Myxobacteria are famous for their capacity for social behavior and natural product biosynthesis. The unique sociality of myxobacteria is not only an intriguing scientific topic but also the main ...limiting factor for their manipulation. After more than half a century of research, a series of genetic techniques for myxobacteria have been developed, rendering these mysterious bacteria manipulable. Here, we review the advances in genetic manipulation of myxobacteria, with a particular focus on the exploitation of secondary metabolism. We emphasize the necessity and urgency of constructing the myxobacterial chassis for synthetic biology research and the exploitation of untapped secondary metabolism.
Display omitted
Enzymes that catalyse CpG methylation in DNA, including the DNA methyltransferases 1 (DNMT1), 3A (DNMT3A) and 3B (DNMT3B), are indispensable for mammalian tissue development and homeostasis
. They ...are also implicated in human developmental disorders and cancers
, supporting the critical role of DNA methylation in the specification and maintenance of cell fate. Previous studies have suggested that post-translational modifications of histones are involved in specifying patterns of DNA methyltransferase localization and DNA methylation at promoters and actively transcribed gene bodies
. However, the mechanisms that control the establishment and maintenance of intergenic DNA methylation remain poorly understood. Tatton-Brown-Rahman syndrome (TBRS) is a childhood overgrowth disorder that is defined by germline mutations in DNMT3A. TBRS shares clinical features with Sotos syndrome (which is caused by haploinsufficiency of NSD1, a histone methyltransferase that catalyses the dimethylation of histone H3 at K36 (H3K36me2)
), which suggests that there is a mechanistic link between these two diseases. Here we report that NSD1-mediated H3K36me2 is required for the recruitment of DNMT3A and maintenance of DNA methylation at intergenic regions. Genome-wide analysis shows that the binding and activity of DNMT3A colocalize with H3K36me2 at non-coding regions of euchromatin. Genetic ablation of Nsd1 and its paralogue Nsd2 in mouse cells results in a redistribution of DNMT3A to H3K36me3-modified gene bodies and a reduction in the methylation of intergenic DNA. Blood samples from patients with Sotos syndrome and NSD1-mutant tumours also exhibit hypomethylation of intergenic DNA. The PWWP domain of DNMT3A shows dual recognition of H3K36me2 and H3K36me3 in vitro, with a higher binding affinity towards H3K36me2 that is abrogated by TBRS-derived missense mutations. Together, our study reveals a trans-chromatin regulatory pathway that connects aberrant intergenic CpG methylation to human neoplastic and developmental overgrowth.
Micro-nano biorobots based on bacteria have demonstrated great potential for tumor diagnosis and treatment. The bacterial gene expression and drug release should be spatiotemporally controlled to ...avoid drug release in healthy tissues and undesired toxicity. Herein, we describe an alternating magnetic field-manipulated tumor-homing bacteria developed by genetically modifying engineered Escherichia coli with Fe
O
@lipid nanocomposites. After accumulating in orthotopic colon tumors in female mice, the paramagnetic Fe
O
nanoparticles enable the engineered bacteria to receive and convert magnetic signals into heat, thereby initiating expression of lysis proteins under the control of a heat-sensitive promoter. The engineered bacteria then lyse, releasing its anti-CD47 nanobody cargo, that is pre-expressed and within the bacteria. The robust immunogenicity of bacterial lysate cooperates with anti-CD47 nanobody to activate both innate and adaptive immune responses, generating robust antitumor effects against not only orthotopic colon tumors but also distal tumors in female mice. The magnetically engineered bacteria also enable the constant magnetic field-controlled motion for enhanced tumor targeting and increased therapeutic efficacy. Thus, the gene expression and drug release behavior of tumor-homing bacteria can be spatiotemporally manipulated in vivo by a magnetic field, achieving tumor-specific CD47 blockage and precision tumor immunotherapy.
A “two-in-one” dual activation strategy has been developed to give high-density hydrogen-bonding (HB) active units and Lewis acid (LA) active centres by immobilizing squaramides into metal–organic ...cages (MOCs). The obtained MOC served as an efficient catalyst for the chemical fixation of CO2 under mild conditions up to 99% yields with good recyclability, and the mechanism of high catalytic activity has been further explored.
The complete regression of residual tumors after photothermal therapy (PTT) depends on the activation and recognition of the immune system. However, the inevitable local inflammation after PTT in ...residual tumor recruits abundant abnormal immune cells, especially the tumor-associated macrophages (TAMs) which further promote immune escape and survival of the remaining tumor cells, resulting in the tumor recurrence and progression. To solve this problem, herein we explored biomimetic nanoparticles carrying repolarization agent of TAMs to remodel the post-PTT inflammatory microenvironment. The polydopamine nanoparticles were used simultaneously as photothermal transduction agents to ablate tumor cells and the delivery vehicles for TMP195 which can repolarize the M2-like TAMs into an antitumor phenotype. In addition, a biomimetic decoration of macrophage membrane coating was designed to endow nanoparticles the ability to actively target the tumor site after PTT mediated by inflammation-mediated chemotaxis. In the breast tumor model, these biomimetic nanoparticles with immune-modulating ability significantly elevated the levels of M1-like TAMs, ultimately resulting in a tumor-elimination rate of 60%, increased from 10% after PTT. This synergistic treatment strategy of PTT and TAMs repolarization provides a promising approach to address the deteriorated tumor microenvironment after PTT and proposes a more effective way for combinational treatment option in clinic.
•A novel three-beam impact energy harvester (TIEH) is proposed.•TIEH can be applied to low-frequency rotation and has a wide-band characteristic.•TIEH is insensitive to parameters and easy to design ...and process.•TIEH can be combined with centrifugal force to soften and harden the design.•The concept of design factor is proposed to greatly simplify the design of centrifugal force scheme.
This paper proposes a three-beam impact energy harvester (TIEH) to enhance the energy harveting efficiency for low-frequency rotational motion. The design includes three beams, including the excitation beam, the harvesting beam and the protection beam. The excitation is generated by the impact of the excitation beam and the harvesting beam, and the harvesting beam breaks through the resonance state limitation to obtain more excellent performance in the low-frequency band. Through the design of centrifugal force, the soften or harden effect can be obtained to adapt to different application scenarios. In this paper, the TIEH electromechanical coupling model is established, and the concept of design factor is proposed for the centrifugal force scheme to simplify the design and analysis. The tested TIEH can obtain 52.1 μW at 4.2 Hz with 1.9 Hz bandwidth over 2 V. The Soften TIEH has a 23.0% power increase and 15.8% bandwidth reduction and the Harden TIEH has a 11.9% power reduction and 52.6% bandwidth increase. The results show that the TIEH has the characteristics of low frequency band, wide frequency band, and parameter insensitivity, and has the potential to be applied to a low-frequency rotational structure with limited volume.
Panax notoginseng powder (PNP) has high medicinal value and is widely used in the medical and health food industries. However, the adulteration of PNP in the market has dramatically reduced its ...efficacy. Therefore, this study intends to use artificial intelligence sensory (AIS) and multi-source information fusion (MIF) technology to try to establish a quality evaluation system for different grades of PNP and adulterated Panax notoginseng powder (AD-PNP). The highest accuracy rate reached 100% in identifying PNP grade and adulteration. In the prediction of adulteration ratio and total saponin content, the optimal determination coefficients of the test set were 0.9965 and 0.9948, respectively, and the root mean square errors were 0.0109 and 0.0123, respectively. Therefore, the grade identification method of PNP and the evaluation system of AD-PNP based on AIS and MIF technology can rapidly and accurately evaluate the quality of PNP.
Food authentication and origin traceability are popular research topics, especially as concerns about food quality continue to increase. Mass spectrometry (MS) plays an indispensable role in food ...authentication and origin traceability. In this review, the applications of MS in food authentication and origin traceability by analyzing the main components and chemical fingerprints or profiles are summarized. In addition, the characteristic markers for food authentication are also reviewed, and the advantages and disadvantages of MS‐based techniques for food authentication, as well as the current trends and challenges, are discussed. The fingerprinting and profiling methods, in combination with multivariate statistical analysis, are more suitable for the authentication of high‐value foods, while characteristic marker‐based methods are more suitable for adulteration detection. Several new techniques have been introduced to the field, such as proton transfer reaction mass spectrometry, ambient ionization mass spectrometry (AIMS), and ion mobility mass spectrometry, for the determination of food adulteration due to their fast and convenient analysis. As an important trend, the miniaturization of MS offers advantages, such as small and portable instrumentation and fast and nondestructive analysis. Moreover, many applications in food authentication are using AIMS, which can help food authentication in food inspection/field analysis. This review provides a reference and guide for food authentication and traceability based on MS.
Underwater gas escape is widespread in the marine and industrial fields and the low-velocity gas caused by trace gas escape is difficult to be detected or measured. An underwater low-velocity gas ...flow measurement method based on passive acoustics with stable volume resolution is proposed in this paper. The elastic wave signal generated by the underwater gas is acquired by a hydrophone and filtered by the wavelet packet filtering method. The flow rate can be cumulatively estimated by the relationship between the bubble and the spectrum characteristics. The volume resolution of the bubble is stable, which is achieved by adjusting the signal frequency resolution. This method is adaptive to the processing of bubbles in different volumes. The stable volume resolution is helpful to reduce the random error for the cumulative continuous bubble volume estimation. Underwater gas leakage experimental platforms were established under laboratory conditions and lake conditions. The results show that the method has high accuracy and stability. For a single bubble and low-velocity flow conditions under laboratory conditions, the minimum error is 0.3% and the maximum error is 3.9% between 5 and 25 ml min−1. For the low-velocity flow under lake conditions, the minimum error is 0.8% and the maximum error is 8% between 10 and 60 ml min−1.
PDF
