A bionic self-driven retinomorphic eye with ionogel photosynaptic retina.

Bioinspired bionic eyes should be self-driving, repairable and conformal to arbitrary geometries. Such eye would enable wide-field detection and efficient visual signal processing without requiring external energy, along with retinal transplantation by replacing dysfunctional photoreceptors with healthy ones for vision restoration. A variety of artificial eyes have been constructed with hemispherical silicon, perovskite and heterostructure photoreceptors, but creating zero-powered retinomorphic system with transplantable conformal features remains elusive. By combining neuromorphic principle with retinal and ionoelastomer engineering, we demonstrate a self-driven hemispherical retinomorphic eye with elastomeric retina made of ionogel heterojunction as photoreceptors. The receptor driven by photothermoelectric effect shows photoperception with broadband light detection (365 to 970 nm), wide field-of-view (180°) and photosynaptic (paired-pulse facilitation index, 153%) behaviors for biosimilar visual learning. The retinal photoreceptors are transplantable and conformal to any complex surface, enabling visual restoration for dynamic optical imaging and motion tracking.

Phase-Segregated Ductile Eutectogels with Ultrahigh Modulus and Toughness for Antidamaging Fabric Perception.

Ionogels are extremely soft ionic materials that can undergo large deformation while maintaining their structural and functional integrity. Ductile ionogels can absorb energy and resist fracture under external load, making them an ideal candidate for wearable electronics, soft robotics, and protective gear. However, developing high-modulus ionogels with extreme toughness remains challenging. Here, a facile one-step photopolymerization approach to construct an acrylic acid (AA)-2-hydroxyethylacrylate (HEA)-choline chloride (ChCl) eutectogel (AHCE) with ultrahigh modulus and toughness is reported. With rich hydrogen bonding crosslinks and phase segregation, this gel has a 99.1 MPa Young's modulus and a 70.6 MJ m-3 toughness along with 511.4% elongation, which can lift 12 000 times its weight. These features provide extreme damage resistance and electrical healing ability, offering it a protective and strain-sensitive coating to innovate anticutting fabric with motion detection for human healthcare. The work provides an effective strategy to construct robust ionogel materials and smart wearable electronics for intelligent life.

Fermented mixed feed alters growth performance, carcass traits, meat quality and muscle fatty acid and amino acid profiles in finishing pigs.

This study was conducted to investigate the effects of fermented mixed feed (FMF) on growth performance, carcass traits, meat quality, muscle amino acid and fatty acid composition and mRNA expression levels of genes related to lipid metabolism in finishing pigs. In the present study, 144 finishing pigs (Duroc × Berkshire × Jiaxing Black) were randomly allocated to 3 dietary treatments with 4 replicate pens per group and 12 pigs per pen. The dietary treatments included a basal diet (CON), a basal diet + 5% FMF and a basal diet + 10% FMF. The experiment lasted 38 d after 4 d of acclimation. The results showed that 5% and 10% FMF significantly increased the average daily gain (ADG) of the females but not the males (P < 0.05), but FMF supplementation showed no impact on carcass traits. Moreover, 10% FMF supplementation increased the meat color45 min and meat color24 h values, while it decreased the shear force relative to CON (P < 0.05). In addition, 10% FMF significantly increased the contents of flavor amino acids (FAA), total essential AA (EAA), total non-EAA (NEAA) and total AA relative to CON (P < 0.05). Furthermore, the diet supplemented with 10% FMF significantly increased the concentration of n-3 polyunsaturated fatty acids (PUFA), n-6 PUFA and total PUFA, and the PUFA to saturated fatty acids ratio (P < 0.05), suggesting that FMF supplementation increased meat quality. Moreover, compared with the CON, 10% FMF supplementation increased the mRNA expression of lipogenic genes, including CEBPα, PPARγ, SREBP1 and FABP4, and upregulated the expression of unsaturated fatty acid synthesis (ACAA1 and FADS2). Together, our results suggest that 10% FMF dietary supplementation improved the female pigs' growth performance, improved the meat quality and altered the profiles of muscle fatty acids and amino acids in finishing pigs. This study provides a reference for the production of high-quality pork.

A visualization reporter system for characterizing antibiotic biosynthetic gene clusters expression with high-sensitivity.

The crisis of antibiotic resistance has become an impending global problem. Genome sequencing reveals that streptomycetes have the potential to produce many more bioactive compounds that may combat the emerging pathogens. The existing challenge is to devise sensitive reporter systems for mining valuable antibiotics. Here, we report a visualization reporter system based on Gram-negative bacterial acyl-homoserine lactone quorum-sensing (VRS-bAHL). AHL synthase gene (cviI) of Chromobacterium violaceum as reporter gene is expressed in Gram-positive Streptomyces to synthesize AHL, which is detected with CV026, an AHL deficient mutant of C. violaceum, via its violacein production upon AHL induction. Validation assays prove that VRS-bAHL can be widely used for characterizing gene expression in Streptomyces. With the guidance of VRS-bAHL, a novel oxazolomycin derivative is discovered to the best of our knowledge. The results demonstrate that VRS-bAHL is a powerful tool for advancing genetic regulation studies and discovering valuable active metabolites in microorganisms.

A butenolide signaling system synergized with biosynthetic gene modules led to effective activation and enhancement of silent oviedomycin production in Streptomyces.

Secondary metabolic gene clusters widely exist in the genomes of Streptomyces but mostly remain silent. To awaken this hidden reservoir of natural products, various strategies concerning secondary metabolic pathways are applied. Here, we describe that butenolide signaling molecule deficiency and glucose addition can interdependently activate the expression of silent oviedomycin biosynthetic gene clusters in Streptomyces ansochromogenes and Streptomyces antibioticus. Since oviedomycin is a promising anti-tumor lead compound, in order to improve its yield, we use the cluster-situated genes (ovmF, ovmG, ovmI and ovmH) encoding the enzymes for acyl carrier protein modification and precursor biosynthesis, and the discrete precursor biosynthetic genes (pyk2, gap1 and accA2) involved in glycolysis to assemble two gene modules (pFGIH and pPGA). Their co-overexpression in ΔsabA (a disruption mutant of sabA encoding SAB synthase) has superimposed effect on the yield of oviedomycin, which can be further increased to 59-fold in the presence of galactose as optimal carbon source. This is the most unambiguous evidence that butenolide signaling system can synergize with the optimization of primary metabolism to regulate the expression of secondary metabolic gene clusters, providing efficient strategies for mining natural products of Streptomyces.

A widespread response of Gram-negative bacterial acyl-homoserine lactone receptors to Gram-positive Streptomyces γ-butyrolactone signaling molecules.

Cell-cell communication is critical for bacterial survival in natural habitats, in which miscellaneous regulatory networks are encompassed. However, elucidating the interaction networks of a microbial community has been hindered by the population complexity. This study reveals that γ-butyrolactone (GBL) molecules from Streptomyces species, the major antibiotic producers, can directly bind to the acyl-homoserine lactone (AHL) receptor of Chromobacterium violaceum and influence violacein production controlled by the quorum sensing (QS) system. Subsequently, the widespread responses of more Gram-negative bacterial AHL receptors to Gram-positive Streptomyces signaling molecules are unveiled. Based on the cross-talk between GBL and AHL signaling systems, combinatorial regulatory circuits (CRC) are designed and proved to be workable in Escherichia coli (E. coli). It is significant that the QS systems of Gram-positive and Gram-negative bacteria can be bridged via native Streptomyces signaling molecules. These findings pave a new path for unlocking the comprehensive cell-cell communications in microbial communities and facilitate the exploitation of innovative regulatory elements for synthetic biology.

Component Optimization of Neomycin Biosynthesis via the Reconstitution of a Combinatorial Mini-Gene-Cluster in Streptomyces fradiae.

Neomycin, a multicomponent aminoglycoside antibiotic, is mainly utilized in livestock husbandry and feed additives in animals. The antimicrobial potency of the main product neomycin B is higher than that of its stereoisomer neomycin C. However, the content of neomycin C as an impurity in the high-producing strain is relatively high, and its isolation or removal from neomycin B is quite difficult, which influences the widespread application of neomycin. In this work, the essential genes responsible for neomycin biosynthesis were evaluated and overexpressed to reduce the content of neomycin C. Among them, neoG and neoH are two novel regulatory genes for neomycin biosynthesis, aphA is a resistance gene, neoN encoding a radical SAM-dependent epimerase is responsible for the conversion of neomycin C to B using SAM as the cofactor, and metK is a SAM synthetase coding gene. We demonstrated that the reconstitution and overexpression of a mini-gene-cluster (PkasO*-neoN-metK-PkasO*-neoGH-aphA) could effectively reduce the accumulation of neomycin C from 19.1 to 12.7% and simultaneously increase neomycin B by ∼13.1% in the engineered strain Sf/pKCZ04 compared with the wild-type strain (Sf). Real-time quantitative polymerase chain reaction analysis revealed the remarkable up-regulation of the neoE, neoH, neoN, and metK genes situated in the mini-gene-cluster. The findings will pave a new path for component optimization and the large-scale industrial production of significant commercial antibiotics.

Is repeated retreatment necessary for HIV-negative serofast early syphilis patients?

A persistent non-treponemal serological response can be observed in patients with syphilis after treatment and is referred to as serofast. This status makes it difficult for clinicians to judge the curative effect of treatment, particularly in patients with early syphilis. In the present study, a total of 114 eligible serofast patients treated between January 2009 and June 2016 were retrospectively analyzed. All patients were subjected to rapid plasma reagin (RPR) serological tests and followed up for 24 months. The patients who remained serofast after initial therapy were given the first retreatment, and at 12 months, those who were still serofast received a second retreatment. After the first retreatment (6 months), 33.3% of the subjects (38/114) were serologically cured (≥4-fold decline in RPR titer). At 24 months, the patients that had achieved serological cure accounted for 23.7% (18/76) of the patients that received the second retreatment. Furthermore, 26.3% of subjects that achieved serological cure (10/38) and had not been further treated after the first retreatment spontaneously presented with a ≥4-fold decline in RPR titer or negative status. In conclusion, the present study indicated that in patients with early syphilis and serofast status after initial treatment, retreatments may not provide any significant benefit. The second retreatment did not significantly improve the patient's serological cure rate. There is no evidence that patients with early syphilis and serofast should receive multiple retreatments, in spite of this being commonly performed in clinical practice.