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Synthetic biology aims to engineer and redesign biological systems for useful real-world applications in biomanufacturing, biosensing and biotherapy following a typical design-build-test cycle. Inspired from computer science and electronics, synthetic gene circuits have been designed to exhibit control over the flow of information in biological systems. Two types are Boolean logic inspired TRUE or FALSE digital logic and graded analog computation. Key principles for gene circuit engineering include modularity, orthogonality, predictability and reliability. Initial circuits in the field were small and hampered by a lack of modular and orthogonal components, however in recent years the library of available parts has increased vastly. New tools for high throughput DNA assembly and characterization have been developed enabling rapid prototyping, systematic in situ characterization, as well as automated design and assembly of circuits. Recently implemented computing paradigms in circuit memory and distributed computing using cell consortia will also be discussed. Finally, we will examine existing challenges in building predictable large-scale circuits including modularity, context dependency and metabolic burden as well as tools and methods used to resolve them. These new trends and techniques have the potential to accelerate design of larger gene circuits and result in an increase in our basic understanding of circuit and host behaviour.

Amaryllidaceae alkaloids (AAs) are complex plant secondary metabolites possessing a wide range of biological activities. 4′-O-methylnorbelladine (4OMN) is the branchpoint intermediate for the entire AAs, and was the last common intermediate before AA pathway branches diverge. The cyclization of 4OMN by C-C oxidative coupling, which can afford para-para ′, ortho-para ′, and para-ortho ′ scaffold, was catalyzed by cytochrome P450 96T (CYP96T) family enzymes. To clarify the mechanisms involved in this controversial step, four CYP96T homologs (LauCYP96T1, LauCYP96T1-like-1, LauCYP96T1-like-2 and LauCYP96T1-like-3) were cloned from the full-length transcriptome of Lycoris aurea . All the four LauCYP96T are localized to endoplasmic reticulum. Functional analysis reveals that LauCYP96T1 and LauCYP96T1-like proteins display inverted regioselectivity for oxidative coupling of 4OMN, in which LauCYP96T1 and LauCYP96T1-like-2 dominantly afford para-para ′ scaffold, and LauCYP96T1-like-1 and LauCYP96T1-like-3 are responsible for para-ortho ′ scaffold formation. Using molecular homology modeling and docking studies, we predicted models for the binding of 4OMN to LauCYP96T, and identified two amino acid residues that might be responsible for the dominant changes in generated products of para-ortho ′ and para-para ′ oxidative coupling. Our results highlight the functional diversity and promiscuity of LauCYP96T enzymes and might provide valuable information for Amaryllidaceae alkaloid production.

Cinnamyl alcohol dehydrogenase (CAD) plays a crucial role in lignin biosynthesis, and the gene family encoding various CAD isozymes has been cloned and characterized in numerous plant species. However, limited information regarding the CAD gene family in tobacco is currently available. In this study, we identified 10 CAD genes in Nicotiana tabacum , four in N. tomentosiformis , and six in N. sylvestris . The nucleotide and amino acid sequences of these tobacco CADs demonstrate high levels of similarity, whereas the putative protein sequences conservatively possessed two Zn 2+ binding motifs and an NADP(H) cofactor binding motif. Both NtCAD1 and NtCAD2 had conservative substrate binding sites, similar to those possessed by bona fide CADs, and evidence from phylogenetic analysis as well as expression profiling supported their role as bona fide CADs involved in lignin biosynthesis. NtCAD1 has two paralogous genes, NtCAD1–1 and NtCAD1–2 . Enzyme activity analysis revealed that NtCAD1–1 and NtCAD1–2 had a high affinity to coniferyl aldehyde, p -coumaryl aldehyde, and sinapyl aldehyde, whereas NtCAD2 preferred coniferyl aldehyde and p -coumaryl aldehyde as substrates. The kinetic parameter assay revealed that NtCAD1–2 functions as the most efficient enzyme. Downregulation of both NtCAD1–1 and NtCAD1–2 resulted in reddish-brown stems without significant changes in lignin content. Furthermore, NtCAD1–1, NtCAD1–2, and NtCAD2 showed distinct expression patterns in response to biotic and abiotic stresses, as well as different phytohormones. Our findings suggest that NtCAD1–1 and NtCAD1–2 are involved in lignin biosynthesis, with NtCAD1–2 also participating in both biological and abiotic stresses, whereas NtCAD2 plays a distinct role mainly in responding to biological and abiotic stresses in tobacco.

Efficiency of yeast transformation is determined by the rate of yeast endocytosis. The aim of this study was to investigate the effect of introducing amino acids and other nutrients (inositol, adenine, or p-aminobenzoic acid) in the transformation medium to develop a highly efficient yeast transformation protocol. The target of rapamycin complex 1 (TORC1) kinase signalling complex influences the rate of yeast endocytosis. TORC signaling is induced by amino acids in the media. Here, we found that increasing the concentration of amino acids and other nutrients in the growth media lead to an increase yeast transformation efficiency up to 10 7 CFU per μg plasmid DNA and per 10 8 cells with a 13.8 kb plasmid DNA. This is over 130 times that of current published methods. This improvement may facilitate more efficient experimentation in which transformation efficiency is critical, such as yeast two-hybrid screening.

This study aimed to investigate the effects of single nucleotide polymorphisms (SNPs) in progestogen-associated endometrial protein ( PAEP ), keratin 10 ( KRT 10), and bone morphogenetic protein 7 ( BMP 7) genes on reproductive traits (total number of piglets born, number of piglets born alive, litter birth weight, number of piglets weaned and litter weight weaned) in Kele pigs. We used 255 multiparous Kele sow (2–4 parities) as research materials. SNPs were identified by using a PCR amplification instrument and sequence alignment software DANMAN. The population genetic characteristics of SNPs were analyzed using the SHEsis online software. Bioinformatics analyses of SNPs were conducted using RNAfold, SOPMA, SWISS-MODEL, and Swiss-PdbViewer programs. The associations between the SNPs and reproductive traits in Kele pigs were analyzed through SPSS 22.0 software. In this study, nine SNPs were identified in the three genes: g.1884992 T > C (exon 4), g.1885125 G > C (intron 4), and g.1885158 G > A (intron 4) in PAEP , g.21643703 C > T (intron 4), g.21643714 G > A (intron 4) and g.21643741 G > A (exon 5) in KRT 10, and g.57647887 G > A (intron 3), g.57647990 C > T (intron 3) and g.57648145 C > G (intron 3) in BMP 7. In SNPs g.1884992 T > C of PAEP, missense mutation eventuated structural changes in mRNA and proteins’ secondary structure. In SNPs g.21643741 G > A of KRT 10 , the synonymous mutation led to an alteration in mRNA secondary structure. For PAEP, the CC genotype in SNPs g.1885125 G > C and the AA genotype in SNPs g.1885158 G > A showed significantly higher values than other genotypes in all reproduction traits except for litter birth weight, preliminarily identified as the favorable genotypes. For KRT 10, the GG genotype in SNPs g.21648641 G > A showed significant superiority to the AA genotype ( P < 0.05) in all aspects except for litter birth weight and notably surpassed the GA genotype in the total number of piglets born ( P < 0.05), preliminarily recognized as a favorable genotype. Regarding BMP 7, the GA genotype in SNPs g.57647887 G > A and the CT genotype in SNPs g.57647990 C > T exhibited significantly higher number of piglets born alive and number of piglets born alive compared to other genotypes ( P < 0.05). The GG genotype in SNPs g.57648145 C > G was significantly associated with higher litter birth weight ( P < 0.05). The result of diplotype analyses indicated that the H3H3 (CCGGGG) of PAEP and H3H3 (CCGGAA) of KRT 10 had a significant effect on the five traits. For BMP 7, the H4H4 (AATTGG) diplotype showed a significant influence on all genotypes except litter birth weight.

Chinese medicine is a complex system guided by traditional Chinese medicine (TCM) theories, which has proven to be especially effective in treating chronic and complex diseases. However, the underlying modes of action (MOA) are not always systematically investigated. Herein, a systematic study was designed to elucidate the multi-compound, multi-target and multi-pathway MOA of a Chinese medicine, QiShenYiQi (QSYQ), on myocardial infarction. QSYQ is composed of Astragalus membranaceus (Huangqi), Salvia miltiorrhiza (Danshen), Panax notoginseng (Sanqi), and Dalbergia odorifera (Jiangxiang). Male Sprague Dawley rat model of myocardial infarction were administered QSYQ intragastrically for 7 days while the control group was not treated. The differentially expressed genes (DEGs) were identified from myocardial infarction rat model treated with QSYQ, followed by constructing a cardiovascular disease (CVD)-related multilevel compound-target-pathway network connecting main compounds to those DEGs supported by literature evidences and the pathways that are functionally enriched in ArrayTrack. 55 potential targets of QSYQ were identified, of which 14 were confirmed in CVD-related literatures with experimental supporting evidences. Furthermore, three sesquiterpene components of QSYQ, Trans-nerolidol, (3S,6S,7R)-3,7,11-trimethyl-3,6-epoxy-1,10-dodecadien-7-ol and (3S,6R,7R)-3,7,11-trimethyl-3,6-epoxy-1,10-dodecadien-7-ol from Dalbergia odorifera T. Chen, were validated experimentally in this study. Their anti-inflammatory effects and potential targets including extracellular signal-regulated kinase-1/2, peroxisome proliferator-activated receptor-gamma and heme oxygenase-1 were identified. Finally, through a three-level compound-target-pathway network with experimental analysis, our study depicts a complex MOA of QSYQ on myocardial infarction.

In this study, BiSe nanosheets were obtained by exfoliating bulk BiSe in liquid phase, and the prepared BiSe nanosheets were used as photoanode to construct photoelectrochemical (PEC) photodetectors with high photoresponse performance. At a light intensity of 80 mW/cm 2 and a bias potential of 0.4 V, the photocurrent density reaches 0.089 μA/cm 2 , which is about 2.5 times that of the bulk BiSe. Further, the photocurrent density increased from 0.089 μA/cm 2 to 0.18 μA/cm 2 after the addition of photosynthesis-inspired additives (ATP and NADPH) to the electrolyte, and the rise time decreased significantly from 1.76 s to 0.13 s. The decay time was also significantly reduced from 2.27 s to 0.18 s. The improvement of photoresponse performance is due to the synergistic effect of ATP and NADPH, which inhibits the photogenerated electron–hole pair recombination and promotes the PEC reaction. The successful preparation of this high-performance photodetector is mainly due to the fact that the liquid-phase exfoliation effectively increases the specific surface of BiSe, and the introduced ATP and NADPH further improve the circulation and utilization of the photogenic carrier to promote the PEC reaction. This study provides a reference for the further research of BiSe materials in the field of photodetection, and confirms the feasibility of improving the performance of photodetectors through the combination of liquid-phase exfoliation to change the morphology characteristics and photosynthesizing electrolyte additives.

Methyltransferase-like 23 (METTL23) is a kind of RNA methyltransferase that catalyzes the methylation transfer to the N6-adenosine of RNA, serving as one of the key mediators in this process. However, the METTL23 gene has been poorly researched in pigs. In this study, we investigated the genetic effects of METTL23 single-nucleotide polymorphism(SNPs) on reproductive traits in Kele pigs. The DNA was extracted from 228 healthy multiparous Kele sows, and Sanger sequencing revealed three SNPs, g.4804958 G > T (intron 2), g.4805082 C > T (exon 2), and g.4806821 A > G (exon 3). The polymorphism information content (PIC) for each SNP was 0.264, 0.25, and 0.354, indicating moderate polymorphism (0.25 < PIC < 0.5) and providing genetic information. Linkage disequilibrium analysis showed no strong linkage disequilibrium between the three SNPs. The association analysis revealed that in the SNP g.4804958 G > T individuals with the GG genotype had a significantly higher number of piglets born alive, litter birth weight, number of weaned piglets, and weaning litter weight compared to those with the TT genotype (p < 0.05). Individuals with the GG genotype in the SNP g.4806821 A > G group had significantly higher litter birth weight and average birth weight than those with the AA genotype (p < 0.05). The H4H4 diplotype showed significant effects on the number of piglets born alive, litter birth weight, number of weaned piglets, weaning litter weight, and weaning weight (p < 0.05). Together, the METTL23 gene could be used as a candidate gene for the selection of reproductive traits in Kele pigs.

Oral ulcers can be addressed using various biomaterials designed to deliver medications or cytokines. Nevertheless, the effectiveness of these substances is frequently limited in many patients due to poor adherence, short retention time in the mouth, and less‐than‐optimal drug efficacy. In this study, a new hydrogel patch (FSH3) made of a silk fibroin/hyaluronic acid matrix with light‐sensitive adhesive qualities infused with ferric iron/shikonin nanoparticles to enhance healing effects is presented. Initially, this hydrogel forms an adhesive barrier over mucosal lesions through a straightforward local injection, solidifying when exposed to UV light. Subsequently, FSH3 demonstrates superior reactive oxygen species elimination and near‐infrared photothermal bactericidal activity. These characteristics support bacterial elimination and regulate oxidative levels, promoting a wound's progression from inflammation to tissue regeneration. In a diabetic rat model mimicking oral ulcers, FSH3 significantly speeds up healing by adjusting the inflammatory environment of the injured tissue, maintaining balance in oral microbiota, and promoting faster re‐epithelialization. Overall, the light‐sensitive FSH3 hydrogel shows potential for rapid wound recovery and may transform therapeutic methods for managing oral ulcers in diabetes. A novel light‐responsive hydrogel (FSH3) is crafted for treating diabetic oral ulcers. Upon application at the affected area, FSH3 binds robustly, delivering outstanding performance in eliminating reactive oxygen species and providing near‐infrared photothermal bactericidal effects. It successfully eradicates bacteria and adjusts the oxidative environment to enhance wound healing.

Photothermal therapy possesses great advantages for the treatment of drug-resistant tumors. Herein, Near Infrared (NIR)-triggered photothermal nanoparticles were developed through loading indocyanine green (ICG), a kind of NIR dye, into amino group-modified silica nanoparticles (SiO2-NH2 NPs). SiO2-NH2 NPs were prepared with immobilization of the amino groups into the framework of silica nanoparticles (SiO2 NPs) by employing (3-aminopropyl)-triethoxysilane (APTES). Before and after the modification of the amino group, the particle sizes of SiO2 NPs showed similar value, around 100 nm. ICG was further adsorbed into SiO2-NH2 NPs by electrostatic attraction to enable SiO2-NH2@ICG NPs as a kind of photothermal agent. The loading rate of ICG to SiO2-NH2 was greatly increased compared to unmodified SiO2, and the stability of ICG was also improved. Moreover, the SiO2-NH2@ICG NPs exhibited efficient photothermal effects due to ICG transforming laser power into local heat through the connected ICG, when NIR laser irradiation turned on for a couple of minutes. Finally, the in vitro antitumor efficacy of SiO2-NH2@ICG NPs was investigated by recording cell proliferation rate and further chronicled the apoptotic morphology evidence by a Calcein-AM/PI fluorescent staining assay, indicating the efficient photothermal targeted therapy for the HepG2 tumor cells.