Transcription activator-like effector nucleases （TALENs） and clustered regularly interspaced short palindromic repeats （CRISPR）/ CRISPR-associated （Cas） systems have emerged as powerful tools for ...genome editing in a variety of species. Here, we report, for the first time, targeted mutagenesis in Zea mays using TALENs and the CRISPR/Cas system. We designed five TALENs targeting 4 genes, namely ZmPDS, ZmlPKIA, ZmlPK, ZmMRP4, and obtained targeting efficiencies of up to 23.1% in protoplasts, and about 13.3% to 39.1% of the transgenic plants were somatic mutations. Also, we constructed two gRNAs targeting the ZmlPK gene in maize protoplasts, at frequencies of 16.4% and 19.1%, respectively. In addition, the CRISPR/Cas system induced targeted mutations in Z. mays protoplasts with efficiencies （13.1%） similar to those obtained with TALENs （9.1%）. Our results show that both TALENs and the CRISPR/Cas system can be used for genome modification in maize.
Blindness affects 60 million people worldwide. The leading causes of irreversible blindness include age-related macular degeneration, retinal vascular diseases and glaucoma. The unique features of ...the eye provide both benefits and challenges for drug discovery and delivery. During the past decade, the landscape for ocular drug therapy has substantially changed and our knowledge of the pathogenesis of ophthalmic diseases has grown considerably. Anti-angiogenic drugs have emerged as the most effective form of therapy for age-related macular degeneration and retinal vascular diseases. Lowering intraocular pressure is still the mainstay for glaucoma treatment but neuroprotective drugs represent a promising next-generation therapy. This Review discusses the current state of ocular drug therapy and highlights future therapeutic opportunities.
In this paper, the prescribed-time control problem for a class of uncertain nonlinear systems is investigated. By fully exploiting key properties of a class of parametric Lyapunov equations and ...constructing a time-varying Lyapunov-like function, a neat linear time-varying high gain observer-based output feedback controller is designed. The uncertain parameters of the systems are reflected in the selection of the initial gain of the time-varying high gain function in the controller. It is proved that the proposed controller can drive the state to zero at the prescribed time and the control is bounded. Numerical examples verify the effectiveness of the proposed method.
•Heat transfer enhancement based on multi-longitudinal vortices is reviewed.•Heat transfer optimization gives the optimal flow fields for heat transfer.•Generating multi-longitudinal vortices results ...in heat transfer enhancement.•Research gaps and future research directions are provided.
In this work, a review on single-phase convective heat transfer enhancement based on multi-longitudinal vortices is carried out. Theoretical investigations on convective heat transfer optimization from different principles such as entropy generation minimization principle, field synergy principle, entransy dissipation extremum principle, power consumption minimization principle, and exergy destruction minimization principle for the better trade-off between heat transfer augmentation and flow resistance reduction are firstly evaluated. It is found that the optimal flow fields are mainly characterized by multi-longitudinal vortices, implying that heat transfer enhancement techniques which can generate the flow patterns similar to the optimal flow fields may also enjoy the satisfactory balance between heat transfer enhancement and flow resistance reduction. Then, various techniques such as artificial roughness, special-shaped tubes, multiple swirl devices, and longitudinal vortex generators that can construct the flow pattern of multi-longitudinal vortices are summarized. Results indicate that most of the techniques show excellent thermal-hydraulic performance, but some techniques still suffer from high flow resistance. Based on the discussion, some new perspectives on the existing research gaps, challenging, and future research directions have been provided for the development of enhanced heat transfer techniques by generating multi-longitudinal vortices in heat exchanger tubes.
Two novel nitrogen‐doped, hexa‐peri‐hexabenzocoronene (HBC)‐based nanographenes (NGs) 1 and 2 bearing an azepine and an azocine at the fjord region, respectively, were synthesized and characterized. ...Notably, structure 1 was synthesized by Diels–Alder reaction of cyclic alkene and tetrachlorothiophene‐S,S‐dioxide, followed by Suzuki–Miyaura cross‐coupling and Scholl‐type reactions, which represents a modified strategy to construct NGs. The azo‐heptagon‐embedded NG 1 leads to a saddle shape, and the azo‐octagon‐embedded NG 2 exhibits a distorted saddle‐helix conformation with the largest torsion angle recorded so far in 5helicenes. As a result, the different structural topographies for NGs 1 and 2 lead to significant changes in the optical properties including UV absorption and fluorescent emission. Additionally, the 8π‐heterocycles azepine and azocine in the NGs 1 and 2 exhibited obvious antiaromatic properties.
Two nitrogen‐doped nanographenes bearing an azepine ring and an azocine ring, respectively, were synthesized and saddle‐shaped and saddle‐helix structures were obtained. Notably, two synthetic routes were adopted for the synthesis, the azepine‐embedded polyaromatic was prepared by using cyclic alkene and tetrachlorothiophene‐S,S‐dioxide instead of typical alkyne and tetraphenylcyclopenta‐2,4‐dien‐1‐one.
Multicomponent surface architectures are introduced that operate with three different dynamic covalent bonds. Disulfide exchange under basic conditions accounts for the growth of π stacks on solid ...surfaces. Hydrazone exchange under acidic conditions is used to add a second coaxial string or stack, and boronic ester exchange under neutral conditions is used to co‐align a third one. The newly introduced boronic ester exchange chemistry is compatible with stack and string exchange without interference from the orthogonal hydrazone and disulfide exchange. The functional relevance of surface architectures with three different dynamic covalent bonds is exemplified with the detection of polyphenol natural products, such as epigallocatechin gallate, in competition experiments with alizarin red. These results describe synthetic strategies to create functional systems of unprecedented sophistication with regard to dynamic covalent chemistry.
Designer architectures: Disulfide exchange under basic conditions, hydrazone exchange under acidic conditions, and boronic ester exchange at neutral pH values are combined to build multicomponent functional surface architectures using dynamic covalent chemistry. TSA/TSR=templated stack addition/release.
Designing photo‐responsive host–guest systems can provide versatile supramolecular tools for constructing smart systems and materials. We designed photo‐responsive macrocyclic hosts, modulated by ...light‐driven molecular rotary motors enabling switchable chiral guest recognition. The intramolecular cyclization of the two arms of a first‐generation molecular motor with flexible oligoethylene glycol chains of different lengths resulted in crown‐ether‐like macrocycles with intrinsic motor function. The octaethylene glycol linkage enables the successful unidirectional rotation of molecular motors, simultaneously allowing the 1:1 host–guest interaction with ammonium salt guests. The binding affinity and stereoselectivity of the motorized macrocycle can be reversibly modulated, owing to the multi‐state light‐driven switching of geometry and helicity of the molecular motors. This approach provides an attractive strategy to construct stimuli‐responsive host–guest systems and dynamic materials.
Motorized macrocycles have been successfully synthesized by combining molecular motors with crown ether macrocycles, enabling unique photo‐switchable host–guest systems controlled by the multi‐stable unidirectional rotation of molecular motors. The switchable chiral cavity can be also used for the enantioselective recognition of guests.
Bacillus subtilis ATCC 6051a is an undomesticated strain used in the industrial production of enzymes. Because it is poorly transformable, genetic manipulation in this strain requires a highly ...efficient genome editing method. In this study, a Streptococcus pyogenes CRISPR/Cas9 system consisting of an all-in-one knockout plasmid containing a target-specific guide RNA, cas9, and a homologous repair template was established for highly efficient gene disruption in B. subtilis ATCC 6051a. With an efficiency of 33% to 53%, this system was used to disrupt the srfC, spoIIAC, nprE, aprE and amyE genes of B. subtilis ATCC 6051a, which hamper its use in industrial fermentation. Compared with B. subtilis ATCC 6051a, the final mutant, BS5 (ΔsrfC, ΔspoIIAC, ΔnprE, ΔaprE, ΔamyE), produces much less foam during fermentation, displays greater resistant to spore formation, and secretes 2.5-fold more β-cyclodextrin glycosyltransferase into the fermentation medium. Thus, the CRISPR/Cas9 system proved to be a powerful tool for targeted genome editing in an industrially relevant, poorly transformable strain.
Hydrogen-Bonded Capsules in Water Zhang, Kang-Da; Ajami, Dariush; Rebek, Julius
Journal of the American Chemical Society,
12/2013, Letnik:
135, Številka:
48
Journal Article
Recenzirano
Hydrogen-bonded capsules constrain molecules into small spaces, where they exhibit behavior that is inaccessible in bulk solution. Water competes with the formation of hydrogen bonds, and other ...forces for assembly, such as metal/ligand interactions or hydrophobic effects, have been applied. Here we report the reversible assembly of a water-soluble cavitand to a robust capsule host in the presence of suitable hydrophobic guests. The complexes are characterized by conventional NMR methods. Selectivity for guest length and fluorescence quenching of a stilbene guest are used as evidence for hydrogen bonding in the capsule.
Background
Systemic inflammation and cachexia are associated with adverse clinical outcomes in elderly patients with cancer. The Geriatric Nutritional Risk Index (GNRI) is a simple and useful tool to ...assess these conditions, but its predictive ability for elderly patients with cancer cachexia (EPCC) is unknown.
Methods
This multicentre cohort study included 746 EPCC with an average age of 72.00 ± 5.24 years, of whom 489 (65.5%) were male. The patients were divided into two groups (high GNRI group ≥91.959 vs. low GNRI group <91.959) according to the optimal cut‐off value of the ROC curve. The calibration curves were performed to analyse the prognostic, predictive ability of GNRI. Comprehensive survival analyses were utilized to explore the relationship between GNRI and the overall survival (OS) of EPCC. Interaction analysis was used to investigate the comprehensive effects of low GNRI and subgroup parameters on the OS of EPCC.
Results
In this study, a total of 2560 patients were diagnosed with cancer cachexia, including 746 cases of EPCC. During the 3.6 year median follow‐up, we observed 403 deaths. The overall mortality rate for EPCC at 12 months was 34.3% (95% CI: 62.3% to 69.2%), and resulting in rate of 278 events per 1000 patient‐years. The GNRI score of EPCC was significantly lower than those of young patients with cancer cachexia (P < 0.001). The 1, 3, and 5 year calibration curves showed that the GNRI score had good survival prediction in the OS of EPCC. The GNRI could predict the OS of EPCC, whether as a continuous variable or a categorical variable. Particularly, we also found that low GNRI score (<91.959) of EPCC had a worse prognosis than those with a high GNRI score (≥91.959, P = 0.001, HR = 1.728, 95% CI: 1.244–2.401). Consistent results were observed in the tumour subgroups of gastric cancer and colorectal cancer. Notably, similar results were observed in the sensitivity analysis. In the subgroup analysis, the low GNRI has a combined effect with age (<70 years) on poor OS of EPCC. The results of the prognostic risk model found that the lower the GNRI score, the greater the prognostic risk score, and the greater the risk of death in EPCC.
Conclusions
For the first time, this study found that the GNRI score can serve as an independent prognostic factor for the OS of EPCC.
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