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We report a phase-shifting method based on a pinhole point diffraction interferometer. Using the random two-frame phase-shifting algorithm, the piezo electric transducer (PZT) drives the pinhole moving a certain step length along the axis of the tested aspheric mirror. In each step, the CCD collects an interferogram. Then two interferograms are processed by the phase-shifting algorithm. After that, we can acquire the phase map of the interferograms. This technique has great potential for increasing the measuring aperture of the aspheric mirror in the pinhole point diffraction interferometer (PPDI) under the premise of keeping the advantages of PPDI of which the optic devices, as well as error sources, are few behind the substrate.
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In three dimensional profilometry, phase retrieval technique plays a key role in signal processing stage. Fringe images need to be transformed into phase information to obtain the measurement result. In this paper, a new phase retrieval method based on deep learning technique is proposed for interferometry. Different from conventional multi-step phase shift methods, phase information can be extracted from only a single frame of an interferogram by this method. Here, the phase retrieval task is regarded as a regression problem and a hypercolumns convolutional neural network is constructed to solve it. Firstly, functions and each component of the network model are introduced in details; Then, four different mathematical functions are adopted to generate the training dataset; training and validation strategies are also designed subsequently; Finally, optimization processing is performed to eliminate local data defects in initial results with the help of polynomial fitting. In addition, hardware platform based on point diffraction interferometer is fabricated to support this method. Concluded from the experiment section, the proposed method possesses a desirable performance in terms of phase retrieval, denoising and time efficiency.
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Clostridium sp. strain CT7 is a new emerging microbial cell factory with high butanol production ratio owing to its non-traditional butanol fermentation mode with uncoupled acetone and 1,3-propanediol formation. Significant changes of metabolic products profile were shown in glycerol- and glucose-fed strain CT7, especially higher butanol and lower volatile fatty acids (VFAs) production occurred from glycerol-fed one. However, the mechanism of this interesting phenomenon was still unclear. To better elaborate the bacterial response towards glycerol and glucose, the quantitative proteomic analysis through iTRAQ strategy was performed to reveal the regulated proteomic expression levels under different substrates. Proteomics data showed that proteomic expression levels related with carbon metabolism and solvent generation under glycerol media were highly increased. In addition, the up-regulation of hydrogenases, ferredoxins and electron-transferring proteins may attribute to the internal redox balance, while the earlier triggered sporulation response in glycerol-fed media may be associated with the higher butanol production. This study will pave the way for metabolic engineering of other industrial microorganisms to obtain efficient butanol production from glycerol.
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Proteínas de Bactérias/metabolismo , Butanóis/metabolismo , Clostridium/crescimento & desenvolvimento , Clostridium/metabolismo , Glucose/metabolismo , Glicerol/metabolismo , Proteoma/metabolismo , Fermentação , Proteoma/análiseRESUMO
Succinic acid is a valuable bulk chemical, which has been extensively applied in food, medicine, surfactants and biodegradable plastics industries. As a substitute for chemical raw material, bio-based succinic acid production has received increasing attention due to the depletion of fossil fuels and environmental issues. Meanwhile, the effective bioconversion of lignocellulosic biomass has always been a hot spot of interest owning to the advantages of low expense, abundance and renewability. Consolidated bioprocessing (CBP) is considered to be an alternative approach with outstanding potential, as CBP can not only improve the product yield and productivity, but also reduce the equipment and operating costs. In addition, the current emerging microbial co-cultivation systems provide strong competitiveness for lignocellulose utilization through CBP. This article comprehensively discusses different strategies for the bioconversion of lignocellulose to succinic acid. Based on the principles and technical concepts of CBP, this review focuses on the progress of succinic acid production under different CBP strategies (metabolic engineering based and microbial co-cultivation based). Moreover, the main challenges faced by CBP-based succinic acid fermentation are analyzed, and the future direction of CBP production is prospected.
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Lignina/metabolismo , Engenharia Metabólica/métodos , Ácido Succínico/metabolismo , Biomassa , Técnicas de Cocultura , FermentaçãoRESUMO
Consolidated bioprocessing (CBP) by using microbial consortium was considered as a promising approach to achieve direct biofuel production from lignocellulose. In this study, the interaction mechanism of microbial consortium consisting of Thermoanaerobacterium thermosaccharolyticum M5 and Clostridium acetobutylicum NJ4 was analyzed, which could achieve efficient butanol production from xylan through CBP. Strain M5 possesses efficient xylan degradation capability, as 19.73 g/L of xylose was accumulated within 50 hr. The efficient xylose utilization capability of partner strain NJ4 could relieve the substrate inhibition to hydrolytic enzymes of xylanase and xylosidase secreted by strain M5. In addition, the earlier solventogenesis of strain NJ4 was observed due to the existence of butyrate generated by strain M5. The mutual interaction of these two strains finally gave 13.28 g/L of butanol from 70 g/L of xylan after process optimization, representing a relatively high butanol production from hemicellulose. Moreover, 7.61 g/L of butanol was generated from untreated corncob via CBP. This successfully constructed microbial consortium exhibits efficient cooperation performance on butanol production from lignocellulose, which could provide a platform for the emerging butanol production from lignocellulose.
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Biomassa , Butanóis/metabolismo , Clostridium acetobutylicum/metabolismo , Lignina/metabolismo , Thermoanaerobacterium/metabolismo , Bioengenharia , Biotecnologia , Consórcios Microbianos , Xilanos/metabolismoRESUMO
Biobutanol can be indigenously synthesized by solventogenic Clostridium species; however, these microorganisms possess inferior capability of utilizing abundant and renewable organic wastes, such as starch, lignocellulose, and even syngas. The common strategy to achieve direct butanol production from these organic wastes is through genetic modification of wild-type strains. However, due to the complex of butanol synthetic and hydrolytic enzymes expression systems, the recombinants show unsatisfactory results. Recently, setting up microbial co-culturing systems became more attractive, as they could not only perform more complicated tasks, but also endure changeable environments. Hence, this mini-review comprehensively summarized the state-of-the-art biobutanol production from different substrates by using microbial co-culturing systems. Furthermore, strategies regarding establishment principles of microbial co-culturing systems were also analyzed and compared.
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Butanóis/metabolismo , Técnicas de Cocultura , Fermentação , Resíduos Industriais , Lignina/metabolismo , Amido/metabolismo , 1-Butanol/metabolismo , HidróliseRESUMO
A novel butanogenic Clostridium sp. NJ4 was successfully isolated and characterized, which could directly produce relatively high titer of butanol from inulin through consolidated bioprocessing (CBP). The assembled draft genome of strain NJ4 is 4.09 Mp, containing 3891 encoded protein sequences with G+C content of 30.73%. Among these annotated genes, a levanase, a hypothetical inulinase, and two bifunctional alcohol/aldehyde dehydrogenases (AdhE) were found to play key roles in the achievement of ABE production from inulin through CBP.
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Reatores Biológicos/microbiologia , Butanóis/metabolismo , Clostridium/genética , Genoma Bacteriano , Inulina/metabolismo , Álcool Desidrogenase/genética , Aldeído Desidrogenase/genética , Sequência de Bases , Vias Biossintéticas , Clostridium/metabolismo , Biologia Computacional , DNA Bacteriano/genética , Bases de Dados Genéticas , Glicosídeo Hidrolases/genética , Glicosídeo Hidrolases/metabolismo , RNA Ribossômico 16S/genéticaRESUMO
While NMR and IR spectroscopic signatures and structural characteristics of low-barrier hydrogen bond (LBHB) formation are well documented in the literature, direct measurement of the LBHB energy is difficult. Here, we show that solid-state 17 Oâ NMR spectroscopy can provide unique information about the energy required to break a LBHB. Our solid-state 17 Oâ NMR data show that the HB enthalpy of the Oâ â â Hâ â â N LBHB formed in crystalline nicotinic acid is only 7.7±0.5â kcal mol-1 , suggesting that not all LBHBs are particularly strong.
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Electrochemiluminescence (ECL) of a hybrid system consisting of PbS nanocrystals (NCs) and a BODIPY dye (BDY) capping ligand was discovered to produce highly efficient dual emissions with tri-n-propylamine as a coreactant. By means of spooling ECL spectroscopy, the strong dual ECL emission peaks of 984 and 680 nm were attributed to the PbS and BDY moieties, respectively, and found to be simultaneous during the light evolution and devolution. The ECL of the PbS was enhanced via NC collisions with the electrode and reached an efficiency of 96% relative to that of Ru(bpy)3(2+), which is the highest among the semiconductor NCs.
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We report a solid-state NMR study of (17)O-labeled hydroxylammonium chloride ([H(17)O-NH3]Cl) and sodium trioxodinitrate monohydrate (Na2[(17)ONNO2]·H2O, Angeli's salt). The common feature in these two compounds is that they both contain oxygen atoms that are singly bonded to nitrogen. For this class of oxygen-containing functional groups, there is very limited solid-state (17)O NMR data in the literature. In this work, we experimentally measured the (17)O chemical shift and quadrupolar coupling tensors. With the aid of plane-wave DFT computation, the (17)O NMR tensor orientations were determined in the molecular frame of reference. We found that the characteristic feature of an O-N single bond is that the (17)O nucleus exhibits a large quadrupolar coupling constant (13-15 MHz) but a rather small chemical shift anisotropy (100-250 ppm), in sharp contrast with the nitroso (OâN) functional group for which both quantities are very large (e.g., 16 MHz and 3000 ppm, respectively).
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Hidroxilamina/química , Nitritos/química , Anisotropia , Peróxido de Hidrogênio/química , Espectroscopia de Ressonância Magnética , Modelos Químicos , Nitrogênio/química , Oxigênio/química , Isótopos de Oxigênio/químicaRESUMO
Boranes with the general formula of HBR2 have been found to undergo a facile 1,1-hydroboration reaction with pyrido[1,2-a]isoindole (A), resulting in insertion of a BR2 unit into a CN bond and the formation of a variety of BN heterocycles. Investigation on the thermal reactivity of the BN heterocycles revealed that these molecules have two distinct and competitive thermal elimination pathways: HBR2 elimination (or retro-hydroboration) versus RH elimination, depending on the R group on the B atom and the chelate backbone. Mechanistic aspects of these highly unusual reactions have been established from both experimental and computational evidence. Adduct formation between HBR2 and A was found to be the key intermediate in 1,1-hydroboration of A.
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New BN-heterocyclic compounds have been found to undergo double arene photoelimination, forming rare yellow fluorescent BN-pyrenes that contain two BN units. Most significant is the discovery that the double arene elimination can also be driven by excitons generated electrically within electroluminescent (EL) devices, enabling the in situ solid-state conversion of BN-heterocycles to BN-pyrenes and the use of BN-pyrenes as emitters for EL devices. The inâ situ exciton-driven elimination (EDE) phenomenon has also been observed for other BN-heterocycles.
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The effects of inoculating lactic acid bacteria (LAB), specifically Lactiplantibacillus plantarum, Latilactobacillus sakei, Latilactobacillus curvatus, and Weissella hellenica on the flavor, texture, and color formation of dry sausages in which NaCl was partially substituted by 40% KCl, were explored in this study. It was found that LAB inoculation increased the presence of ketones, alcohols, acids, esters, and terpenes. It also reduced the pH, moisture, protein, and fat content, improving the b*-value, flavor, and texture of the sausages. Notably, L. sakei inoculation showed the most significant improvement in dry sausages with NaCl substitutes, especially on the reduction of bitterness. Meanwhile, there was a close positive correlation between the LAB count with the alcohols and esters formation of dry sausage with NaCl substitution (p < 0.05). These findings offer insight into improving the product characteristics of dry sausages using NaCl substitutes.
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Photothermal therapy combined with chemotherapy has shown great promise in the treatment of cancer. In this synergistic system, a safe, stable, and efficient photothermal agent is desired. Herein, an effective photothermal agent, carbon quantum dots (CQDs), was initially synthesized and then rationally constructed a folic acid (FA)-targeted photothermal multifunctional nanoplatform by encapsulating CQDs and the anticancer drug doxorubicin (DOX) in the liposomes. Indocyanine green (ICG), a near infrared (NIR) photothermal agent, approved by the U.S. Food and Drug Administration, was embedded in the bilayer membrane to further enhance the photothermal effects and facilitate the rapid cleavage of liposomes for drug release. Triggered by the NIR laser, this engineered photothermal multifunctional nanoplatform, not only exhibited an excellent performance with the photothermal conversion efficiency of up to 47.14%, but also achieved controlled release of the payloads. In vitro, and in vivo experiments demonstrated that the photothermal multifunctional nanoplatform had excellent biocompatibility, enhanced tumor-specific targeting, stimuli-responsive drug release, effective cancer cell killing and tumor suppression through multi-modal synergistic therapy. The successful construction of this NIR light-triggered targeted photothermal multifunctional nanoplatform will provide a promising strategy for the design and development of synergistic chemo-photothermal combination therapy and improve the therapeutic efficacy of cancer treatment.
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The existence of the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) greatly limits the application of chemotherapy in glioma. To address this challenge, an optimal drug delivery system must efficiently cross the BBB/BBTB and specifically deliver therapeutic drugs into glioma cells while minimizing systemic toxicity. Here we demonstrated that glucose-regulated protein 78 (GRP78) and dopamine receptor D2 were highly expressed in patient-derived glioma tissues, and dopamine receptors were highly expressed on the BBB. Subsequently, we synthesized a novel "Y"-shaped peptide and compared the effects of different linkers on the receptor affinity and targeting ability of the peptide. A peptide-drug conjugate (pHA-AOHX-VAP-doxorubicin conjugate, pHA-AOHX-VAP-DOX) with a better affinity for glioma cells and higher solubility was derived for glioma treatment. pHA-AOHX-VAP-DOX could cross both BBB and BBTB via dopamine receptor and GRP78 receptor, and finally target glioma cells, significantly prolonging the survival time of nude mice bearing intracranial glioma. Furthermore, pHA-AOHX-VAP-DOX significantly reduced the toxicity of DOX and increased the maximum tolerated dose (MTD). Collectively, this work paves a new avenue for overcoming multiple barriers and effectively delivering chemotherapeutic agents to glioma cells while providing key evidence to identify potential receptors for glioma-targeted drug delivery.
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Barreira Hematoencefálica , Neoplasias Encefálicas , Doxorrubicina , Sistemas de Liberação de Medicamentos , Chaperona BiP do Retículo Endoplasmático , Glioma , Camundongos Nus , Peptídeos , Animais , Glioma/tratamento farmacológico , Glioma/metabolismo , Glioma/patologia , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Doxorrubicina/farmacocinética , Humanos , Linhagem Celular Tumoral , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Peptídeos/química , Peptídeos/administração & dosagem , Barreira Hematoencefálica/metabolismo , Proteínas de Choque Térmico/metabolismo , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/uso terapêutico , Camundongos Endogâmicos BALB C , Receptores de Dopamina D2/metabolismo , Camundongos , MasculinoRESUMO
To examine the impact of metal moieties that have different triplet energies on the photoisomerization of B(ppy)Mes2 compounds (ppy = 2-phenyl pyridine, Mes = mesityl), three metal-functionalized B(ppy)Mes2 compounds, Re-B, Au-B, and Pt-B, have been synthesized and fully characterized. The metal moieties in these three compounds are Re(CO)3(tert-Bu2 bpy)(C≡C), Au(PPh3)(C≡C), and trans-Pt(PPh3)2(C≡C)2, respectively, which are connected to the ppy chelate through the alkyne linker. Our investigation has established that the Re(I) unit completely quenches the photoisomerization of the boron unit because of a low-lying intraligand charge transfer/MLCT triplet state. The Au(I) unit, albeit with a triplet energy that is much higher than that of B(ppy)Mes2 , upon conjugation with the ppy chelate unit, substantially increases the contribution of the πâπ* transition, localized on the conjugated chelate backbone in the lowest triplet state, thereby leading to a decrease in the photoisomerization quantum efficiency (QE) of the boron chromophore when excited at 365â nm. At higher excitation energies, the photoisomerization QE of Au-B is comparable to that of the silyl-alkyne-functionalized B(ppy)Mes2 (TIPS-B), which was attributable to a triplet-state-sensitization effect by the Au(I) unit. The Pt(II) unit links two B(ppy)Mes2 together in Pt-B, thereby extending the π-conjugation through both chelate backbones and leading to a very low QE of the photoisomerization. In addition, only one boron unit in Pt-B undergoes photoisomerization. The isomerization of the second boron unit is quenched by an intramolecular energy transfer of the excitation energy to the low-energy absorption band of the isomerized boron unit. TD-DFT computations and spectroscopic studies of the three metal-containing boron compounds confirm that the photoisomerization of the B(ppy)Mes2 chromophore proceeds through a triplet photoactive state and that metal units with suitable triplet energies can be used to tune this system.
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Highly fluorescent π-conjugated polycyclic azaborines can be prepared from B,N-heterocyclic compounds with a BR2 -CH2 unit through the elimination of an R-H molecule (see scheme). These clean photoelimination reactions occur both in solution and in polymers doped with the precursors.
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Effective oral therapies are urgently required to treat KRASG12D mutant cancers. Therefore, synthesis and screening were performed for 38 prodrugs of MRTX1133 to identify an oral prodrug of MRTX1133, a KRASG12D mutant protein-specific inhibitor. In vitro and in vivo evaluations revealed prodrug 9 as the first orally available KRASG12D inhibitor. Prodrug 9 exhibited improved pharmacokinetic properties for the parent compound in mice and was efficacious in a KRASG12D mutant xenograft mouse tumor model after oral administration.
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Butyl butyrate has shown wide applications in food, cosmetic, and biofuel sectors. Currently, biosynthesis of butyl butyrate still requires exogenous addition of precursors and lipase, which increases the production cost and limits further large-scale development. In this study, a microbial consortium was first designed to realize direct butyl butyrate production from lignocellulose. The highest butyl butyrate concentration of 34.42 g/L was detected in the solvent phase from 60 g/L glucose using a microbial coculture system composed of Clostridium acetobutylicum NJ4 and Clostridium tyrobutyricum LD with the elimination of butyric acid supplementation. Meanwhile, 13.52 g/L butyl butyrate was synthesized from 60 g/L glucose using a microbial consortium composed of three strains including strain NJ4, strain LD, and Escherichia coli BL21- pET-29a(+)-LE without the addition of any exogenous precursors and lipase. In addition, 2.94 g/L butyl butyrate could be directly produced from 60 g/L microcrystalline cellulose when Trichoderma asperellum was added to the above-mentioned three-strain microbial consortium. This four-strain microbial consortium represents the first study regarding the direct butyl butyrate production from lignocellulose without the supplementation of exogenous precursors and lipase, which may be extended to the biosynthesis of other short-chain esters, such as ethyl acetate and butyl lactate.
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In this study, the bacterial communities and flavor metabolites of 27 traditional naturally fermented sauerkraut samples collected from nine regions of Heilongjiang Province in Northeast China were investigated. The dominant genera were Lactobacillus, Pseudomonas, Alcaligenes, Arcobacter, Pseudarcobacter, Lactococcus, Comamonas, Pediococcus, Prevotella, and Insolitispirillum. A total of 148 volatile compounds were detected in seven categories; esters and acids were the most abundant volatiles. Additionally, the highest content (15.96 mg/g) of lactic acid was detected in YC1. Acetic acid, oleic acid, palmitic acid, elaidic acid, and dehydroacetic acid were the key differential volatile compounds, which may be related to the bacterial communities. Spearman's correlation analysis revealed that Lactococcus and Lactobacillus were significantly positively correlated with flavor metabolites, suggesting that they may play a more significant role in flavor formation. The results of this study can help in the development of better quality of fermented vegetables.