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Glycerol kinase is the key enzyme in glycerol metabolism, and its catalytic efficiency has an important effect on glycerol utilization. Based on an analysis of the glycerol utilization pathway and regulation mechanism in B. subtilis, we conducted site-directed mutagenesis of the key glycerol kinase gene (glpK) on the chromosome to improve the glycerol utilization efficiency of Bacillus subtilis. Recombinant wild-type Bacillus subtilis glycerol kinase (BsuGlpK

Adaptive laboratory evolution (ALE) is a technique for the selection of strains with better phenotypes by long-term culture under a specific selection pressure or growth environment. Because ALE does not require detailed knowledge of a variety of complex and interactive metabolic networks, and only needs to simulate natural environmental conditions in the laboratory to design a selection pressure, it has the advantages of broad adaptability, strong practicability, and more convenient transformation of strains. In addition, ALE provides a powerful method for studying the evolutionary forces that change the phenotype, performance, and stability of strains, resulting in more productive industrial strains with beneficial mutations. In recent years, ALE has been widely used in the activation of specific microbial metabolic pathways and phenotypic optimization, the efficient utilization of specific substrates, the optimization of tolerance to toxic substance, and the biosynthesis of target products, which is more conducive to the production of industrial strains with excellent phenotypic characteristics. In this paper, typical examples of ALE applications in the development of industrial strains and the research progress of this technology are reviewed, followed by a discussion of its development prospects.

With the rapid progress of advanced manufacturing, three-dimensional metrology techniques that are able to achieve nanometer spatial resolution and to capture fast dynamics are highly desired, for which a snapshot ability and a common-light-path setup are required. Commonly used off-axis holography and phase-shifting interferometry are short in fulfilling those requirements. We studied the suitability and performance of the coherent modulation imaging (CMI) method for metrology applications. Both transparent and reflective samples are measured in visible light experiments. Thanks to its ability to retrieve separate wavefronts at different wavelengths from a single measurement, CMI allows for attaining an enlarged range of measurement free from phase wrapping by utilizing the concept of synthetic wavelength. The CMI method fulfills well the requirements for advanced metrology and can be implemented at any wavelength. We expect it would be a powerful addition to the pool of advanced metrology tools.

Objective Through the preparation of the diabetic mice skin ulcer model, we investigated the effect of Mongolian medicine external ulcer powder (WYK) on the treatment of diabetic skin ulcers and the expression of angiogenesis-related factors such as vascular endothelial growth factor (VEGF) and extracellular regulated protein kinases (ERK). Methods Thirty male clean Kunming mice were randomly divided into normal control group (group C), diabetic control group (group HC), and diabetic topical ulcer powder group (group HW). After successful modeling in the HC group and the HW group, the rats in the HW group were given external ulcer powder, which was applied to the back of the mice once a day. In addition, the rats in group C and group HC were treated with gentamicin injection external application once a day. The mice were sacrificed on the 3rd, the sixth, and the ninth day of dosing, and samples were taken. The adopted methods included protein immunoblotting (western blot) and reverse transcription-polymerase chain reaction (RT-PCR). The expression differences of angiogenesis-related factors such as VEGF and ERK in the repair process were detected. SPSS 13 software was used to analyze the results of angiogenesis-related factors VEGF and ERK. Results Comparison of VEGF and ERK Contents The serum VEGF content of mice in the HC group was significantly lower than that in the C group on days 3, 6, and 9 (p0.05). The VEGF content in the HW group was significantly higher than that in the HC group (p0.05). The content of ERK in serum was basically consistent with that of VEGF. The results of the western blot assay were consistent with those of the RT-PCR assay. Conclusion WYK can effectively promote the healing of skin ulcer wounds in diabetic mice, accelerate the proliferation of granulation tissue, enrich the contents of capillary blood tubes and collagen fibers, and increase the microvascular content. WYK can improve the expression level of VEGF and ERK in the serum of mice and advance the peak value of protein expression.

Overexpression, point mutations or translocations of protein lysine methyltransferase NSD2 was occurred in many types of cancer cells. Therefore, it was recognized as onco-protein and considered as a promising anticancer drug target. NSD2 consists of a SET catalytic domain and two PWWP domains binding to methylated histone proteins. Here, we reported our efforts to develop a series of NSD2-PWWP1 inhibitors, and further structure-based optimization resulted a potent inhibitor 38, which has the high selectivity towards NSD2-PWWP1 domain. The detailed biological evaluation revealed that compound 38 can bind to NSD2-PWWP1 and then affect the expression of genes regulated by NSD2. The current discovery will provide a useful chemical probe to the future research in understanding the specific regulation mode of NSD2 by PWWP1 recognition, and pave the way to develop potential drugs targeting NSD2 protein.

The protein, tripartite motif containing 24 (TRIM24) is a member of the TRIM protein family, and acts as a critical co‐regulator of multiple nuclear receptors. TRIM24 is dysregulated in many cancers, including colorectal carcinoma. However, its biological functions and molecular mechanisms with respect to colorectal carcinoma are still largely unknown. In the current study, we found that TRIM24 promotes YAP signaling for driving cell proliferation in colorectal cancer. TRIM24 was significantly upregulated in colorectal carcinoma, and its expression was negatively correlated with the survival of patients. Depletion of TRIM24 impaired the ability of the cancer cells to proliferate and form colonies. Furthermore, this study also revealed the mechanism underlying the recruitment of TRIM24 by the DANCR/KAT6A complex, which is bound to acetylated lysine 23 of histone H3 (H3K23), resulting in binding to the YAP promoter and activation of YAP transcription that ultimately enhances the proliferation of colorectal cancer cells. Our results revealed a novel mechanism involving TRIM24‐YAP signaling for the regulation of colorectal cancer. We also identified TRIM24 as a potential therapeutic molecule for targeting colorectal cancer., Here, we evaluated TRIM24 expression in colorectal cancer, and revealed a positive correlation between TRIM24 expression level and survival prognosis. TRIM24 promotes cell proliferation via YAP signaling. Finally, potential mechanism of DANCR/KAT6A complex on TRIM24 response was explored.

Introduction: Some experimental research has proved that long-term basketball exercises can effectively improve physical fitness, promote growth and improve motor functions. However, studies exploring the specific effects of this sport on cardiac and cerebral vascularization are still scarce. Objective: We aimed to study, through experimental analysis, if the activities derived from basketball sport can have some influence on cardiac and cerebral vascularization. Methods: Twelve students with no family history of genetic diseases and in good health, who regularly practice amateur basketball, were followed for 8 weeks. Weight, height, body mass index, body fat rate, maximum oxygen consumption, hemoglobin, and indicators of lipid metabolism were analyzed. Results: After long-term basketball exercises, the body fat rate of these college students decreased significantly, and total serum cholesterol and low-density lipoprotein also show significant differences compared with the control group. Conclusion: Through the processing and analysis of the experimental data, it can be concluded that basketball can effectively reduce the human body fat rate, maintain a healthy body shape, and indirectly reduce the risk of cardiovascular and cerebrovascular diseases. Level of evidence II; Therapeutic studies - investigation of treatment results. RESUMO Introdução: Algumas pesquisas experimentais provaram que exercícios de basquetebol a longo prazo podem efetivamente melhorar a aptidão física, promover o crescimento e melhorar as funções motoras. Porém, ainda são escassos os estudos que exploram os efeitos específicos desse esporte na vascularização cardíaca e cerebral. Objetivo: Objetiva-se estudar, através de análise experimental, se as atividades derivadas do esporte basquete podem ter alguma influência sobre a vascularização cardíaca e cerebral. Métodos: Houve acompanhamento por 8 semanas de doze alunos sem histórico familiar com doença genética e em boa saúde com prática regular do basquete de forma amadora. Foram analisados peso, altura, índice de massa corporal, taxa de gordura corporal, consumo máximo de oxigênio, hemoglobina e indicadores de metabolismo lipídico. Resultados: Após exercícios de basquetebol de longa duração, a taxa de gordura corporal destes estudantes universitários diminuiu significativamente, e o colesterol sérico total e a lipoproteína de baixa densidade também apresentam diferenças significativas em comparação com o grupo de controle. Conclusão: Através do processamento e análise dos dados experimentais, pode-se concluir que o basquetebol pode efetivamente reduzir a taxa de gordura do corpo humano, manter uma forma corporal saudável e, indiretamente, reduzir o risco de doenças cardiovasculares e cerebrovasculares. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento. RESUMEN Introducción: Algunas investigaciones experimentales han demostrado que los ejercicios de baloncesto a largo plazo pueden mejorar eficazmente la aptitud física, promover el crecimiento y mejorar las funciones motoras. Sin embargo, los estudios que exploran los efectos específicos de este deporte en la vascularización cardíaca y cerebral son todavía escasos. Objetivo: El propósito de este trabajo es estudiar, mediante un análisis experimental, si las actividades derivadas del deporte del baloncesto pueden tener alguna influencia en la vascularización cardíaca y cerebral. Métodos: Se realizó un seguimiento de 8 semanas a doce estudiantes sin antecedentes familiares de enfermedad genética y en buen estado de salud con práctica regular de baloncesto amateur. Se analizaron el peso, la altura, el índice de masa corporal, el índice de grasa corporal, el consumo máximo de oxígeno, la hemoglobina y los indicadores del metabolismo de los lípidos. Resultados: Después de realizar ejercicios de baloncesto a largo plazo, el índice de grasa corporal de estos estudiantes universitarios disminuyó significativamente, y el colesterol sérico total y la lipoproteína de baja densidad también muestran diferencias significativas en comparación con el grupo de control. Conclusión: Mediante el procesamiento y el análisis de los datos experimentales, se puede concluir que el baloncesto puede reducir eficazmente la tasa de grasa corporal del ser humano, mantener una forma corporal saludable y reducir indirectamente el riesgo de enfermedades cardiovasculares y cerebrovasculares. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Overexpression, point mutations or translocations of protein lysine methyltransferase NSD2 was occurred in many types of cancer cells. Therefore, it was recognized as onco-protein and considered as a promising anticancer drug target. NSD2 consists of a SET catalytic domain and two PWWP domains binding to methylated histone proteins. Here, we reported our efforts to develop a series of NSD2 PWWP1 inhibitors, and further structure-based optimization resulted a potent inhibitor 38, which has the high selectivity towards NSD2 PWWP1 domain. The detailed biological evaluation revealed that compound 38 can bind to NSD2-PWWP1 and then affect the expression of genes regulated by NSD2. We believe that the current discovery will provide a useful chemical probe to the future research in understanding the specific regulation mode of NSD2 by PWWP1 recognition.

Coherent diffraction imaging (CDI) is a rapidly advancing technique, especially for imaging weakly absorptive samples with x-rays or electrons at nano or atomic resolutions. For the study of fast dynamics, single-shot imaging ability is essential. However, reconstructions provided by current single-shot CDI methods are subject to the impairment of illumination artifacts. If one wants to obtain artifact-free object images, flat or well-calibrated illumination would be required. Here, we proposed an extension to coherent modulation imaging (CMI) to realize pure object function retrieval from a single sample measurement. This extension removes the restrictions on the forms of illumination and allows flexibly placing the object between the illumination aperture and the modulator. Our method has been verified in the numerical simulation and visible light experiment, and it could make CMI a practical and powerful microscopy technique.

Anagrus nilaparvatae is an important egg parasitoid wasps of rice pests rice planthopper. Based on the powerful olfactory system of sensing chemical information in nature, A. nilaparvatae shows complicated life activities and behaviors, such as feeding, mating and hosting. In this study, we constructed a full-length transcriptome library and further to identify the characteristics of olfactory binding proteins, the first participant in the olfactory system. Through full-length transcriptome sequencing, splicing, assembly, and data correction by Illumina, we obtained 163.59Mb of transcriptome data and 501,179 items of annotation information, and performed GO functional classification of unigenes of the transcriptome. We analyzed the sequence characteristics of olfactory binding protein genes, and 8 genes (AnilOBP2, AnilOBP9 AnilOBP23, AnilOBP56, AnilOBP83, AnilCSP5, AnilCSP6 and AnilNPC2) were identified. After sequence alignment and conserved domain prediction, the 8 proteins were consistent with the typical characteristics of OBPs, CSPs and NPC2s in insects. The phylogenetic tree analysis showed that the 8 genes share low homology relationship with other species in Hymenopteran. Finally, RT-qPCR was used to analyze the expression responses of the 8 genes in different genders and stimulated by volatiles. The relative expression levels of AnilOBP9, AnilOBP26, AnilOBP83, AnilCSP5 and AnilNPC2 in males were significantly higher than those in female, while the relative expression levels of AnilCSP6 were opposite. The expression levels of AnilOBP9 and AnilCSP6 were significantly altered by the stimulation of β-caryophylene, suggesting the two genes may be related to host searching. In this study, the transcriptome data of parasitoid wasps A. nilaparvatae could provide a reference for the molecular biology research of the parasitoids, and the identification and analysis of olfactory binding proteins not only help us further clarify the physiological characteristics and parasitic mechanism of the parasitoids, but also promote the utilization of natural enemy resources.

The C2-selective C–H alkoxycarbonylation of indoles with alcohols and CO catalyzed by RhCl3·3H2O is disclosed that offers convenient access to diverse indole-2-carboxylic esters. The rhodium-based catalysts outperformed all other precious-metal catalysts investigated. In addition, this protocal was found applicable to the synthesis of pyrrole-2-carboxylic esters, and allowed the C–H alkoxycarbonylation in an intramolecular fashion. Preliminary mechanistic studies indicate that C–H cleavage is not likely involved in the rate-determining step, and a five-membered rhodacycle might be an intermediate involved in the reaction.

A concise and highly stereoselective total synthesis of the Daphniphyllum alkaloids (-)-daphenylline has been accomplished. The synthesis was started from (S)-carvone and proceeded via a stereoselective Mg(ClO4 )2 -catalyzed intramolecular amide addition cyclization, an intramolecular Diels-Alder reaction to construct the ABCD tetracyclic core architecture, and a Robinson annulation coupled with an oxidative aromatization sequence. Finally, the DF ring system was installed through an intramolecular Friedel-Crafts cyclization. The total synthesis of (-)-daphenylline is achieved in 19 steps in the longest reaction sequence and in 7.6 % overall yield.

An efficient general strategy for the synthesis of the Daphniphyllum alkaloids via the rapid construction of the common core intermediate has been estabilshed, based on which a divergent total synthesis of (-)-daphenylline and (-)-himalensine A has respectively been accomplished in 16 and 19 steps. The present work features an enantioselective Mg(ClO 4 ) 2 -catalyzed intramolecular amidocyclization to construct the aza-bridged core structure; a Cu-catalyzed intramolecular cyclopropanation and subsequent phosphine-catalyzed Cope-type rearrangement to furnish the himalensine A scaffold; and a one-pot Diels-Alder/aromatization method to assemble the aromatic skeleton of daphenylline.

In this study, we synthesized bismaleimide into a functionalized double-decker silsesquioxane (DDSQ) cage. This was achieved by hydrosilylation of DDSQ with nadic anhydride (ND), reacting it with excess p-phenylenediamine to obtain DDSQ-ND-NH2, and treating with maleic anhydride (MA), which finally created a DDSQ-BMI cage structure. We observed that the thermal decomposition temperature (Td) and char yield were both increased upon increasing the thermal polymerization temperature, and that these two values were both significantly higher than pure BMI without the DDSQ cage structure since the inorganic DDSQ nanoparticle could strongly enhance the thermal stability based on the nano-reinforcement effect. Based on FTIR, TGA, and DMA analyses, it was found that blending epoxy resin with the DDSQ-BMI cage to form epoxy/DDSQ-BMI hybrids could also enhance the thermal and mechanical properties of epoxy resin due to the organic/inorganic network formation created by the ring-opening polymerization of the epoxy group and the addition polymerization of the BMI group due to the combination of the inorganic DDSQ cage structure and hydrogen bonding effect. The epoxy/DDSQ-BMI = 1/1 hybrid system displayed high Tg value (188 °C), Td value (397 °C), and char yield (40.4 wt%), which was much higher than that of the typical DGEBA type epoxy resin with various organic curing agents.

Space power synthesis technology can obtain up to N2 times jamming power gain. For distributed motion platforms, synchronization is the key factor to achieve efficient space power synthesis. Based on the basic principle of space power synthesis, the signal propagation model of jamming system on distributed motion platforms is established. The influence of time synchronization error, frequency synchronization error and position error on space power synthesis is analyzed, and Monte Carlo simulation tests are carried out. The simulation results show that distributed jamming system based on space power synthesis technology can effectively reduce the detection distance of air defense radar. Increase of platforms quantity and decrease of phase error can provide higher jamming performance.

Coherent modulation imaging (CMI) has been shown to be an effective lensless diffraction approach to imaging general extended samples with fast algorithmic convergence and high robustness to data imperfection. Being a single-shot technique, CMI holds a high potential for imaging dynamics with ultrafast pulses like the ones from free-electron lasers. In the reported work, strong modulators have been suggested for CMI to have the optimal performance, which may be an obstacle for the wide adoption of the method. Here we show that with our improved reconstruction algorithm the requirements on the modulation depth and feature size of a modulator can be relaxed. Furthermore, we demonstrate that when cascade configuration is used, the modulators can be even weaker while providing lower image errors in reconstruction than the case of a single modulator. Detailed numerical studies in both far-field and near-field experiment geometry are given via simulation. A relaxed requirement on modulators in CMI could pave the way for its wide use in biology and materials science.

Coherent modulation imaging (CMI) is an effective lensless diffraction imaging method with fast algorithmic convergence and high robustness to data defects. In the reported algorithms for CMI, one important requirement is that the modulator function need to be known a priori; and an additional step for the modulator characterization is required to be carried out in advance by other methods, such as ptychography, which could be cumbersome in practice. Here, we propose an improved algorithm that allows for the transmission function of a completely unknown modulator to be recovered during the same iterative process of image reconstruction. We have verified the method in both simulations and optical experiments. This improvement would turn CMI into a more practical and standalone technique for broader applications in biology and materials science.

Two new series of transparent polyamide-imides (PAIs) with high modulus and low coefficient of thermal expansion (CTE) were prepared by random or block copolymerization of 4,4′-biphthalic dianhydride (BPDA) and p-phthaloyl chloride (TPC) with 2,2′-bis(trifluoromethyl)benzidine (TFDB). These series of PAIs displayed low CTE of 16–42 ppm/K, good mechanical properties with high tensile modulus ranging from 4.9 to 6.6 GPa, tensile strengths of 112–170 MPa and elongations at break of 2.0–5.4%, as well as high transparency with transmittances at 500 nm (T500nm) of 84–87%, which was greatly affected by the feed ratio of monomer BPDA & TPC, and the block length caused by block polymerization. The block copolymer PAI-3-B1 presented the best comprehensive performance with high transparency (T500nm) of 87%, low CTE of 16 ppm/K and high tensile modulus of 6.1 GPa.

A series of new pyrene tagged nitrogen heterocyclic carbene copper (NHC-Cu) molecular complexes were synthesized and characterized by 1H- and 13C-NMR, high resolution ESI-mass spectrometry (HR-MS). The corresponding NHC-Cu complex was immobilized onto the surface of multi-walled carbon nanotubes (MWNTs) by using π-π stacking interaction, the noncovalent immobilization catalytic material MWNTs@NHC-Cu were characterized by FT-IR, XRD, XPS, thermogravimetry (TGA) and TEM. The new NHC-Cu complexes were tested both in the homogeneous phase and once immobilized onto multi-walled carbon nanotubes support for the azide-alkyne cycloaddition reaction. Both were active in the two-component click cycloaddition reaction of terminal alkynes and organic azides and three-component cycloaddition reaction that employs various terminal alkynes, NaN3 and organic halides with the advantage of excellent yields, low catalyst dosage, short reaction time. The MWNTs@NHC-Cu catalyst could be separated from the reaction system at the end of the reaction and reused in another catalytic cycle, but with loss of product yield.

Coherent modulation imaging (CMI) has been shown to be an effective lensless diffraction approach to imaging general extended samples with fast algorithmic convergence and high robustness to data imperfection. In the reported phasing algorithms of CMI, an exact knowledge of modulator is used as a priori. Extra characterization of the modulator is thus required before the CMI experiments are conducted and this can be cumbersome. Here we propose a modulator refinement algorithm that allows for modulator refinement in the same iterative process of image reconstruction. We demonstrate the method for both near-field and far-field geometries in simulations and for a far-field experiment. A relaxed requirement on exactly knowing the modulator would turn CMI into a standalone technique and make it much easier to implement, thus open up its wider applications in biology and materials science.

Neuroinflammation significantly contributes to brain injury and neurological deterioration following intracerebral hemorrhage (ICH). MicroRNA-152(miR-152) was reported to be downregulated in ICH patients and to possess anti-inflammatory properties in other diseases. In this study, we aimed to explore the role of miR-152 in ICH, and the underlying mechanisms, using a collagenase-induced rat ICH model and hemin-exposure as a cell model. We first confirmed that miR-152 was consistently downregulated in both models. Overexpression of miR-152 in microglial BV2 cells reduced hemin-induced inflammatory response and reactive oxygen species (ROS) generation, thus protecting co-cultured neuronal HT22 cells. Moreover, overexpression of miR-152 by intracerebroventricular lentivirus injection in ICH rats significantly alleviated neurodecifits, brain edema, and hematoma. These changes were associated with a marked reduction in ICH-induced neuronal death, as detected by co-staining of NeuN and TUNEL, and ICH-induced neuroinflammation, as revealed by inflammatory cytokine levels as well as by the number of Iba1 positive-stained cells in the perihematomal region. Mechanistically, miR-152 significantly inhibited ICH-induced TXNIP expression, and its overexpression blocked the interaction between TXNIP and NOD-like receptor pyrin domain containing 3(NLRP3), thus inhibiting NLRP3-driven inflammasome activation to attenuate neuroinflammation in vivo and in vitro. Moreover, the results of si-TXNIP transfection further confirmed that TXNIP inhibition was involved in the reduction of NLRP3 inflammasome activation by the overexpression of miR-152. Collectively, the present study demonstrates that miR-152 confers protection against ICH-induced neuroinflammation and brain injury by inhibiting TXNIP-mediated NLRP3 inflammasome activation, indicating a potential strategy for ICH treatment.

A novel synthetic approach to functionalized indolo[2,3-a]quinolizidines is developed via an N-heterocyclic carbene (NHC)-catalyzed annulation of cyclic β-enamino esters 1 with enals 2. This methodology offers a pathway for quick and efficient construction of an indolo[2,3-a]quinolizidine skeleton which is a core structure of many natural products with diverse bioactivities.

Neuroinflammation plays a critical role in the pathogenesis of intracerebral hemorrhage (ICH), contributing to detrimental brain injury and neurological function deficits. MicroRNA-23b (miR-23b) exerts anti-inflammatory effects in many diseases and is downregulated in patients with ICH. This study aimed to evaluate the involvement of miR-23b in ICH models in vivo and in vitro, using basal ganglia injection of collagenase type VII in rats and hemin stimulation for cells, respectively. Exogenous overexpression of miR-23b by transfection with lentivirus-miR-23b (LV-miR-23b) or miR-23b mimics was evaluated by RT-qPCR. In this study, we found miR-23b was downregulated in the ICH models and its overexpression effectively alleviated neurological deficits, brain edema, hematoma area, and neuronal apoptosis in ICH rats. Western blotting for neuroinflammation markers and immunofluorescence staining for microglial activation demonstrated that miR-23b could alleviate neuroinflammation in ICH in vivo. We also performed an in vitro mechanism study using BV2 microglial cells and HT22 neuronal cell lines to explore how miR-23b modulates neuroinflammation and neuronal protection after ICH. We found that miR-23b significantly decreased hemin-stimulated inflammation response in BV2 cells and attenuated co-cultured HT22 neuronal cell death. Additionally, we verified that miR-23b suppressed inflammation in BV2 cells by targeting inositol polyphosphate multikinase (IPMK) and that autophagy regulation through the Akt/mTOR pathway was involved in miR-23b-regulated inflammation after ICH. Our study illustrated that miR-23b played a protective role in ICH through inhibiting neuroinflammation by targeting IPMK; this mechanism may be related to the regulation of the Akt/mTOR autophagy pathway, making it a potential target for ICH treatment.