The rapid development of CRISPR/Cas9 systems has opened up tantalizing prospects to sensitize cancers to chemotherapy using efficient targeted genome editing, but safety concerns and possible ...off-target effects of viral vectors remain a major obstacle for clinical application. Thus, the construction of novel nonviral tumor-targeting nanodelivery systems has great potential for the safe application of CRISPR/Cas9 systems for gene-chemo-combination therapy. Here, we report a polyamidoamine-aptamer-coated hollow mesoporous silica nanoparticle for the co-delivery of sorafenib and CRISPR/Cas9. The core-shell nanoparticles had good stability, enabled ultrahigh drug loading, targeted delivery, and controlled-release of the gene-drug combination. The nanocomplex showed >60% EGFR-editing efficiency without off-target effects in all nine similar sites, regulating the EGFR-PI3K-Akt pathway to inhibit angiogenesis, and exhibited a synergistic effect on cell proliferation. Importantly, the co-delivery nanosystem achieved efficient EGFR gene therapy and caused 85% tumor inhibition in a mouse model. Furthermore, the nanocomplex showed high accumulation at the tumor site
and exhibited good safety with no damage to major organs. Due to these properties, the nanocomplex provides a versatile delivery approach for efficient co-loading of gene-drug combinations, allowing for precise gene editing and synergistic inhibition of tumor growth without apparent side effects on normal tissues.
Prodrug activation, by exogenously administered enzymes, for cancer therapy is an approach to achieve better selectivity and less systemic toxicity than conventional chemotherapy. However, the short ...half‐lives of the activating enzymes in the bloodstream has limited its success. Demonstrated here is that a tyrosinase‐MOF nanoreactor activates the prodrug paracetamol in cancer cells in a long‐lasting manner. By generating reactive oxygen species (ROS) and depleting glutathione (GSH), the product of the enzymatic conversion of paracetamol is toxic to drug‐resistant cancer cells. Tyrosinase‐MOF nanoreactors cause significant cell death in the presence of paracetamol for up to three days after being internalized by cells, while free enzymes totally lose activity in a few hours. Thus, enzyme‐MOF nanocomposites are envisioned to be novel persistent platforms for various biomedical applications.
Covert delivery: Demonstrated here is activation of the prodrug paracetamol, by a tyrosinase‐MOF nanoreactor, in cancer cells in a long‐lasting manner. By generating reactive oxygen species and depleting glutathione, the product of the enzymatic conversion of paracetamol is toxic to drug‐resistant cancer cells. Tyrosinase‐MOF nanoreactors cause significant cell death in the presence of paracetamol for up to three days after being internalized by cells, while free enzymes lose activity in a few hours. MOF=metal–organic framework.
This paper quantifies the impact of correlated fading on secure communication of multiple amplify-and-forward (AF) relaying networks. In such a network, the base station (BS) is equipped with ...multiple antennas and communicates with the destination through multiple AF relays, while the message from the relays can be overheard by an eavesdropper. We focus on the practical communication scenario, where the main and eavesdropper's channels are correlated. In order to enhance the transmission security, transmit antenna selection is performed at the BS, and the best relay is chosen according to the full- or partial-relay selection criterion, which relies on the dual-hop relay channels or the second-hop relay channels, respectively. For these criteria, we study the impact of correlated fading on the network secrecy performance, by deriving an analytical approximation for the secrecy outage probability and an asymptotic expression for the high main-to-eavesdropper ratio. From these results, it is concluded that the channel correlation is always beneficial to the secrecy performance of full relay selection. However, it deteriorates the secrecy performance if partial-relay selection is used, when the number of antennas at the BS is less than the number of relays.
SUMMARY
Rhodiola L. is a genus that has undergone rapid radiation in the mid‐Miocene and may represent a typic case of adaptive radiation. Many species of Rhodiola have also been widely used as an ...important adaptogen in traditional medicines for centuries. However, a lack of high‐quality chromosome‐level genomes hinders in‐depth study of its evolution and biosynthetic pathway of secondary metabolites. Here, we assembled two chromosome‐level genomes for two Rhodiola species with different chromosome number and sexual system. The assembled genome size of R. chrysanthemifolia (2n = 14; hermaphrodite) and R. kirilowii (2n = 22; dioecious) were of 402.67 and 653.62 Mb, respectively, with approximately 57.60% and 69.22% of transposable elements (TEs). The size difference between the two genomes was mostly due to proliferation of long terminal repeat‐retrotransposons (LTR‐RTs) in the R. kirilowii genome. Comparative genomic analysis revealed possible gene families responsible for high‐altitude adaptation of Rhodiola, including a homolog of plant cysteine oxidase 2 gene of Arabidopsis thaliana (AtPCO2), which is part of the core molecular reaction to hypoxia and contributes to the stability of Group VII ethylene response factors (ERF‐VII). We found extensive chromosome fusion/fission events and structural variations between the two genomes, which might have facilitated the initial rapid radiation of Rhodiola. We also identified candidate genes in the biosynthetic pathway of salidroside. Overall, our results provide important insights into genome evolution in plant rapid radiations, and possible roles of chromosome fusion/fission and structure variation played in rapid speciation.
Significance Statement
We assembled two chromosome‐level genomes for two Rhodiola species with different chromosome number and sexual system. Comparative genomic analyses demonstrated extensive chromosome fusion/fissions and structural variations between the two genomes, which might have played a role in rapid establishment of post‐zygotic reproductive isolation, facilitating the initial rapid radiation of Rhodiola. Possible gene families responsible for high‐altitude adaptation and the salidroside biosynthesis pathway were identified, and the salidroside biosynthesis pathway might evolve in a stepwise manner in Rhodiola.
All-solid-state ionic supercapacitors based ceramic oxides exhibit better characteristics than the conventional liquid-electrolyte supercapacitors in terms of high safety and broad working potential. ...However, there are rare reports referring to the working mechanism as well as factors impacting the capacities of these solid- state supercapacitors. In this work, Li3xLa2/3-x□1/3-2xTiO3 (LLTO, □ represents vacancy) materials with different lithium contents (nominal 3x = 0.33∼0.42) are synthesized and fabricated into solid-state supercapacitors, to study the capacity. Results exhibit that the Li0.33La0.56TiO3 can release the highest capacitance of 0.28 m F⋅ g−1 among the samples with superior cycling performance under a potential range of 2 V at 300 K, based on an Au∣LLTO∣Au cell configuration. The possible factors to affect the capacity include the lattice structures, ionic conductivity, and working temperature. This study may provide new insights into the design of more stable energy storage devices with better safety.
•Umbrella review of 20 outcomes in 17 systematic reviews and meta-analyses.•Tomato intake benefited mortality, prostate cancer, and gastric cancer.•Lycopene benefited mortality, prostate cancer, CVD, ...and metabolic syndrome.•Caution was warranted for potential allergy and pollution.•But the quality of the evidence was not high.
Lycopene is a potent lipophilic antioxidant in tomato. We aim to clarify the evidence for associations between tomato and lycopene and multiple health outcomes. Umbrella review of meta-analyses and systematic reviews was performed in humans. A total of 174 articles were searched, 17 articles with 20 health outcomes were identified by eligibility criteria. Tomato intake was inversely associated with all-cause mortality, coronary heart disease mortality, cerebrovascular disease mortality, prostate cancer, and gastric cancer. Dietary lycopene intake or serum lycopene was inversely associated with all-cause mortality, prostate cancer, stroke, cardiovascular disease, metabolic syndrome, and male infertility. Caution was warranted for potential allergy and pollution. The quality of the vast majority of evidence by GRADE was low or very low with the remaining six as moderate. The intake of tomato or lycopene was generally safe and beneficial for multiple health outcomes in humans. But the quality of the evidence was not high.
Whether the dynamic change of neutrophil to lymphocyte ratio (delta-NLR) can predict the outcome in various malignancies remained controversial. The delta-NLR has not been evaluated in colon cancer. ...Thus, we conducted the study to evaluate the predictive value of the delta-NLR in patients with colon cancer who underwent curative resection. Three-hundred and fifty-four patients with stage I-III colon cancer were retrospectively analysed. Clinicopathological features, preoperative NLR and postoperative NLR were collected. Prognostic factors were evaluated by univariate and multivariate analysis. The one, three and five-year overall survival rate in the delta-NLR < 0 group was 98.2%, 90.7% and 83.6%, respectively; and in the delta-NLR ≥ 0 group was 98.4%, 96.9% and 95.3%, respectively (log-rank test, P = 0.002). Univariate and multivariate analysis showed that there was a strong relationship between delta-NLR and overall survival. In conclusion, the delta-NLR was an independent prognostic factor for overall survival in early stage colon cancer. Patients with increased delta-NLR had an favourable clinical outcome.
Abstract
In this work, commercial anatase TiO
2
powders were modified using ultrathin Fe
2
O
3
layer by atomic layer deposition (ALD). The ultrathin Fe
2
O
3
coating having small bandgap of 2.20 eV ...can increase the visible light absorption of TiO
2
supports, at the meantime, Fe
2
O
3
/TiO
2
heterojunction can effectively improve the lifetime of photogenerated electron–hole pairs. Results of ALD Fe
2
O
3
modified TiO
2
catalyst, therefore, showed great visible light driven catalytic degradation of methyl orange compared to pristine TiO
2
. A 400 cycles of ALD Fe
2
O
3
(~ 2.6 nm) coated TiO
2
powders exhibit the highest degradation efficiency of 97.4% in 90 min, much higher than pristine TiO
2
powders of only 12.5%. Moreover, an ultrathin ALD Al
2
O
3
(~ 2 nm) was able to improve the stability of Fe
2
O
3
-TiO
2
catalyst. These results demonstrate that ALD surface modification with ultrathin coating is an extremely powerful route for the applications in constructing efficient and stable photocatalysts.
One of the most important ecological processes is the formation of interspecific relationships in relation to spatial patterns among alpine cushion plants in extreme environmental habitats. However, ...such relationships remain poorly understood. Here, we examined the spatial patterns of alpine cushion plants along an altitudinal gradient of environmental severity and the interspecific relationship between two cushion species (
Thylacospermum caespitosum
and
Androsace tangulashanensis
) on the eastern Kunlun Mountain of China. Our results showed that the two species were highly aggregated within a distance of 2.5–5 m at the mid (S2) altitude, whereas they were randomly distributed at the low (S1) and high (S3) altitudes. A positive spatial interaction between the two species was observed over shorter distances at the mid (S2) altitude, and the spatial patterns were related to the size of individuals of the two species. Moreover, the impact of
A. tangulashanensis
on
T. caespitosum
(RII
T. caespitosum
) was negative in all the study plots, and a positive impact of
T. caespitosum
on
A. tangulashanensis
(RII
A. tangulashanensis
) was only observed at the mid (S2) altitude. Together, these results demonstrated that the spatial patterns of these two cushions varied with environmental severity, since the outcome of the interactions were different, to some extent, at the three altitudes. Plant size is the main factor affecting the spatial correlation and interspecific relationship between two cushions. Therefore, its potential influence should be considered when discussing interspecific relationships among cushions and their community construction at small scales in alpine ecosystems.
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