Microorganisms produce diverse polymers for various purposes such as storing genetic information, energy, and reducing power, and serving as structural materials and scaffolds. Among these polymers, ...polyhydroxyalkanoates (PHAs) are microbial polyesters synthesized and accumulated intracellularly as a storage material of carbon, energy, and reducing power under unfavorable growth conditions in the presence of excess carbon source. PHAs have attracted considerable attention for their wide range of applications in industrial and medical fields. Since the first discovery of PHA accumulating bacteria about 100 years ago, remarkable advances have been made in the understanding of PHA biosynthesis and metabolic engineering of microorganisms toward developing efficient PHA producers. Recently, nonnatural polyesters have also been synthesized by metabolically engineered microorganisms, which opened a new avenue toward sustainable production of more diverse plastics. Herein, the current state of PHAs and nonnatural polyesters is reviewed, covering mechanisms of microbial polyester biosynthesis, metabolic pathways, and enzymes involved in biosynthesis of short‐chain‐length PHAs, medium‐chain‐length PHAs, and nonnatural polyesters, especially 2‐hydroxyacid‐containing polyesters, metabolic engineering strategies to produce novel polymers and enhance production capabilities and fermentation, and downstream processing strategies for cost‐effective production of these microbial polyesters. In addition, the applications of PHAs and prospects are discussed.
Polyhydroxyalkanoates (PHAs) are biodegradable and bio‐based polymers that can substitute petroleum‐based plastics currently in use. A comprehensive overview of the mechanisms and metabolism of PHA biosynthesis, and strategies for strain development, fermentation, and downstream processing toward the cost‐effective production of natural and nonnatural polyesters having diverse material properties is provided. Additionally, applications of PHAs and future prospects are discussed.
Activated macrophages have the potential to be ideal targets for imaging inflammation. However, probe selectivity over non-activated macrophages and probe delivery to target tissue have been ...challenging. Here, we report a small molecule probe specific for activated macrophages, called CDg16, and demonstrate its application to visualizing inflammatory atherosclerotic plaques in vivo. Through a systematic transporter screen using a CRISPR activation library, we identify the orphan transporter Slc18b1/SLC18B1 as the gating target of CDg16.
Neuromorphic hardware computing is a promising alternative to von Neumann computing by virtue of its parallel computation and low power consumption. To implement neuromorphic hardware based on deep ...neural network (DNN), a number of synaptic devices should be interconnected with neuron devices. For ideal hardware DNN, not only scalability and low power consumption, but also a linear and symmetric conductance change with a large number of conductance levels is required. Here, an all‐solid‐state polymer electrolyte‐gated synaptic transistor (pEGST) is fabricated on an entire silicon wafer with CMOS microfabrication and initiated chemical vapor deposition process. The pEGST shows good linearity as well as symmetry in potentiation and depression, conductance levels up to 8,192, and low switching energy smaller than 20 fJ pulse−1. Selected 128 levels from 8,192 are used to identify handwritten digits in the MNIST database with the aid of a multilayer perceptron, resulting in a recognition rate of 91.7%.
An all‐solid‐state polymer electrolyte‐gated synaptic transistor (pEGST) is fabricated on an entire silicon wafer with CMOS microfabrication and initiated chemical vapor deposition process. The pEGST shows good linearity as well as symmetry in potentiation and depression, conductance levels up to 8,192, and low switching energy smaller than 20 fJ pulse−1.
Objective
Interferon regulatory factor 1 (IRF1) is a transcriptional regulator conventionally associated with immunomodulation. Recent molecular analyses mapping DNA binding sites of IRF1 have ...suggested its potential function in DNA repair. However, the physiologic significance of this noncanonical function remains unexplored. Here, we investigated the role of IRF1 in osteoarthritis (OA), a condition marked by senescence and chronic joint inflammation.
Methods
OA progression was examined in wild‐type and Irf1−/− mice using histologic assessments and microcomputed tomography analysis of whole‐joint OA manifestations and behavioral assessments of joint pain. An integrated analysis of assay for transposase‐accessible chromatin with sequencing and whole transcriptome data was conducted for the functional assessment of IRF1 in chondrocytes. The role of IRF1 in DNA repair and senescence was investigated by assaying γ‐H2AX foci and senescence‐associated beta‐galactosidase activity.
Results
Our genome‐wide investigation of IRF1 footprinting in chondrocytes revealed its primary occupancies in the promoters of DNA repair genes without noticeable footprint patterns in those of interferon‐responsive genes. Chondrocytes lacking IRF1 accumulated irreversible DNA damage under oxidative stress, facilitating their entry into cellular senescence. IRF1 was down‐regulated in the cartilage of human and mouse OA. Although IRF1 overexpression did not elicit an inflammatory response in joints or affect OA development, genetic deletion of Irf1 caused enhanced chondrocyte senescence and exacerbated post‐traumatic OA in mice.
Conclusion
IRF1 offers DNA damage surveillance in chondrocytes, protecting them from oxidative stress associated with OA risk factors. Our study provides a crucial and cautionary perspective that compromising IRF1 activity renders chondrocytes vulnerable to cellular senescence and promotes OA development.
Several CRISPR-Cas9 orthologues have been used for genome editing. Here, we present the smallest Cas9 orthologue characterized to date, derived from Campylobacter jejuni (CjCas9), for efficient ...genome editing in vivo. After determining protospacer-adjacent motif (PAM) sequences and optimizing single-guide RNA (sgRNA) length, we package the CjCas9 gene, its sgRNA sequence, and a marker gene in an all-in-one adeno-associated virus (AAV) vector and produce the resulting virus at a high titer. CjCas9 is highly specific, cleaving only a limited number of sites in the human or mouse genome. CjCas9, delivered via AAV, induces targeted mutations at high frequencies in mouse muscle cells or retinal pigment epithelium (RPE) cells. Furthermore, CjCas9 targeted to the Vegfa or Hif1a gene in RPE cells reduces the size of laser-induced choroidal neovascularization, suggesting that in vivo genome editing with CjCas9 is a new option for the treatment of age-related macular degeneration.
This paper is concerned with the delay-dependent stability for the linear systems with a time-varying delay. To get a result in the form of LMI from a Lyapunov–Krasovskii functional, an integral ...inequality is necessary and Jensen inequality has been a most powerful inequality in the last few years. Recently, based on Wirtinger inequality, an improved integral inequality, encompassing Jensen inequality, was proposed and its application to the stability showed a quite improvement. In this paper, without using Wirtinger inequality, a further improved integral inequality in the form of infinite series is derived, and, based on this, a delay-dependent stability condition in the form of LMI is derived. Finally, its contribution on the stability criterion is shown by well-known two examples.
Superhydrophobic and superoleophobic surfaces have so far been made by roughening a hydrophobic material. However, no surfaces were able to repel extremely-low-energy liquids such as fluorinated ...solvents, which completely wet even the most hydrophobic material. We show how roughness alone, if made of a specific doubly reentrant structure that enables very low liquid-solid contact fraction, can render the surface of any material superrepellent. Starting from a completely wettable material (silica), we micro- and nanostructure its surface to make it superomniphobic and bounce off all available liquids, including perfluorohexane. The same superomniphobicity is further confirmed with identical surfaces of a metal and a polymer. Free of any hydrophobic coating, the superomniphobic silica surface also withstands temperatures over 1000°C and resists biofouling.
The associations of Internet addiction (IA) and smartphone addiction (SA) with mental health problems have been widely studied. We investigated the effects of IA and SA on depression and anxiety ...while adjusting for sociodemographic variables. In this study, 4854 participants completed a cross-sectional web-based survey including socio-demographic items, the Korean Scale for Internet Addiction, the Smartphone Addiction Proneness Scale, and the subscales of the Symptom Checklist 90 Items-Revised. The participants were classified into IA, SA, and normal use (NU) groups. To reduce sampling bias, we applied the propensity score matching method based on genetics matching. The IA group showed an increased risk of depression (relative risk 1.207;
< 0.001) and anxiety (relative risk 1.264;
< 0.001) compared to NUs. The SA group also showed an increased risk of depression (relative risk 1.337;
< 0.001) and anxiety (relative risk 1.402;
< 0.001) compared to NCs. These findings show that both, IA and SA, exerted significant effects on depression and anxiety. Moreover, our findings showed that SA has a stronger relationship with depression and anxiety, stronger than IA, and emphasized the need for prevention and management policy of the excessive smartphone use.
The ability to manipulate droplets on a substrate using electric signals
-known as digital microfluidics-is used in optical
, biomedical
, thermal
and electronic
applications and has led to ...commercially available liquid lenses
and diagnostics kits
. Such electrical actuation is mainly achieved by electrowetting, with droplets attracted towards and spreading on a conductive substrate in response to an applied voltage. To ensure strong and practical actuation, the substrate is covered with a dielectric layer and a hydrophobic topcoat for electrowetting-on-dielectric (EWOD)
; this increases the actuation voltage (to about 100 volts) and can compromise reliability owing to dielectric breakdown
, electric charging
and biofouling
. Here we demonstrate droplet manipulation that uses electrical signals to induce the liquid to dewet, rather than wet, a hydrophilic conductive substrate without the need for added layers. In this electrodewetting mechanism, which is phenomenologically opposite to electrowetting, the liquid-substrate interaction is not controlled directly by electric field but instead by field-induced attachment and detachment of ionic surfactants to the substrate. We show that this actuation mechanism can perform all the basic fluidic operations of digital microfluidics using water on doped silicon wafers in air, with only ±2.5 volts of driving voltage, a few microamperes of current and about 0.015 times the critical micelle concentration of an ionic surfactant. The system can also handle common buffers and organic solvents, promising a simple and reliable microfluidic platform for a broad range of applications.
PDF
