Successful bench‐to‐bedside translation of nanomedicine relies heavily on the development of nanocarriers with superior therapeutic efficacy and high biocompatibility. However, the optimal strategy ...for improving one aspect often conflicts with the other. Herein, we report a tactic of designing tumor‐pH‐labile linkage‐bridged copolymers of clinically validated poly(d,l‐lactide) and poly(ethylene glycol) (PEG‐Dlinkm‐PDLLA) for safe and effective drug delivery. Upon arriving at the tumor site, PEG‐Dlinkm‐PDLLA nanoparticles will lose the PEG layer and increase zeta potential by responding to tumor acidity, which significantly enhances cellular uptake and improves the in vivo tumor inhibition rate to 78.1 % in comparison to 47.8 % of the non‐responsive control. Furthermore, PEG‐Dlinkm‐PDLLA nanoparticles show comparable biocompatibility with the clinically used PEG‐b‐PDLLA micelle. The improved therapeutic efficacy and safety demonstrate great promise for our strategy in future translational studies.
PEG‐detachable delivery micelles: A chemotherapeutic vector with superior therapeutic efficacy and high biocompatibility is obtained by designing bridged PEGylated polylactide‐containing tumor‐acidity‐responsive linkages. The decreased PEGylation and increased zeta potential in the tumor matrix enhanced cellular uptake of the vector, enabling safe and effective antitumor drug delivery.
Although surface PEGylation of siRNA vectors is effective for preventing protein adsorption and thereby helps these vectors to evade the reticuloendothelial system (RES) in vivo, it also suppresses ...the cellular uptake of these vectors by target cells. This dilemma could be overcome by employing stimuli-responsive shell-detachable nanovectors to achieve enhanced cellular internalization while maintaining prolonged blood circulation. Among the possible stimuli, dysregulated pH in tumor (pHe) is the most universal and practical. However, the design of pHe-sensitive system is problematic because of the subtle differences between the pHe and pH in other tissues. Here, a simple acid-sensitive bridged copolymer is developed and used for tumor-targeted systemic delivery of siRNA. After forming the micelleplex delivery system, the corresponding nanoparticles (Dm-NP) might undergo several modifications as follows: (i) a poly(ethylene glycol) (PEG) corona, which is stable in the circulatory system and protects nanovectors from RES clearance; (ii) a pHe responsive linkage breakage, which induces PEG detachment at tumor sites and thereby facilitates cell targeting; and (iii) a cell-penetration peptide, which is exposed upon the removal of PEG and further enhances cellular uptake. Thus, Dm-NP achieved both prolonged circulation and effective accumulation in tumor cells and resulted in the safe and enhanced inhibition of non-small cell lung cancer growth.
Propane dehydrogenation (PDH) has great potential to meet the increasing global demand for propylene, but the widely used Pt‐based catalysts usually suffer from short‐term stability and ...unsatisfactory propylene selectivity. Herein, we develop a ligand‐protected direct hydrogen reduction method for encapsulating subnanometer bimetallic Pt–Zn clusters inside silicalite‐1 (S‐1) zeolite. The introduction of Zn species significantly improved the stability of the Pt clusters and gave a superhigh propylene selectivity of 99.3 % with a weight hourly space velocity (WHSV) of 3.6–54 h−1 and specific activity of propylene formation of 65.5 molC3H6
gPt−1 h−1 (WHSV=108 h−1) at 550 °C. Moreover, no obvious deactivation was observed over PtZn4@S‐1‐H catalyst even after 13000 min on stream (WHSV=3.6 h−1), affording an extremely low deactivation constant of 0.001 h−1, which is 200 times lower than that of the PtZn4/Al2O3 counterpart under the same conditions. We also show that the introduction of Cs+ ions into the zeolite can improve the regeneration stability of catalysts, and the catalytic activity kept unchanged after four continuous cycles.
A lean, mean, propylene machine: Subnanometer bimetallic Pt–Zn clusters are encapsulated inside silicalite‐1 (S‐1) zeolite via a ligand‐protected direct hydrogen reduction method. In the propane dehydrogenation (PDH) reaction, the PtZn4@S‐1‐H catalyst exhibited a very high propylene selectivity of 99.3 % and specific activity of propylene formation of 65.5 molC3H6
gPt−1 h−1 at 550 °C. Moreover, no obvious deactivation was observed over catalyst even after 13000 min on stream.
A principal goal of cancer nanomedicine is to deliver therapeutics effectively to cancer cells within solid tumors. However, there are a series of biological barriers that impede nanomedicine from ...reaching target cells. Here, we report a stimuli-responsive clustered nanoparticle to systematically overcome these multiple barriers by sequentially responding to the endogenous attributes of the tumor microenvironment. The smart polymeric clustered nanoparticle (iCluster) has an initial size of ∼100 nm, which is favorable for long blood circulation and high propensity of extravasation through tumor vascular fenestrations. Once iCluster accumulates at tumor sites, the intrinsic tumor extracellular acidity would trigger the discharge of platinum prodrug-conjugated poly(amidoamine) dendrimers (diameter ∼5 nm). Such a structural alteration greatly facilitates tumor penetration and cell internalization of the therapeutics. The internalized dendrimer prodrugs are further reduced intracellularly to release cisplatin to kill cancer cells. The superior in vivo antitumor activities of iCluster are validated in varying intractable tumor models including poorly permeable pancreatic cancer, drug-resistant cancer, and metastatic cancer, demonstrating its versatility and broad applicability.
In this forward-looking perspective, the current technologies for low-temperature waste heat recovery are first analyzed from two aspects: (i) the local waste heat recovery technology and (ii) global ...optimization of energy flow network. Based on the analysis, barriers for the further promotion of waste heat recovery are outlined, and they include the lack of global optimization methodology, distributed waste heat recovery system with high costs, and mismatches between waste heat source and demand. To address these issues, perspectives on three aspects are provided. First, advanced graphical analysis and optimization methodology integrating the heat exchange and energy conversion can promote the user-friendly optimization. Second, concentrated waste heat recovery and supply can save the investment, installation area and operation costs, thereby making the waste heat recovery cost-effective. Third, thermal storage, thermal transportation and high temperature heat pump can better couple the waste heat source and user demand from time-scale, spatial scale and energy grade, respectively. Visions for the future are combined with technical details to provide comprehensive perspectives for the next-step waste heat recovery.
•Technologies for low-temperature waste heat recovery are analyzed.•Optimizing method for combined heat exchange and conversion network is discussed.•Concentrated waste heat recovery and supply is a cost-saving option.•Technologies for the waste heat source and user demand coupling are discussed.
Tomato bacterial wilt caused by Ralstonia solanacearum bacterium is a severe problem in Southern China, where relatively high environmental temperatures commonly prevails during the crop seasons. ...Previous research has indicated that bacterial wilt disease incidence generally increases during the warm months of summer leading to reduced tomato yield. Moreover, the efficacy of bio-organic fertilizers (BOFs)-organic compost fortified with pathogen-suppressive bacteria-is often lost during the periods of high environmental temperatures. Here we studied if the disease incidence could be reduced and the BOF performance enhanced by simply preponing and postponing the traditional seedling transplantation times to avoid tomato plant development during periods of high environmental temperature. To this end, a continuous, two-year field experiment was conducted to evaluate the performance of BOF in two traditional (late-spring LS and early-autumn EA) and two alternative (early-spring ES and late-autumn LA) crop seasons. We found that changing the transplantation times reduced the mean disease incidence from 33.9% (LS) and 54.7% (EA) to 11.1% (ES) and 7.1% (LA), respectively. Reduction in disease incidence correlated with the reduction in R. Solanacearum pathogen density in the tomato plant rhizosphere and stem base. Applying BOF during alternative transplantation treatments improved biocontrol efficiency from 43.4% (LS) and 3.1% (EA) to 67.4% (ES) and 64.8% (LA). On average, the mean maximum air temperatures were positively correlated with the disease incidence, and negatively correlated with the BOF biocontrol efficacy over the crop seasons. Crucially, even though preponing the transplantation time reduced the tomato yield in general, it was still economically more profitable compared to LS season due to reduced crop losses and relatively higher market prices. Preponing and postponing traditional tomato transplantation times to cooler periods could thus offer simple but effective way to control R. solanacearum disease outbreaks.
DNA methylation is the predominant epigenetic modification that participates in many fundamental cellular processes through posttranscriptional regulation of gene expression. Aberrant DNA methylation ...is closely associated with a variety of human diseases including cancers. Therefore, accurate and sensitive detection of DNA methylation may greatly facilitate the epigenetic biological researches and disease diagnosis. In recent years, a series of novel biosensors have been developed for highly sensitive detection of DNA methylation, but an overview of recent advances in biosensors for in vitro detection and especially live-cell imaging of DNA methylation is absent. In this review, we summarize the emerging biosensors for in vitro and in vivo DNA methylation assays in the past five years (2015–2020). Based on the signal types, the biosensors for in vitro DNA methylation assay are classified into five categories including fluorescent, electrochemical, colorimetric, surface enhanced Raman spectroscopy, mass spectrometry, and surface plasmon resonance biosensors, while the biosensors for in vivo DNA methylation assay mainly rely on fluorescent imaging. We review the strategies, features and applications of these biosensors, and provide a new insight into the challenges and future directions in this area.
1.We reviewed the recent advances in biosensors for in vitro detection and in vivo imaging of DNA methylation.2.Biosensors for in vitro DNA methylation assay are classified into five categories.3.Biosensors for in vivo DNA methylation assay mainly rely on fluorescent imaging.4.The strategies, features and applications of these biosensors are highlighted.5.The challenges and future directions in this area are discussed.
In order to improve the position high-precision synchronization performance of multi-motor synchronous control, a multi-motor position synchronization control method based on non-singular fast ...terminal sliding mode control (NFTSMC) combined with an improved deviation coupling control structure (Improved Deviation Coupling Control(IDCC), NFTSMC+IDCC). Firstly, this paper designs a sliding mode controller using a non-singular fast terminal sliding mode surface with a Permanent Magnet Synchronous Motor (PMSM) as the control object. Secondly, the deviation coupling is improved to enhance the coupling between multiple motors and achieve position synchronization. Finally, the simulation results show that the total error of multi-motor position synchronization under NFTSMC control is 0.553r in the simulation of multi-motor synchronization control under the same working conditions, which is 2.873r and 1.772r less than that of SMC and FTSMC in terms of speed error, and the anti-disturbance performance is 83.68% and 76.22% higher than that of both of them, respectively. In the subsequent simulation of the improved multi-motor position synchronization structure, the total error of the multi-motor position is in the range of 0.56r-0.58r at three speeds, which is much smaller than the synchronization error under the Ring Coupling Control (RCC) structure and Deviation Coupling Control (DCC) structure, showing a better The synchronization error is much smaller than that of the RCC structure and DCC structure, which shows better position synchronization performance. Therefore, the multi-motor position synchronization control method proposed in this paper has a good position synchronization effect and achieves the control effect of small displacement error and fast convergence of the multi-motor position synchronization control system after being disturbed, the control performance is significantly improved.
Bacterial communities associated with plant roots play an important role in the suppression of soil-borne pathogens, and multispecies probiotic consortia may enhance disease suppression efficacy. ...Here we introduced defined Pseudomonas species consortia into naturally complex microbial communities and measured the importance of Pseudomonas community diversity for their survival and the suppression of the bacterial plant pathogen Ralstonia solanacearum in the tomato rhizosphere microbiome. The survival of introduced Pseudomonas consortia increased with increasing diversity. Further, high Pseudomonas diversity reduced pathogen density in the rhizosphere and decreased the disease incidence due to both intensified resource competition and interference with the pathogen. These results provide novel mechanistic insights into elevated pathogen suppression by diverse probiotic consortia in naturally diverse plant rhizospheres. Ecologically based community assembly rules could thus play a key role in engineering functionally reliable microbiome applications.
The increasing demand for food supply requires more-efficient control of plant diseases. The use of probiotics, i.e., naturally occurring bacterial antagonists and competitors that suppress pathogens, has recently reemerged as a promising alternative to agrochemical use. It is, however, still unclear how many and which strains we should choose for constructing effective probiotic consortia. Here we present a general ecological framework for assembling effective probiotic communities based on in vitro characterization of community functioning. Specifically, we show that increasing the diversity of probiotic consortia enhances community survival in the naturally diverse rhizosphere microbiome, leading to increased pathogen suppression via intensified resource competition and interference with the pathogen. We propose that these ecological guidelines can be put to the test in microbiome engineering more widely in the future.
Human genetic and genomic studies have supported a strong causal role of
deficiency in autism spectrum disorder (ASD). However, the molecular mechanism underlying
deficiency resulting in ASD is not ...fully understood. Recently, the zebrafish has become an attractive organism to model ASD because of its high efficiency of genetic manipulation and robust behavioral phenotypes. The orthologous gene to human
is duplicated in the zebrafish genome and has two homologs,
and
. Previous studies have reported
morphants in zebrafish using the morpholino method. Here, we report the generation and characterization of
mutant zebrafish in larval and adult stages using the CRISPR/Cas9 genome editing technique.
CRISPR/Cas9 was applied to generate a
loss-of-function mutation (
) in zebrafish. A series of morphological measurements, behavioral tests, and molecular analyses were performed to systematically characterize the behavioral and molecular changes in
mutant zebrafish.
zebrafish exhibited abnormal morphology in early development. They showed reduced locomotor activity both as larvae and adults, reduced social interaction and time spent near conspecifics, and significant repetitive swimming behaviors. Additionally, the levels of both postsynaptic homer1 and presynaptic synaptophysin were significantly reduced in the adult brain of
deficient zebrafish.
We generated the first inheritable
mutant zebrafish model using CRISPR/Cas9 gene editing approach.
zebrafish displayed robust autism-like behaviors and altered levels of the synaptic proteins homer1 and synaptophysin. The versatility of zebrafish as a model for studying neurodevelopment and conducting drug screening will likely have a significant contribution to future studies of human
function and ASD.
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