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1.
Artif Intell Med ; 103: 101794, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32143799

RESUMO

BACKGROUND: Deep learning has always been at the forefront of scientific research. It has also been applied to medical research. Hereditary spinocerebellar ataxia (SCA) is characterized by gait abnormalities and is usually evaluated semi-quantitatively by scales. However, more detailed gait characteristics of SCA and related objective methods have not yet been established. Therefore, the purpose of this study was to evaluate the gait characteristics of SCA patients, as well as to analyze the correlation between gait parameters, clinical scales, and imaging on deep learning. METHODS: Twenty SCA patients diagnosed by genetic detection were included in the study. Ten patients who were tested via functional magnetic resonance imaging (fMRI) were included in the SCA imaging subgroup. All SCA patients were evaluated with the International Cooperative Ataxia Rating Scale (ICARS) and Scale for the Assessment and Rating of Ataxia (SARA) clinical scales. The gait control group included 16 healthy subjects, and the imaging control group included seven healthy subjects. Gait data consisting of 10 m of free walking of each individual in the SCA group and the gait control group were detected by wearable gait-detection equipment. Stride length, stride time, velocity, supporting-phase percentage, and swinging-phase percentage were extracted as gait parameters. Cerebellar volume and the midsagittal cerebellar proportion in the posterior fossa (MRVD) were calculated according to MR. RESULTS: There were significant differences in stride length, velocity, supporting-phase percentage, and swinging-phase percentage between the SCA group and the gait control group. The stride length and stride velocity of SCA groups were lower while supporting phase was longer than those of the gait control group. SCA group's velocity was negatively correlated with both the ICARS and SARA scores. The cerebellar volume and MRVD of the SCA imaging subgroup were significantly smaller than those of the imaging control group. MRVD was significantly correlated with ICARS and SARA scores, as well as stride velocity variability. CONCLUSION: SCA gait parameters were characterized by a reduced stride length, slower walking velocity, and longer supporting phase. Additionally, a smaller cerebellar volume correlated with an increased irregularity in gait. Gait characteristics exhibited considerable clinical relevance to hereditary SCA. We conclude that a combination of gait parameters, ataxia scales, and MRVD may represent more objective markers for clinical evaluations of SCA.

2.
J Am Chem Soc ; 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32126754

RESUMO

Because of the typical instability of copper nanoclusters, atom-precise structural elucidation of these nanoclusters has remained elusive. Herein, we report an air- and moisture-stable 23-copper nanocluster (SD/Cu23a or SD/Cu23b) isolated from the reaction of Cu(CF3COO)2, tBuC≡CH, Cu powder, and Ph2SiH2 using a gradient reduction (CuII → CuI → Cu0) strategy (GRS), which is competent for controlling the kinetics of the reduction reaction, thus avoiding formation of pure CuI complexes or large Cu0 nanoparticles. The solid-state structure of the Cu23 nanocluster shows a rare [Cu4]0 tetrahedral kernel surrounded by an outer Cu19 shell, which is protected by tBuC≡C- and CF3COO- ligands. The Cu23nanocluster is a rare four-electron superatom with a 1S21P2 electronic shell closure and can be crystallized in two polymorphs (R3c and R3̅) depending on the solvent used. The crystallization of SD/Cu23a in the R3c space group is mainly governed by van der Waals forces and C-H···F interactions, whereas additional intermolecular C-H···Clchloroform interactions are responsible for the R3̅ space group of SD/Cu23b. This work not only shows the ingenuity of a gradient reduction strategy for the synthesis of copper nanoclusters but also provides a better fundamental understanding of how to produce the polymorphic copper nanoclusters in a precisely tunable fashion.

3.
Chem Biodivers ; 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32134169

RESUMO

Endeavor to discover biorational natural products-based insecticides, two series (30) of novel (9S)-acyloxy derivatives of quinidine and dihydroquinidine were prepared and assessed for their insecticidal activity against Mythimna separata in vivo by the leaf-dipping method at 1 mg/mL. Among all the compounds, especially four derivatives exhibited the best insecticidal activity with final mortality rates of 71.4 %, 75.0 %, 71.4 %, and 75.0 %, respectively. Relatively speaking, 9-hydroxy group is well tolerated, and the results showed that after modification of the hydroxy group with an acyloxy group, the insecticidal activity was significantly increased; the configuration at C8/9 position is important for insecticidal activity, and the (9S)-configuration is optimal; modification of the out-ring double bond is acceptable, and hydrogenation of the double bond enhances insecticidal activity. These preliminary results will pave the way for further modification of quinidine in the development of potential new insecticides.

4.
Chemosphere ; 252: 126495, 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32199160

RESUMO

Straw ash-washing wastewater is generated in the process of straw combustion power generation and potash fertilizer production. The suspended solid particles in straw ash-washing wastewater are hard to be settled down due to its low-density and high pH properties which inhibit the application of traditional chemical flocculants. Bioflocculant has good advantages in flocculating activity, biodegradability and adaptability of wastewater pH fluctuation. However, high production cost limited the large-scale applications of bioflocculant in wastewater treatment. In this study, the feasibility of using feather waste as cheap alternative nitrogen source of alkaliphilic Bacillus agaradhaerens C9 to produce bioflocculant was investigated. The results showed that strain C9 could simultaneously produce keratinase and bioflocculant, and thereby producing bioflocculant (named as BFF) using feather waste as cheap nitrogen source. The optimal fermentation conditions for enzymatic hydrolysis of feather waste and BFF production was 40 g/L feather wastes, 16 g/L glucose, 37 °C and pH 9.5, and the highest yield of 2.5 g/L was obtained. Moreover, BFF was used to flocculate straw ash-washing wastewater which exhibits low-density and high pH properties, and the highest flocculating rate of 93.1% was achieved when 6.0 mg/L BFF was added. This study reported for the first time that feather waste was used as inexpensive alternative nitrogen source for producing bioflocculant which could treat straw ash-washing wastewater, thereby promoting the resourceful utilization of feather waste and the reuse of straw ash-washing wastewater.

5.
Appl Microbiol Biotechnol ; 104(7): 3025-3036, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32009202

RESUMO

The widespread use of caffeine in food and drug industries has caused great environmental pollution. Herein, an efficient caffeine-degrading strain Paraburkholderia caffeinilytica CF1 isolated from a tea garden in China can utilize caffeine as its sole carbon and nitrogen source. Combination of chromatographic and spectrophotometric techniques confirmed that strain CF1 adopts N-demethylation pathway for caffeine degradation. Whole genome sequencing of strain CF1 reveals that it has two chromosomes with sizes 3.62 Mb and 4.53 Mb, and a 174-kb mega-plasmid. The plasmid P1 specifically harbors the genes essential for caffeine metabolism. By analyzing the sequence alignment and quantitative real-time PCR data, the redundant gene cluster of caffeine degradation was elucidated. Genes related to catalyzing the N1-demethylation of caffeine to theobromine, the first step of caffeine degradation were heterologously expressed, and methylxanthine N1-demethylase was purified and characterized. Above all, this study systematically unravels the molecular mechanism of caffeine degradation by Paraburkholderia. KEY POINTS: • Caffeine degradation cluster in Paraburkholderia caffeinilytica CF1 was located in mega-plasmid P1. • The whole genome and the caffeine degrading pathway of P. caffeinilytica CF1 were sequenced and elucidated, respectively. • This study succeeded in heterologous expression of methylxanthine N1-demethylase (CdnA) and Rieske oxygenase reductase (CdnD) and illuminated the roles of CdnA and CdnD in caffeine degradation of P. caffeinilytica CF1.

6.
J Am Chem Soc ; 142(10): 4732-4738, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32058715

RESUMO

The continuous variation of the lattice metric in metal-organic frameworks (MOFs) allows precise control over their chemical and physical properties. This has been realized herein by a series of mixed-linker and Zr6-cluster-based MOFs, namely, continuously variable MOFs (CVMOFs). Similar to the substitutional solid solutions, organic linkers with different lengths and various ratios were homogeneously incorporated into a framework rather than being allowed to form separate phases or domains, which was manifested by single-crystal X-ray diffraction, powder X-ray diffraction, fluorescence quenching experiments, and molecular simulations. The unit cell dimension, surface area, and pore size of CVMOFs were precisely controlled by adopting different linker sets and linker ratios. We demonstrate that CVMOFs allow the continuous and fine tailoring of cell-edge lengths from 17.83 to 32.63 Å, Brunauer-Emmett-Teller (BET) surface areas from 585 to 3791 m2g-1, and pore sizes up to 15.9 Å. Furthermore, this synthetic strategy can be applied to other MOF systems with various metal nodes thus allowing for a variety of CVMOFs with unprecedented tunability.

7.
Inorg Chem ; 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32077693

RESUMO

Six novel copper(I) cluster-based coordination polymers (CPs) [Cu9(pzt)7Cl2]n (1), [Cu2(pzt)Cl]n (2), [Cu4(pzt)3Br]n (3), [Cu(pzt)]n (4), [Cu4(pzt)3I]n (5), and [Cu7(pzt)6I]n (6) were solvothermally synthesized using Hpzt (Hpzt = pyrazine-2-thiol) ligand and well-characterized by elemental analysis, infrared (IR) spectroscopy, powder X-ray diffraction (PXRD), and single-crystal X-ray diffraction (SCXRD). Six CPs exhibit either 2D (4 and 6) or 3D (1-3, and 5) network based on diverse multinuclear {CuxSy} clusters. The structural evolutions of 1-6 are greatly influenced by types of metal halides and the ligand-to-metal molar ratio used in the reaction. Among them, compound 1 displays interesting temperature-dependent photoluminescence arising from triplet cluster-centered (3CC) excited state from the cluster metal core. Compounds 1-6 also exhibit photocurrent responses upon visible-light illumination (λ = 420 nm) in the order 6 > 5 > 3 > 1 > 4 > 2. This work not only shows the structural diversity of {CuxSy} clusters-based CPs but also provides an interesting insight into structural modulation using crystal engineering concept.

8.
Br J Pharmacol ; 2020 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-32037512

RESUMO

BACKGROUND AND PURPOSE: Non-alcoholic fatty liver disease (NAFLD) is a worldwide public health problem with no established pharmacological therapy. Here, we explored the potential benefit of P7C3-A20, a novel aminopropyl carbazole compound with neuroprotective activity, in a NAFLD model, induced in mice by a high-fat diet (HFD). EXPERIMENTAL APPROACH: C57BL/6J mice were given a HFD (42% fat content) for 16 weeks to induce NAFLD. P7C3-A20 (20 mg·kg-1 ·day-1 ) was given by gavage for 2 weeks. Indirect calorimetry, histological analysis, immunoblotting, immunohistochemistry, and biomedical examinations were performed. Gut microbiota were determined using a 16S ribosomal RNA sequencing analysis. KEY RESULTS: P7C3-A20 treatment reduced body weight gain/adiposity, improved insulin resistance, promoted energy expenditure (O2 consumption/CO2 production), inhibited lipid oxidation, suppressed hepatic inflammation (Kupffer cell number and pro-inflammatory factors), decreased necroptosis/apoptosis (receptor-interacting protein kinase 3, cleaved caspase-3, and TUNEL), and alleviated liver fibrosis and injury. Mechanistically, P7C3-A20 stimulated FGF21 and FGF1 via activating liver kinase B1 (LKB1) and AMP-activated protein kinase (AMPK), which further resulted in a reduced nuclear translocation of CREB-regulated transcription coactivator 2 (CRTC2). In AMPKα2 knockout mice, the protection of P7C3-A20 against HFD-induced metabolism abnormalities and fat accumulation, as well as the elevation of blood FGF21 and FGF1, was abolished. P7C3-A20 increased the gut microbiota species richness. Moreover, it enhanced the proportions of Akkermansia, Lactobacillus, and Prevotellaceae, while reducing the proportions of Enterobacteriaceae, Escherichia, and Parasutterella. CONCLUSIONS AND IMPLICATIONS: P7C3-A20 increased levels of NAD+ and alleviated NAFLD through stimulating FGF21 and FGF1 in an LKB1/AMPK/CRTC2-dependent manner and shaping gut microbiota.

9.
J Colloid Interface Sci ; 567: 235-242, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32062084

RESUMO

Metal nanoclusters (NCs) as a new type of fluorescent material have attracted great interest due to their unique electronic structure and outstanding optical properties. However, limited success has been achieved in the preparation of water-soluble NCs with high luminous intensity. In this article, the significant luminescence properties of 4-mercaptobenzoic acid (H2mba)-capped Ag NCs induced by hydrochloric acid (HCl) through self-assembly strategies were reported and the water-soluble protonated silver nanoclusters (Ag-H-NCs) can be obtained. The original non-luminescent Ag NCs exhibit stable and bright luminescence resulting from aggregation-induced emission (AIE) by forming an ordered nanorod structure after assembly. Optical analysis allows for the establishment of relationships between ordered alignment and emission of Ag NCs components and it can be concluded that the ordered nanostructures are constructed by non-covalent interaction (hydrogen bond, π-π stacking, etc.) which effectively inhibits the intramolecular vibration and rotation of the ligand, thereby increasing the emission intensity of Ag NCs. Due to the outstanding optical behavior of the aqueous solution of Ag-H-NCs, it can be used as a rewritable fluorescent platform and a white light emitting diode (LED). The pH-guided strategy enriches the supramolecular self-assembly of novel noble metal NCs, which makes them a good candidate for optical materials.

10.
J Asian Nat Prod Res ; : 1-12, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32009450

RESUMO

Three series of sulfonate derivatives of paeonol were synthesized and screened in vitro for their anti-oomycete activity against P. capsici, respectively. Among all the compounds, 4m displayed the best promising and pronounced anti-oomycete activity against P. capsici than zoxamide, with the EC50 values of 24.51 and 26.87 mg/L, respectively. The results show that acetyl and 4-OCH3 are two necessary groups. The existence of these two sites is closely related to the anti-oomycete activity. Relatively speaking, hydroxyl group is well tolerated, and the results showed that after modification of hydroxyl group with sulfonyl, the anti-oomycete activity was significantly increased.[Formula: see text].

11.
J Asian Nat Prod Res ; : 1-13, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32091234

RESUMO

Endeavor to discover biorational natural products-based insecticides, two series (27) of novel 9R/S-acyloxy derivatives of cinchonidine and cinchonine were prepared and assessed for their insecticidal activity against Mythimna separata in vivo by the leaf-dipping method at 1 mg/mL. Among all the compounds, especially derivatives 6l and 6o exhibited the best insecticidal activity with final mortality rates of 75.0% and 71.4%, respectively. Overall, a free 9-hydroxyl group is not a prerequisite for insecticidal activity and C9-substitution is well tolerated; the configuration of C8/9 position is important for insecticidal activity, and 9S-configuration is optimal; 6'-OCH3 moiety is not necessary, removal of it is also acceptable.

12.
Inorg Chem ; 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32073840

RESUMO

Most of polyoxometallates (POMs) templated silver nanoclusters recorded so far are polyoxomolybdates and polyoxotungstates; however, as congeneric polyoxochromates, they are rarely observed in silver nanoclusters. Herein, a high-nuclearity polyoxochromate, (CrIII4CrVI8O36)12-, is uncovered in a novel silver nanocluster (SD/Ag56a) as an anion template. The mixed-valent (CrIII4CrVI8O36)12- consists of four edge-sharing CrIIIO6 octahedra and eight CrVIO4 tetrahedra, which are fused together by sharing one or two vertexes. The (CrIII4CrVI8O36)12- is the by far highest nuclearity polyoxochromate and is trapped by outer Ag56 bracelet-like shell coprotected by quaternary ligands including iPrS-, NapCOO- (2-naphthalenecarboxylate), CF3COO-, and CH3CN. The antiferromagnetic property and solution behavior of SD/Ag56a are discussed in detail.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31958039

RESUMO

BACKGROUND: It is one of the effective ways for pesticide innovation to develop new insecticides from natural products as lead compounds. Quinine, the main alkaloids in the bark of cinchona tree as well as in plants in the same genus, is recognized as a safe and potent botanical insecticide to many insects. The structural modification of quinine into 9R-acyloxyquinine derivatives is a potential approach for the development of novel insecticides, which showed more toxicity than quinine. However, there are no reports on the insecticidal activity of 9R-acyloxyquinine derivatives to control Mythimna separata. RESULTS: Endeavor to discover biorational natural products-based insecticides, 20 novel 9R-acyloxyquinine derivatives were prepared and assessed for their insecticidal activity against Mythimna separata in vivo by the leaf-dipping method at 1 mg/mL. Among all the compounds, especially derivatives 5i, 5k, and 5t exhibited the best insecticidal activity with final mortality rates of 50.0%, 57.1%, and 53.6%, respectively. CONCLUSION: Overall, a free 9-hydroxyl group is not a prerequisite for insecticidal activity and C9-substitution is well tolerated; modification of out-ring double-bond is acceptable, and hydrogenation of double-bond enhances insecticidal activity; Quinine ring is essential, and open of it is not acceptable. These preliminary results will pave the way for further modification of quinine in the development of potential new insecticides.

14.
Chem Commun (Camb) ; 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31967118

RESUMO

The exquisite combination of hetreometallic [TbIIINiII(COO)3(H2O)] clusters with a designed hexatopic ligand generates one highly robust three-dimensional heterometallic TbIII/NiII-organic framework material {[TbNi(HTDP)(H2O)]·3DMF·2H2O}n (NUC-2; H6TDP = 2,4,6-tri(2,4-dicarboxyphenyl)pyridine). Gas adsorption measurements reveal that the activated NUC-2 exhibits ultrahigh C2H2 adsorption capacity but negligible uptake of C2H4, which is ascribed to its high stability and ultrahigh functional internal surface. Furthermore, dynamic breakthrough experiments confirm that NUC-2 can effectively fulfill the separation of a C2H2/C2H4 (1 : 99) mixture. Such excellent performance makes NUC-2 a promising adsorbent for practical C2H2/C2H4 separation and provides new insights into heterometallic MOFs for gas separation.

15.
Nat Commun ; 11(1): 308, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949133

RESUMO

Thiacalix[4]arenes as a family of promising ligands have been widely used to construct polynuclear metal clusters, but scarcely employed in silver nanoclusters. Herein, an anion-templated Ag88 nanocluster (SD/Ag88a) built from p-tert-butylthiacalix[4]arene (H4TC4A) is reported. Single-crystal X-ray diffraction reveals that C4-symmetric SD/Ag88a resembles a metal-organic super calix comprised of eight TC4A4- as walls and 88 silver atoms as base, which can be deconstructed to eight [CrO4@Ag11(TC4A)(EtS)4(OAc)] secondary building units arranged in an annulus encircling a CrO42- in the center. Local and global anion template effects from chromates are individually manifested in SD/Ag88a. The solution stability and hierarchical assembly mechanism of SD/Ag88a are studied by using electrospray mass spectrometry. The Ag88 nanocluster represents the highest nuclearity metal cluster capped by TC4A4-. This work not only exemplify the specific macrocyclic effects of TC4A4- in the construction of silver nanocluster but also realize the shape heredity of TC4A4- to overall silver super calix.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31985371

RESUMO

BACKGROUND: Plant secondary metabolites play an important role in novel insecticide discovery for their unique sources and potential target sites. Paeonol, the main phenolic components in Moutan Cortex, is recognized as a safe and potent botanical insecticide to many insects. The structural modification of paeonol into phenylsulfonylhydrazone derivatives is a potential approach for the development of novel insecticides, which showed more toxicity than paeonol. However, there are no reports on the insecticidal activity of paeonol-based phenylsulfonylhydrazone derivatives to control Mythimna separata. METHODS: We always endeavor to discover biorational natural products-based insecticides, 12 novel paeonol-based phenylsulfonylhydrazone derivatives have been successfully perpared by structural modification of paeonol, and evaluated the insecticidal activity against M. separata by the leaf-dipping method at the concentration of 1 mg/mL. RESULTS: Insecticidal activity revealed that, out of 12 title compounds, derivatives 5c and 5f displayed the best against M. separate with the FMR both of 53.6% than toosendanin (FMR = 50.0%). CONCLUSION: It suggested that for the paeonol-based phenylsulfonylhydrazone series derivatives, the proper substituent of arylsulfonyl R at the hydroxyl position of paeonol was very important for their insecticidal activity. These preliminary results will pave the way for further modification of paeonol in the development of potential new insecticides.

17.
Ann Plast Surg ; 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31985538

RESUMO

The management of giant neurofibroma is a challenge for clinical surgeons. Abundant malformed vessels exist in the tumor, and life-threatening hemorrhage can occur during operation. Moreover, repairing huge defects after radical resection is challenging. Hence, subtotal resection and debulking are more frequently performed than total resection. Although subtotal resection or debulking may reduce morbidity, it inevitably leads to a high rate of recurrence. In addition, subtotal resection or debulking does not decrease surgical risk; on the contrary, when operating on the tumor body, the rate of hemorrhage is much higher in case of subtotal resection and debulking than in radical resection. In this study, 9 patients with giant neurofibroma were retrospectively reviewed. The tumor size ranged from 12 × 9 cm to 60 × 70 cm. Preoperative angiography and magnetic resonance imaging scanning are performed to clarify the tumor features. All patients underwent radical resection, and in-operation blood loss ranged from 300 to 2600 mL. The resection defects were repaired by anterolateral thigh free flap in 2 patients and skin grafts in 7 patients. Partial skin necrosis occurred in 4 patients, and the necrosis area can be repaired with adjacent survived skin by changing the dressing several times. No tumor recurrence was recorded during routine follow-up (range, 12-39 months). The treatment strategy for radical resection of giant neurofibroma proves effective, and the technique of reusing the skin provides sufficient material for covering a large defect without the morbidity associated with a new donor. Thus, tumor removal and wound repair can be accomplished in one stage.

18.
J Plast Surg Hand Surg ; 54(1): 33-39, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31502914

RESUMO

Recessive dystrophic epidermolysis bullosa (RDEB) is a congenital disease caused by a mutation in the COL7A1 gene and frequently results in hand contractures and pseudosyndactyly. Although multiple treatments exist that can improve the hand malformations, there are currently still no radical cures for this disease because of its high recurrence rate. The present study reports our experiences on how to improve hand deformities in 11 RDEB patients with surgical management and postoperative skin dressings. Hand function was substantially improved after complete release of pseudosyndactyly and achievement of favorable digital web spaces. Patients were followed up for two years, and nine of which showed slight decrease in hand function characterized by re-narrowed web spaces, digit adhesion and flexed metacarpophalangeal (MP) and interphalangeal (IP) joints, while the last two patients underwent hand reoperation one year after their initial surgery because of recurrence. In conclusion, our results show that surgical correction followed by skin dressing changes is an effective approach to improving mitten-hand malformations in RDEB patients.

19.
Mol Microbiol ; 113(1): 123-142, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31628680

RESUMO

BldD generally functions as a repressor controlling morphological development of Streptomyces. In this work, evidences that BldD also activates antibiotic production are provided. In Streptomyces roseosporus (which produces daptomycin widely used for treatment of human infections), deletion of bldD notably reduced daptomycin production, but enhanced sporulation. BldD stimulated daptomycin production by directly activating transcription of dpt structural genes and dptR3 (which encodes an indirect activator of daptomycin production), and repressed its own gene. BldD-binding sites on promoter regions of dptE, dptR3, and bldD were all found to contain BldD box-like sequences, facilitating prediction of new BldD targets. Two Streptomyces global regulatory genes, adpA and afsR, were confirmed to be directly activated by BldD. The protein AfsR was shown to act as an activator of daptomycin production, but a repressor of development. BldD directly represses nine key developmental genes. In Streptomyces avermitilis (which produces effective anthelmintic agents avermectins), BldD homolog (BldDsav) directly activates avermectin production through ave structural genes and cluster-situated activator gene aveR. This is the first report that BldD activates antibiotic biosynthesis both directly and via a cascade mechanism. BldD homologs are widely distributed among Streptomyces, our findings suggest that BldD may activate antibiotic production in other Streptomyces species.

20.
Acta Pharmacol Sin ; 41(1): 119-128, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31534201

RESUMO

Inefficient diabetic ulcer healing and scar formation remain a challenge worldwide, owing to a series of disordered and dynamic biological events that occur during the process of healing. A functional wound dressing that is capable of promoting ordered diabetic wound recovery is eagerly anticipated. In this study, we designed a silicone elastomer with embedded 20(S)-protopanaxadiol-loaded nanostructured lipid carriers (PPD-NS) to achieve ordered recovery in scarless diabetic ulcer healing. The nanostructured lipid carriers were prepared through an emulsion evaporation-solidification method and then incorporated into a network of silicone elastomer to form a unique nanostructured lipid carrier-enriched gel formulation. Interestingly, the PPD-NS showed excellent in vitro anti-inflammatory and proangiogenic activity. Moreover, in diabetic mice with full-thickness skin excision wound, treatment with PPD-NS significantly promoted in vivo scarless wound healing through suppressing inflammatory infiltration in the inflammatory phase, promoting angiogenesis during the proliferation phase, and regulating collagen deposition in the remodeling phase. Hence, this study demonstrates that the developed PPD-NS could facilitate ordered diabetic wound recovery via multifunctional improvement during different wound-healing phases. This novel approach could be promising for scarless diabetic wound healing.

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