illustrate possible sediment sources and transport routes. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is a common malignant tumor, characterized by unlimited proliferation of abnormal plasmocytes in bone marrow. Considering the biological function of B-Lymphocyte stimulator (BLyS) and its receptors in B cell, we examined BLyS and its receptors expression in MM cells. Our studies confirmed that BLyS and its receptors are expressed in MM cells, including KM3, CZ-1, and primary MM cells, playing an important role in the survival and proliferation of MM cells. Additionally, we provide evidence that BLyS protein is located in the MM cell plasma membrane. We also found that IFN-γ and IL-6 can induce BLyS expression on MM cells, while after the treatment of BAY11-7082, an IkB-α phosphorylation inhibitor, IFN-γ induced up regulation of BLyS was completely inhibited, suggesting that nuclear factor κB (NF-κB) might be involved in the mechanism of the regulation of BLyS levels in response to cytokines. Finally, linear correlation analysis of the Lactate Dehydrogenase concentration and beta 2-microglobulin level with BLyS, and expressions of BLyS mRNA in MM patients revealed a significant correlation between them ( P < 0.01 in all case), showing that BLyS could be a biomarker for the diagnosis and treatment of MM. [ABSTRACT FROM AUTHOR]

Organocatalytic direct anti-selective Mannich reactions of O-TBS-hydroxyacetone with various N-tosylimines derived from aromatic aldehydes in the presence of L-threonine-derived catalyst afforded 1,2-amino alcohols in good yields and with enantioselectivities of 99% in almost all cases. [ABSTRACT FROM AUTHOR]