Leucine-rich-repeat receptor-like kinases (LRR-RLKs) play central roles in sensing various signals to regulate plant development and environmental responses. The extracellular domains (ECDs) of plant ...LRR-RLKs contain LRR motifs, consisting of highly conserved residues and variable residues, and are responsible for ligand perception as a receptor or co-receptor. However, there are few comprehensive studies on the ECDs of LRR-RLKs due to the difficulty in effectively identifying the divergent LRR repeats.
In the current study, an efficient LRR motif prediction program, the "Phyto-LRR prediction" program, was developed based on the position-specific scoring matrix algorithm (PSSM) with some optimizations. This program was trained by 16-residue plant-specific LRR-highly conserved segments (HCS) from LRR-RLKs of 17 represented land plant species and a database containing more than 55,000 predicted LRRs based on this program was constructed. Both the prediction tool and database are freely available at http://phytolrr.com/ for website usage and at http://github.com/phytolrr for local usage. The LRR-RLKs were classified into 18 subgroups (SGs) according to the maximum-likelihood phylogenetic analysis of kinase domains (KDs) of the sequences. Based on the database and the SGs, the characteristics of the LRR motifs in the ECDs of the LRR-RLKs were examined, such as the arrangement of the LRRs, the solvent accessibility, the variable residues, and the N-glycosylation sites, revealing a comprehensive profile of the plant LRR-RLK ectodomains.
The "Phyto-LRR prediction" program is effective in predicting the LRR segments in plant LRR-RLKs, which, together with the database, will facilitate the exploration of plant LRR-RLKs functions. Based on the database, comprehensive sequential characteristics of the plant LRR-RLK ectodomains were profiled and analyzed.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A DNA-based stimulus-responsive drug delivery system for synergetic cancer therapy has been developed. The system is built on a triplex-DNA nanoswitch capable of precisely responding to pH variations ...in the range of ∼5.0–7.0. In extracellular neutral pH space, the DNA nanoswitch keeps a linear conformation, immobilizing multiple therapeutics such as small molecules and antisense compounds simultaneously. Following targeted cancer cell uptake via endocytosis, the nanoswitch inside acidic intracellular compartments goes through a conformational change from linear to triplex, leading to smart release of the therapeutic combination. This stimuli-responsive drug delivery system does not rely on artificial responsive materials, making it biocompatible. Furthermore, it enables simultaneous delivery of multiple therapeutics for enhanced efficacy. Using tumor-bearing mouse models, we show efficient gene silencing and significant inhibition of tumor growth upon intravenous administration of the smart nanoswitch, providing opportunities for combinatorial cancer therapy.
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IJS, KILJ, NUK, PNG, UL, UM
The delivery of mRNA to manipulate protein expression has attracted widespread attention, since that mRNA overcomes the problem of infection and mutation risks in transgenes and can work as drugs for ...the treatment of diseases. Although there are currently some vehicles that deliver mRNA into cells, they have not yet reached a good balance in terms of expression efficiency and biocompatibility. Here, a DNA nano‐hydrogel system for mRNA delivery is developed. The nano‐hydrogel is all composed of DNA except the target mRNA, so it has superior biocompatibility compared with those chemical vehicles. In parallel, the nano‐hydrogel can be compacted into a nanosphere under the crosslinking by well‐designed “X”‐shaped DNA scaffolds and DNA linkers, facilitating the delivery into cells through endocytosis. In addition, smart intracellular release of the mRNA is achieved by incorporating a pH‐responsive i‐motif structure into the nano‐hydrogel. Thus, taking the efficient delivery and release together, mRNA can be translated into the corresponding protein with a high efficiency, which is comparable to that of the commercial liposome but with a much better biocompatibility. Due to the excellent biocompatibility and efficiency, this nano‐hydrogel system is expected to become a competitive alternative for delivering functional mRNA in vivo.
Delivery of mRNA is attractive for the treatment of diseases, including the COVID‐19. But the delivery vehicles still need to be improved in terms of expression efficiency and biocompatibility. Here, a DNA nano‐hydrogel system for mRNA delivery is developed. It avoids the use of chemical reagents and can achieve pH‐responsive release of mRNA, thus balancing the expression efficiency and biocompatibility.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Due to the sudden outbreak of COVID-19 at the end of 2019, rapid detection has become an urgent need for community clinics and hospitals. The rapid development of isothermal amplification detection ...technology for nucleic acids in the field of molecular diagnostic point-of-care testing (POCT) has gained a great deal of attention in recent years. Thanks to intensive research on nicking enzymes, nicking enzyme-combined isothermal amplification has become a promising platform for rapid detection. This is a novel technique that uses nicking enzymes to improve ordinary isothermal amplification. It has garnered significant interest as it overcomes the complexity of traditional molecular diagnostics and is not subject to temperature limitations, relying on cleavage enzymes to efficiently amplify targets in a very short time to provide a high level of amplification efficiency. In recent years, several types of nicking enzyme-combined isothermal amplification have been developed and they have shown great potential in molecular diagnosis, immunodiagnosis, biochemical identification, and other fields. However, this kind of amplification has some disadvantages. In this review, the principles, advantages and disadvantages, and applications of several nicking enzyme-combined isothermal amplification techniques are reviewed and the prospects for the development of these techniques are also considered.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Nitrous acid (HONO) is a key reservoir of the hydroxyl radical (OH) and plays a central role in the atmospheric chemistry. To understand the sources and impact of HONO in the polluted atmosphere of ...northern China, continuous measurements of HONO and related parameters were conducted from September 2015 to August 2016 at an urban site in Ji'nan, the capital city of Shandong province. HONO showed well-defined seasonal and diurnal variation patterns with clear wintertime and nighttime concentration peaks. Elevated HONO concentrations (e.g., over 5 ppbv) were frequently observed with a maximum value of 8.36 ppbv. The HONO/NOX ratios of direct vehicle emissions varied in the range of 0.29%–0.87%, with a mean value of 0.53%. An average NO2-to-HONO nighttime conversion frequency (khet) was derived to be 0.0068 ± 0.0045 h−1 from 107 HONO formation cases. A detailed HONO budget analysis suggests an unexplained daytime missing source of 2.95 ppb h−1 in summer, which is about seven times larger than the homogeneous reaction of NO with OH. The effect of HONO on OH production was also quantified. HONO photolysis was the uppermost source of local OH radical throughout the daytime. This study provides the year-round continuous record of ambient HONO in the North China Plain, and offers some insights into the characteristics, sources and impacts of HONO in the polluted atmospheres of China.
•One-year continuous measurements of HONO were made at a typical urban site in northern China.•The variation characteristics and various sources strength of HONO were examined based on a large data set.•A strong missing daytime source was needed to explain the measured HONO concentrations.•HONO photolysis is the dominant OH source throughout the daytime.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Laborious and costly detection of miRNAs has brought challenges to its practical applications, especially for home health care, rigorous military medicine, and the third world. In this work, we ...present a pH-responsive miRNA amplification method, which allows the detection of miRNA just using a pH test paper. The operation is easy and no other costly instrument is involved, making the method very friendly. In our strategy, a highly efficient isothermal amplification of miRNA is achieved using an improved netlike rolling circle amplification (NRCA) technique. Large amounts of H+ can be produced as a byproduct during the amplification to induce significant changes of pH, which can be monitored directly using a pH test paper or pH-sensitive indicators. The degree of color changes depends on the amount of miRNA, making it possible for quantitative analysis. As an example, the method is successfully applied to quantify a miRNA (miR-21) in cancer cells. The results agree well with that from the prevalent qRT-PCR analysis. It is the first time that a paper-based point-of-care testing (POCT) is developed for the detection of miRNAs, which might promote the popularization of miRNAs working as biomarkers for diagnostic purposes.
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IJS, KILJ, NUK, PNG, UL, UM
Cancer is one of the leading causes of mortality worldwide, because of the lack of accurate diagnostic tools for the early stages of cancer. Thus, early diagnosis, which provides important ...information for a timely therapy of cancer, is of great significance for controlling the development of the disease and the proliferation of cancer cells and for improving the survival rates of patients. To achieve the goals of early diagnosis and timely therapy of cancer, DNA nanotechnology may be effective, since it has emerged as a valid technique for the fabrication of various nanoscale structures and devices. The resultant DNA-based nanoscale structures and devices show extraordinary performance in cancer diagnosis, owing to their predictable secondary structures, small sizes, and high biocompatibility and programmability. In particular, the rapid development of DNA nanotechnologies, such as molecular assembly technologies, endows DNA-based nanomaterials with more functionalization and intellectualization. Here, we summarize recent progress made in the development of DNA nanotechnology for the fabrication of functional and intelligent nanomaterials and highlight the prospects of this technology in cancer diagnosis and therapy.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The capability to encapsulate designated live cells into a biologically and mechanically tunable polymer layer is in high demand. Here, an approach to weave functional DNA polymer cocoons has been ...proposed as an encapsulation method. By developing in situ DNA-oriented polymerization (isDOP), we demonstrate a localized, programmable, and biocompatible encapsulation approach to graft DNA polymers onto live cells. Further guided by two mutually aided enzymatic reactions, the grafted DNA polymers are assembled into DNA polymer cocoons at the cell surface. Therefore, the coating of bacteria, yeast, and mammalian cells has been achieved. The capabilities of this approach may offer significant opportunities to engineer cell surfaces and enable the precise manipulation of the encapsulated cells, such as encoding, handling, and sorting, for many biomedical applications.
A cold-formed, thin-walled steel/fast-growing timber composite system has recently been presented for low-rise buildings. It aims to increase the use of fast-growing wood as a green building material ...in structures, thus contributing to the transformation of traditional buildings. This study proposed a composite I-beam combined with fast-growing radiata pine and cold-formed thin-walled U-shaped steel. A four-point bending test was used to measure the bending properties of steel–timber composite I-beams under various connection methods. Based on experimental results, this study examined the specimen’s failure mechanism, mechanical properties, and strain development. In addition, a method for calculating flexural bearing capacity based on the superposition principle and transformed section method was suggested. It is evident from the results that fast-growing timber and cold-formed thin-walled steel can have significant composite effects. Different connecting methods significantly impact beams’ failure mode, stiffness, and bearing capacity. Furthermore, the theoretical method for calculating the flexural bearing capacity of composite beams differs from the test value by less than 10%. This paper’s research encourages the applications of fast-growing wood as light residential components, and it serves as a reference for the development, production, and engineering of steel–timber composite structural systems.
Volatile organic compounds (VOCs) management has been recently given a high priority in China to mitigate ozone (O3) air pollution. However, there is a relatively poor understanding of VOCs due to ...their complexity and fewer observations. To better understand the pollution characteristics of VOCs and their impact on O3 pollution, two-year continuous measurements were conducted at four representative sites in Ji'nan, eastern China. These four sites cover urban, background, and industrial areas (within a petroleum refinery). Ambient VOCs showed higher concentrations at industrial site than at urban and background sites, owing to intensive emissions from petrochemical industry. The VOCs compositions present spatial heterogeneity with alkenes dominated in total reactivity at urban and background sites, while alkenes and aromatics together dominated at industrial site. The VOCs emission profile from petrochemical industry was calculated based on observational data, which revealed a huge impact on light alkanes (C2–C5), light alkenes (ethene), and aromatics (toluene and m/p-xylene). The positive matrix factorization (PMF) model analysis further refined the impact of different petrochemical industrial processes. Alkanes and alkenes dominated the emissions during refining process, while aromatics dominated during solvent usage process. Analysis by an observation-based model indicated stronger in-situ O3 production and higher sensitivity to nitrogen oxides at industrial site compared to urban and background sites. The reduction of VOCs emissions from petrochemical industry would significantly reduce the O3 concentrations. The analyses underline the significant impact of petrochemical industry on VOCs and O3 pollution, and provide important reference for the formulation of refined and effective control strategies.
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•Two-year online measurements of VOCs were conducted at four sites in a Chinese city.•Petrochemical industry led to higher VOC level and larger aromatic contribution.•Strong O3 production and high sensitivity to NOx were determined at industrial site.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP