Targeting a mTOR/autophagy axis: a double-edged sword of rapamycin in spontaneous miscarriage.

Immune dysfunction is a primary culprit behind spontaneous miscarriage (SM). To address this, immunosuppressive agents have emerged as a novel class of tocolytic drugs, modulating the maternal immune system's tolerance towards the embryo. Rapamycin (PubChem CID:5284616), a dual-purpose compound, functions as an immunosuppressive agent and triggers autophagy by targeting the mTOR pathway. Its efficacy in treating SM has garnered significant research interest in recent times. Autophagy, the cellular process of self-degradation and recycling, plays a pivotal role in numerous health conditions. Research indicates that autophagy is integral to endometrial decidualization, trophoblast invasion, and the proper functioning of decidual immune cells during a healthy pregnancy. Yet, in cases of SM, there is a dysregulation of the mTOR/autophagy axis in decidual stromal cells or immune cells at the maternal-fetal interface. Both in vitro and in vivo studies have highlighted the potential benefits of low-dose rapamycin in managing SM. However, given mTOR's critical role in energy metabolism, inhibiting it could potentially harm the pregnancy. Moreover, while low-dose rapamycin has been deemed safe for treating recurrent implant failure, its potential teratogenic effects remain uncertain due to insufficient data. In summary, rapamycin represents a double-edged sword in the treatment of SM, balancing its impact on autophagy and immune regulation. Further investigation is warranted to fully understand its implications.

Altered Neuromagnetic Activity in the Default Mode Network in Migraine and Its Subgroups (Episodic Migraine and Chronic Migraine).

BACKGROUND: The differences in the resting state spectral power and functional connectivity of the default mode network between people with migraine without aura (MwoA) and its subgroups differentiated by frequency (episodic migraine (EM) and chronic migraine (CM)) and healthy controls (HC) were investigated using magnetoencephalography. METHODS: In the resting state, the topological spatial structure of the brain in 33 MwoA patients and 22 HC was first studied using magnetoencephalography, followed by probing the neuroelectrical activity of 17 CM and 16 EM patients, to identify damage to their default mode network (DMN). The techniques used to investigate both spectral power and functional connectivity were minimum-paradigm estimation combined with Welch's technique and corrected amplitude envelope correlation. RESULTS: The differences between MwoA and its subgroups (CM and EM) and HC based on spectral power were mainly in the delta, theta, and alpha bands, while the differences in functional connectivity were primarily in the delta, alpha, and beta bands. In the delta and theta bands, the spectral power of MwoA and its subgroups (CM and EM) was higher than in the HC group. The spectral power of MwoA and its subgroups (CM and EM) was lower in the alpha band. In terms of functional connectivity, the corrected amplitude envelope correlation of MwoA and its subgroups (CM and EM) was lower than the HC group in the bands with spectral differences. People with EM and CM differed in the spectral power in the left medial prefrontal cortex and the right lateral temporal cortex in the alpha band, where correlation analysis and logistic regression analysis showed that the intensity of the spectral power of the left medial prefrontal cortex was negatively correlated with headache frequency. CONCLUSIONS: The spectral power of the left medial prefrontal cortex in the alpha band may serve as a biomarker that is associated with the number of monthly headache attacks and may be a potential neuromodulatory target for controlling migraine chronicity.

Editing of ORF138 restores fertility of Ogura cytoplasmic male sterile broccoli via mitoTALENs.

Cytoplasmic male sterility (CMS), encoded by the mitochondrial open reading frames (ORFs), has long been used to economically produce crop hybrids. However, the utilization of CMS also hinders the exploitation of sterility and fertility variation in the absence of a restorer line, which in turn narrows the genetic background and reduces biodiversity. Here, we used a mitochondrial targeted transcription activator-like effector nuclease (mitoTALENs) to knock out ORF138 from the Ogura CMS broccoli hybrid. The knockout was confirmed by the amplification and re-sequencing read mapping to the mitochondrial genome. As a result, knockout of ORF138 restored the fertility of the CMS hybrid, and simultaneously manifested a cold-sensitive male sterility. ORF138 depletion is stably inherited to the next generation, allowing for direct use in the breeding process. In addition, we proposed a highly reliable and cost-effective toolkit to accelerate the life cycle of fertile lines from CMS-derived broccoli hybrids. By applying the k-mean clustering and interaction network analysis, we identified the central gene networks involved in the fertility restoration and cold-sensitive male sterility. Our study enables mitochondrial genome editing via mitoTALENs in Brassicaceae vegetable crops and provides evidence that the sex production machinery and its temperature-responsive ability are regulated by the mitochondria.

Interictal magnetic signals in new-onset Rolandic epilepsy may help with timing of treatment selection.

OBJECTIVE: With research progress on Rolandic epilepsy (RE), its "benign" nature has been phased out. Clinicians are exhibiting an increasing tendency toward a more assertive treatment approach for RE. Nonetheless, in clinical practice, delayed treatment remains common because of the "self-limiting" nature of RE. Therefore, this study aimed to identify an imaging marker to aid treatment decisions and select a more appropriate time for initiating therapy for RE. METHODS: We followed up with children newly diagnosed with RE, classified them into medicated and non-medicated groups according to the follow-up results, and compared them with matched healthy controls. Before beginning follow-up visits, interictal magnetic data were collected using magnetoencephalography in treatment-naïve recently diagnosed patients. The spectral power of the whole brain during initial diagnosis was determined using minimum normative estimation combined with the Welch technique. RESULTS: A difference was observed in the magnetic source intensity within the left caudal anterior cingulate and precentral and postcentral gyri in the delta band between the medicated and non-medicated groups. The results revealed good discriminatory ability within the receiver operator characteristic curve. In the medicated group, there was a specific change in the frontotemporal magnetic source intensity, which shifted from high to low frequencies, compared with the healthy control group. SIGNIFICANCE: The intensity of the precentral gyrus magnetic source within the delta band showed good specificity. Considering the rigor of initial treatment, the intensity of the precentral gyrus magnetic source can provide some help as an imaging marker for initial RE treatment, particularly for the timing of treatment initiation.

A phosphoinositide switch mediates exocyst recruitment to multivesicular endosomes for exosome secretion.

Exosomes are secreted to the extracellular milieu when multivesicular endosomes (MVEs) dock and fuse with the plasma membrane. However, MVEs are also known to fuse with lysosomes for degradation. How MVEs are directed to the plasma membrane for exosome secretion rather than to lysosomes is unclear. Here we report that a conversion of phosphatidylinositol-3-phosphate (PI(3)P) to phosphatidylinositol-4-phosphate (PI(4)P) catalyzed sequentially by Myotubularin 1 (MTM1) and phosphatidylinositol 4-kinase type IIα (PI4KIIα) on the surface of MVEs mediates the recruitment of the exocyst complex. The exocyst then targets the MVEs to the plasma membrane for exosome secretion. We further demonstrate that disrupting PI(4)P generation or exocyst function blocked exosomal secretion of Programmed death-ligand 1 (PD-L1), a key immune checkpoint protein in tumor cells, and led to its accumulation in lysosomes. Together, our study suggests that the PI(3)P to PI(4)P conversion on MVEs and the recruitment of the exocyst direct the exocytic trafficking of MVEs for exosome secretion.

Ginsenosides in endometrium-related diseases: Emerging roles and mechanisms.

Ginsenosides, agents extracted from an important herb (ginseng), are expected to provide new therapies for endometrium-related diseases. Based on the molecular types of ginsenosides, we reviewed the main pharmacological effects of ginsenosides against endometrium-related diseases (e.g., endometrial cancers, endometriosis, and endometritis). The mechanism of action of ginsenosides involves inducing apoptosis of endometrium-related cells, promoting autophagy of endometrium-related cells, regulating epithelial-mesenchymal transition (EMT) in endometrium-related cells, and activating the immune system to kill cells associated with endometrial diseases. We hope to provide a theoretical foundation for the treatment of endometrium-related diseases by ginsenosides.

Variation in functional networks between clinical and subclinical discharges in childhood absence epilepsy: A multi-frequency MEG study.

OBJECTIVE: Two types of spike-and-wave discharges (SWDs) exist in childhood absence epilepsy (CAE): clinical discharges are prolonged and manifest primarily as impaired consciousness, whereas subclinical discharges are brief with few objectively visible symptoms. This study aimed to compare neural functional network and default mode network (DMN) activity between clinical and subclinical discharges to better understand the underlying mechanism of CAE. METHODS: Using magnetoencephalography (MEG) data from 21 patients, we obtained 25 segments each of clinical discharges and subclinical discharges. Amplitude envelope correlation analysis was used to construct functional networks and graph theory was used to calculate network topological data. We then compared differences in functional connectivity within the DMN between clinical and subclinical discharges. All statistical comparisons were performed using paired-sample tests. RESULTS: Compared to subclinical discharges, the functional network of clinical discharges exhibited higher synchronization - particularly in the parahippocampal gyrus - as early as 10 s before the seizure. Additionally, the functional network of clinical SWDs presented an anterior shift of key nodes in the alpha frequency band. Regarding clinical discharge progression, there were gradual increases in the parameter node strengths (S), clustering coefficients (C), and global efficiency (E) of the functional networks, while the path lengths (L) decreased. These changes were most prominent at the onset of discharges and followed by some recovery in the high-frequency bands, but no significant change in the low-frequency bands. Furthermore, connections within the DMN during the discharge period were significantly stronger for clinical discharge compared to subclinical discharges. CONCLUSIONS: These findings suggest that a more regular network before abnormal discharges in clinical discharges contributes to SWD explosion and that the parahippocampal gyrus plays an important role in maintaining oscillations. An absence seizure is a gradual process and the emergence of SWDs may be accompanied by initiation of inhibitory mechanisms. Enhanced functional connectivity among DMN brain regions may indicate that patients have entered a state of introspection, and functional abnormalities in the parahippocampal gyrus may be associated with patients' transient memory loss.

Language-related brain areas in childhood epilepsy with centrotemporal spikes studied with MEG.

OBJECTIVE: Children with self-limited epilepsy with centrotemporal spikes (SeLECTS) typically indicate cognitive impairment with widespread speech impairment. We explored how epilepsy affects language-related brain areas and areas in their vicinity. METHODS: Twenty-two children with SeLECTS and declined verbal comprehension (DVC), 21 with SeLECTS and normal verbal comprehension (NVC), and 23 healthy controls (HCs) underwent high-sampling magnetoencephalography recordings. According to a previous study, 24 language-related regions of interest were selected bilaterally, and the relative spectral power was estimated using a minimum norm estimate. RESULTS: The highest mean power spectral density was observed in the delta band for the DVC group, in the theta band for the NVC group, and in the alpha band for HCs within language-specific brain regions. The distinctions between the DVC and NVC groups in the delta and theta frequency bands were primarily concentrated in the right linguistic brain area. CONCLUSIONS: Children with SeLECTS may have developmental problems in language-related brain areas, with different developmental levels observed in the DVC, NVC, and HC groups. The DVC group could have inferior speech comprehension due to a more significant number of seizures and more left-sided spike locations. SIGNIFICANCE: Children having SeLECTS showed impaired brain maturation, leading to associated language impairment.

Impact of interictal epileptiform discharges on brain network in self-limited epilepsy with centrotemporal spikes: A magnetoencephalography study.

OBJECTIVE: This study aimed to investigate the differences on resting-state brain networks between the interictal epileptiform discharge (IED) group with self-limited epilepsy with centrotemporal spikes (SeLECTS), the non-IED group with SeLECTS, and the healthy control (HC) group. METHODS: Patients were divided into the IED and non-IED group according to the presence or absence of IED during magnetoencephalography (MEG). We used Wechsler Intelligence Scale for Children, fourth edition (WISC-IV) to assess cognition in 30 children with SeLECTS and 15 HCs. Functional networks were constructed at the whole-brain level and graph theory (GT) analysis was used to quantify the topology of the brain network. RESULTS: The IED group had the lowest cognitive function scores, followed by the non-IED group and then HCs. Our MEG results showed that the IED group had more dispersed functional connectivity (FC) in the 4-8 Hz frequency band, and more brain regions were involved compared to the other two groups. Furthermore, the IED group had fewer FC between the anterior and posterior brain regions in the 12-30 Hz frequency band. Both the IED group and the non-IED group had fewer FC between the anterior and posterior brain regions in the 80-250 Hz frequency band compared to the HC group. GT analysis showed that the IED group had a higher clustering coefficient compared to the HC group and a higher degree compared to the non-IED group in the 80-250 Hz frequency band. The non-IED group had a lower path length in the 30-80 Hz frequency band compared to the HC group. CONCLUSIONS: The study data obtained in this study suggested that intrinsic neural activity was frequency-dependent and that FC networks of the IED group and the non-IED group underwent changes in different frequency bands. These network-related changes may contribute to cognitive dysfunction in children with SeLECTS.

Altered neuromagnetic activity in default mode network in childhood absence epilepsy.

Purpose: The electrophysiological characterization of resting state oscillatory functional connectivity within the default mode network (DMN) during interictal periods in childhood absence epilepsy (CAE) remains unclear. Using magnetoencephalographic (MEG) recordings, this study investigated how the connectivity within the DMN was altered in CAE. Methods: Using a cross-sectional design, we analyzed MEG data from 33 children newly diagnosed with CAE and 26 controls matched for age and sex. The spectral power and functional connectivity of the DMN were estimated using minimum norm estimation combined with the Welch technique and corrected amplitude envelope correlation. Results: Default mode network showed stronger activation in the delta band during the ictal period, however, the relative spectral power in other bands was significantly lower than that in the interictal period (p corrected < 0.05 for DMN regions, except bilateral medial frontal cortex, left medial temporal lobe, left posterior cingulate cortex in the theta band, and the bilateral precuneus in the alpha band). It should be noted that the significant power peak in the alpha band was lost compared with the interictal data. Compared with controls, the interictal relative spectral power of DMN regions (except bilateral precuneus) in CAE patients was significantly increased in the delta band (p corrected < 0.01), whereas the values of all DMN regions in the beta-gamma 2 band were significantly decreased (p corrected < 0.01). In the higher frequency band (alpha-gamma1), especially in the beta and gamma1 band, the ictal node strength of DMN regions except the left precuneus was significantly higher than that in the interictal periods (p corrected < 0.01), and the node strength of the right inferior parietal lobe increased most significantly in the beta band (Ictal: 3.8712 vs. Interictal: 0.7503, p corrected < 0.01). Compared with the controls, the interictal node strength of DMN increased in all frequency bands, especially the right medial frontal cortex in the beta band (Controls: 0.1510 vs. Interictal: 3.527, p corrected < 0.01). Comparing relative node strength between groups, the right precuneus in CAE children decreased significantly (ß: Controls: 0.1009 vs. Interictal: 0.0475; γ 1: Controls:0.1149 vs. Interictal:0.0587, p corrected < 0.01) such that it was no longer the central hub. Conclusion: These findings indicated DMN abnormalities in CAE patients, even in interictal periods without interictal epileptic discharges. Abnormal functional connectivity in CAE may reflect abnormal anatomo-functional architectural integration in DMN, as a result of cognitive mental impairment and unconsciousness during absence seizure. Future studies are needed to examine if the altered functional connectivity can be used as a biomarker for treatment responses, cognitive dysfunction, and prognosis in CAE patients.

The coiled-coil protein gene WPRb confers recessive resistance to Cucumber green mottle mosaic virus.

Cucumber green mottle mosaic virus (CGMMV) is one of the major global quarantine viruses and causes severe symptoms in Cucurbit crops, particularly with regard to fruit decay. However, the genetic mechanisms that control plant resistance to CGMMV have yet to be elucidated. Here, we found that WPRb, a weak chloroplast movement under blue light 1 and plastid movement impaired 2-related protein family gene, is recessively associated with CGMMV resistance in watermelon (Citrullus lanatus). We developed a reproducible marker based on a single non-synonymous substitution (G1282A) in WPRb, which can be used for marker-assisted selection for CGMMV resistance in watermelon. Editing of WPRb conferred greater tolerance to CGMMV. We found WPRb targets to the plasmodesmata (PD) and biochemically interacts with the CGMMV movement protein, facilitating viral intercellular movement by affecting the permeability of PD. Our findings enable us to genetically control CGMMV resistance in planta by using precise genome editing techniques targeted to WPRb.

Hormone-Glutamine Metabolism: A Critical Regulatory Axis in Endocrine-Related Cancers.

The endocrine-related cancers and hormones are undoubtedly highly interconnected. How hormones support or repress tumor induction and progression has been extensively profiled. Furthermore, advances in understanding the role of glutamine metabolism in mediating tumorigenesis and development, coupled with these in-depth studies on hormone (e.g., estrogen, progesterone, androgen, prostaglandin, thyroid hormone, and insulin) regulation of glutamine metabolism, have led us to think about the relationship between these three factors, which remains to be elucidated. Accordingly, in this review, we present an updated overview of glutamine metabolism traits and its influence on endocrine oncology, as well as its upstream hormonal regulation. More importantly, this hormone/glutamine metabolism axis may help in the discovery of novel therapeutic strategies for endocrine-related cancer.

IL-27 promotes decidualization via the STAT3-ESR/PGR regulatory axis.

Appropriate decidualization is of great importance for embryo implantation, placental development and successful pregnancy. Although it has been well-acknowledged that decidualization relies on activation of progesterone-mediated signaling pathway, the exact mechanisms have not been elucidated. Here, we demonstrated that both IL-27 and IL27RA were highly expressed in decidua than those in endometrium during secretory phase. Estrogen plus progesterone significantly upregulated the expression of IL-27 and IL-27RA in endometrium stromal cells (ESCs). In addition, inhibiting IL-27 signaling with IL-27 neutralization antibody (anti-IL-27) suppressed the expression of decidualization-related molecules, receptors of estrogen (gene coded by ESR) and progesterone (PGR) induced by cAMP or estrogen plus progesterone. Similar results were obtained from Il27ra-/- (knockout of Il27ra) female mice. Moreover, knockout of Il27ra did not affect the estrus cycle and folliculogenesis in mice but reduced implantation rate with the impairing decidualization. Mechanistically, IL-27 upregulated the expression of ESR1, ESR2 and PGR in ESCs and DSCs, as well as the phosphorylation level of STAT3. In the presence of estrogen plus progesterone, treatment with ESCs with anti-IL-27 inhibited the activation of STAT3. Also, the expression of ESR, PGR was decreased in Il27ra-/- mice. In conclusion, these findings demonstrate that IL-27 upregulated by estrogen and progestogen promotes decidualization possibly through a STAT3-dominant pathway.

Exploiting sterility and fertility variation in cytoplasmic male sterile vegetable crops.

Cytoplasmic male sterility (CMS) has long been used to economically produce hybrids that harness growth vigor through heterosis. Yet, how CMS systems operate within commercially viable seed production strategies in various economically important vegetable crops, and their underlying molecular mechanisms, are often overlooked details that could expand the utility of CMS as a cost-effective and stable system. We provide here an update on the nature of cytoplasmic-nuclear interplay for pollen sterility and fertility transitions in vegetable crops, based on the discovery of components of nuclear fertility restoration and reversion determinants. Within plant CMS systems, pollen fertility can be rescued by the introduction of nuclear fertility restorer genes (Rfs), which operate by varied mechanisms to countermand the sterility phenotype. By understanding these systems, it is now becoming feasible to achieve fertility restoration with Rfs designed for programmable CMS-associated open reading frames (ORFs). Likewise, new opportunities exist for targeted disruption of CMS-associated ORFs by mito-TALENs in crops where natural Rfs have not been readily identified, providing an alternative approach to recovering fertility of cytoplasmic male sterile lines in crops. Recent findings show that facultative gynodioecy, as a reproductive strategy, can coordinate the sterility and fertility transition in response to environmental cues and/or metabolic signals that reflect ecological conditions of reproductive isolation. This information is important to devising future systems that are more inherently stable.

Convenient Genetic Encoding of Phenylalanine Derivatives through Their α-Keto Acid Precursors.

The activity and function of proteins can be improved by incorporation of non-canonical amino acids (ncAAs). To avoid the tedious synthesis of a large number of chiral phenylalanine derivatives, we synthesized the corresponding phenylpyruvic acid precursors. Escherichia coli strain DH10B and strain C321.ΔA.expΔPBAD were selected as hosts for phenylpyruvic acid bioconversion and genetic code expansion using the MmPylRS/pyltRNACUA system. The concentrations of keto acids, PLP and amino donors were optimized in the process. Eight keto acids that can be biotransformed and their coupled genetic code expansions were identified. Finally, the genetic encoded ncAAs were tested for incorporation into fluorescent proteins with keto acids.

Ovarian hormones-autophagy-immunity axis in menstruation and endometriosis.

Menstruation occurs in few species and involves a cyclic process of proliferation, breakdown and regeneration under the control of ovarian hormones. Knowledge of normal endometrial physiology, as it pertains to the regulation of menstruation, is essential to understand disorders of menstruation. Accumulating evidence indicates that autophagy in the endometrium, under the regulation of ovarian hormones, can result in the infiltration of immune cells, which plays an indispensable role in the endometrium shedding, tissue repair and prevention of infections during menstruation. In addition, abnormal autophagy levels, together with resulting dysregulated immune system function, are associated with the pathogenesis and progression of endometriosis. Considering its potential value of autophagy as a target for the treatment of menstrual-related and endometrium-related disorders, we review the activity and function of autophagy during menstrual cycles. The role of the estrogen/progesterone-autophagy-immunity axis in endometriosis are also discussed.

LncRNA NEAT1 Sponges MiRNA-148a-3p to Suppress Choroidal Neovascularization and M2 macrophage polarization.

PURPOSE: Long noncoding RNAs (lncRNAs) have emerged as essential regulators in many biological processes; however, little is known about the role of lncRNAs in choroidal neovascularization (CNV). The aim of this study was to investigate the role of lncRNA NEAT1 in CNV formation, and assessed whether inhibition of lncRNA NEAT1 could suppress M2-type macrophage polarization and CNV. METHODS: The expression profiles of lncRNAs in a CNV mice model were accessed via microarray analysis. The role of lncRNA NEAT1 on macrophage polarization was assessed both in vitro and vivo. The interaction between lncRNA NEAT1, miR-148a-3p, and PTEN was assessed using a dual-luciferase reporter assay and RNA immunoprecipitation assay. Additionally, to evaluate the role of lncRNA NEAT1 on CNV development, eyes of mice in the mice CNV model were examined by Fluorescein Angiography (FA) and choroidal flatmounts on days 3 and 7 after intravitreal injection. RESULTS: The results revealed that 128 lncRNAs were significantly altered in the RPE-choroid-sclera complexes of CNV mice (P < 0.05, fold change > 2.0). Additionally, lncRNA NEAT1 increased in CNV formation and M2 macrophage polarization. LncRNA NEAT1 sponging miRNA-148a-3p targeting PTEN can modulate M2 macrophage polarization in mice CNV models as well as in bone marrow-derived macrophages cultured in vitro. Inhibition of lncRNA NEAT1 can suppress M2 macrophage both in vitro and vivo. Moreover, the intravitreal injection of a lncRNA NEAT1 Smart Silencer can inhibit CNV leakage and neovascularization. CONCLUSION: LncRNA NEAT1 via miRNA-148a-3p targeting PTEN plays a significant role in M2 macrophage polarization, while the inhibition of lncRNA NEAT1 can suppress choroidal neovascularization by inhibiting M2 macrophage polarization.

Analysis of Long Noncoding RNAs in Choroid Neovascularization.

Purpose: Choroidal neovascularization (CNV) is the major pathological features of wet age-related macular degeneration (AMD). Long noncoding RNAs play great roles in numerous biological processes. The purpose of the study was to investigate the expression profile and possible functions of the lncRNAs in CNV. Methods: In this study, the mice CNV model were conducted by laser photocoagulation. The expression profiles of lncRNAs were accessed by microarray analysis. Selected altered lncRNAs of mice CNV and wet AMD patients were validated by RT-PCR. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and lncRNA-mRNA coexpression network were conducted to reveal the biological functions. Results: The results revealed that 128 lncRNAs were significantly altered in RPE-choroid-sclera complexes of CNV mice (P < .05, fold change > 2.0). GO analysis revealed that the altered target genes of the selected lncRNAs most enriched in angiogenesis. KEGG pathway analysis demonstrated that altered target genes of lncRNAs most enriched in focal adhesion signaling pathway. H19 was significantly increased in the aqueous humor of wet AMD patients. Moreover, Inhibition of lncRNA H19 could suppresses M2 macrophage gene expression of laser-induced CNV mice. Conclusions: Our study identified differential expressions of lncRNAs in CNV, and lncRNA H19 might be novel potential target for the prevention and treatment of CNV.

Hierarchical Fabrication of DNA Wireframe Nanoarchitectures for Efficient Cancer Imaging and Targeted Therapy.

Though small-molecule drugs play a crucial role in cancer treatment, intrinsic issues such as poor solubility and systematic toxicity have considerably mitigated their anticancer functions and caused unwanted side effects. To achieve satisfying therapeutic efficiency, it is essential to develop innovative targeting systems for precise and efficient delivery of anticancer drugs. In this work, a hierarchical self-assembly strategy was applied to fabricate a core-shell nanoarchitecture composed of a DNA octahedral wireframe and chemodrug-functionalized Sgc8c aptamer. The integrated enhanced permeability and retention effect of the DNA nanostructure and active targeting ability of the Sgc8c aptamer allowed the highly selective chemodrug delivery and in vivo efficient imaging and treatment. The advantage of our multifunctional nanostructure was further highlighted by its impressive serum stability, excellent accumulation ability, deep penetration capability, significantly improved therapeutic efficacy, and favorable biosafety. This study showed promising potential of such a core-shell DNA nanoarchitecture in precise drug loading control, drug delivery, and personal medicine.

Hierarchical Self-Assembly of Cholesterol-DNA Nanorods.

Amphiphilic DNA block copolymers have been utilized in preparing self-assembled amphiphilic structures in aqueous solution. These block copolymers usually contain specifically designed hydrophobic regions, and typically assemble under near-physiological conditions. Here, we report self-assembly of spherical micelles and one-dimensional nanorods under acidic conditions from cholesterol-conjugated DNA strands (Cholesterol-DNA). Further study also revealed that the nanorods were hierarchically assembled from the micelle nanostructures. The morphology of the nanorod assemblies can be tuned by altering solution condition and the design of Cholesterol-DNA. The self-assembly of Cholesterol-DNA nanostructures under acidic conditions and the discovery of the relationship between the nanorods and the micelles can provide new insights for future design of self-assemblies of amphiphilic DNA block copolymers.