Fluid-Dynamics-Rectified Chemical Vapor Deposition (CVD) Preparing Graphene-Skinned Glass Fiber Fabric and Its Application in Natural Energy Harvest.

Graphene chemical vapor deposition (CVD) growth directly on target using substrates presents a significant route toward graphene applications. However, the substrates are usually catalytic-inert and special-shaped; thus, large-scale, high-uniformity, and high-quality graphene growth is challenging. Herein, graphene-skinned glass fiber fabric (GGFF) was developed through graphene CVD growth on glass fiber fabric, a Widely used engineering material. A fluid dynamics rectification strategy was first proposed to synergistically regulate the distribution of carbon species in 3D space and their collisions with hierarchical-structured substrates, through which highly uniform deposition of high-quality graphene on fibers in large-scale 3D-woven fabric was realized. This strategy is universal and applicable to CVD systems using various carbon precursors. GGFF exhibits high electrical conductivity and photothermal conversion capability, based on which a natural energy harvester was first developed. It can harvest both solar and raindrop energy through solar heating and droplet-based electricity generating, presenting promising potentials to alleviate energy burdens.

Diosgenin improves post-myocardial infarction cardiac function via HAND2-induced angiogenesis.

While diosgenin has been demonstrated effective in various cardiovascular diseases, its specific impact on treating heart attacks remains unclear. Our research revealed that diosgenin significantly improved cardiac function in a myocardial infarction (MI) mouse model, reducing cardiac fibrosis and cell apoptosis while promoting angiogenesis. Mechanistically, diosgenin upregulated the Hand2 expression, promoting the proliferation and migration of endothelial cells under hypoxic conditions. Acting as a transcription factor, HAND2 activated the angiogenesis-related gene Aggf1. Conversely, silencing Hand2 inhibited the diosgenin-induced migration of hypoxic endothelial cells and angiogenesis. In summary, these findings provide new insights into the protective role of diosgenin in MI, validating its effect on angiogenic activity and providing a theoretical basis for clinical treatment strategies.

Diagnosis and management of urinary bladder paragangliomas: A Sino-American-European retrospective observational study.

OBJECTIVE: Paragangliomas of the urinary bladder (UBPGLs) are rare neuroendocrine tumours and pose a diagnostic and surgical challenge. It remains unclear what factors contribute to a timely presurgical diagnosis. The purpose of this study is to identify factors contributing to missing the diagnosis of UBPGLs before surgery. DESIGN, PATIENTS AND MEASUREMENTS: A total of 73 patients from 11 centres in China, and 51 patients from 6 centres in Europe and 1 center in the United States were included. Clinical, surgical and genetic data were collected and compared in patients diagnosed before versus after surgery. Logistic regression analysis was used to identify clinical factors associated with initiation of presurgical biochemical testing. RESULTS: Among all patients, only 47.6% were diagnosed before surgery. These patients were younger (34.0 vs. 54.0 years, p < .001), had larger tumours (2.9 vs. 1.8 cm, p < .001), and more had a SDHB pathogenic variant (54.7% vs. 11.9%, p < .001) than those diagnosed after surgery. Patients with presurgical diagnosis presented with more micturition spells (39.7% vs. 15.9%, p = .003), hypertension (50.0% vs. 31.7%, p = .041) and catecholamine-related symptoms (37.9% vs. 17.5%, p = .012). Multivariable logistic analysis revealed that presence of younger age (<35 years, odds ratio [OR] = 6.47, p = .013), micturition spells (OR = 6.79, p = .007), hypertension (OR = 3.98, p = .011), and sweating (OR = 41.72, p = .013) increased the probability of initiating presurgical biochemical testing. CONCLUSIONS: Most patients with UBPGL are diagnosed after surgery. Young age, hypertension, micturition spells and sweating are clues in assisting to initiate early biochemical testing and thus may establish a timely presurgical diagnosis.

N6-methyladenosine modification of OIP5-AS1 promotes glycolysis, tumorigenesis, and metastasis of gastric cancer by inhibiting Trim21-mediated hnRNPA1 ubiquitination and degradation.

BACKGROUND: Opa-interacting protein 5 antisense transcript 1 (OIP5-AS1) has been demonstrated to play vital roles in development and progression of tumors such as gastric cancer (GC). However, the detailed molecular mechanism of OIP5-AS1 has not been completely elucidated. Our study aimed to investigate the role and the epigenetic regulation mechanism of OIP5-AS1 in GC. METHODS: OIP5-AS1 expression in GC tissues was detected by RT-qPCR. Loss- and gain-of-function experiments were conducted to assess the biological function of OIP5-AS1 in vitro and in vivo. The interaction of OIP5-AS1 with insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) or heterogeneous nuclear nucleoprotein A1 (hnRNPA1) was verified by bioinformatics analysis, RNA pull-down assays, and RNA immunoprecipitation assays. RESULTS: In this study, we identified that OIP5-AS1 is specifically overexpressed in GC tumor tissues and cell lines and correlated with a poor prognosis. The loss of OIP5-AS1 suppressed the proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and glycolysis of GC cells, but the ectopic expression of OIP5-AS1 had the opposite impact. Meanwhile, knockdown of OIP5-AS1 inhibited tumor growth in patient-derived xenograft models, as well as repressed tumor metastasis. Mechanistically, IGF2BP3 could bind to OIP5-AS1 by N6-methyladenosine (m6A) modification sites on OIP5-AS1, thereby stabilizing OIP5-AS1. Moreover, OIP5-AS1 prevented Trim21-mediated ubiquitination and degradation of hnRNPA1, stabilizing hnRNPA1 protein and promoting the malignant progression of GC by regulating PKM2 signaling pathway. CONCLUSIONS: In conclusion, this study highlighted that OIP5-AS1 is an oncogenic m6A-modified long non-coding RNA (lncRNA) in GC and that IGF2BP3/OIP5-AS1/hnRNPA1 axis may provide a potential diagnostic or prognostic target for GC.

A transcriptomic analysis of dental pulp stem cell senescence in vitro.

BACKGROUND/PURPOSE: The use of human dental pulp stem cells (hDPSCs) as autologous stem cells for tissue repair and regenerative techniques is a significant area of global research. The objective of this study was to investigate the effects of long-term in vitro culture on the multidifferentiation potential of hDPSCs and the potential molecular mechanisms involved. MATERIALS AND METHODS: The tissue block method was used to extract hDPSCs from orthodontic-minus-extraction patients, which were then expanded and cultured in vitro for 12 generations. Stem cells from passages three, six, nine, and twelve were selected. Flow cytometry was used to detect the expression of stem cell surface markers, and CCK-8 was used to assess cell proliferation. ß-Galactosidase staining was employed to detect cellular senescence, Alizarin Red S staining to assess osteogenic potential, and Oil Red O staining to evaluate lipogenic capacity. RNA sequencing (RNA-seq) was conducted to identify differentially expressed genes in DPSCs and investigate their potential mechanisms. RESULTS: With increasing passage numbers, pulp stem cells showed an increase in senescence and a decrease in proliferative capacity and osteogenic-lipogenic multidifferentiation potential. The expression of stem cell surface markers CD34 and CD45 was stable, whereas the expression of CD73, CD90, and CD105 decreased with increasing passages. According to the RNA-seq analysis, the differentially expressed genes CFH, WNT16, HSD17B2, IDI1, and COL5A3 may be associated with stem cell senescence. CONCLUSION: Increased in vitro expansion induced cellular senescence in pulp stem cells, which resulted in a reduction in their proliferative capacity and osteogenic-lipogenic differentiation potential. The differential expression of genes such as CFH, WNT16, HSD17B2, IDI1, and COL5A3 may represent a potential mechanism for the induction of cellular senescence in pulp stem cells.

Analysis of functional connectivity changes in attention networks and default mode networks in patients with depression and insomnia.

PURPOSE: Major Depressive Disorder (MDD) and Insomnia Disorder (ID) are prevalent psychiatric conditions often occurring concurrently, leading to substantial impairment in daily functioning. Understanding the neurobiological underpinnings of these disorders and their comorbidity is crucial for developing effective interventions. This study aims to analyze changes in functional connectivity within attention networks and default mode networks in patients with depression and insomnia. METHODS: The functional connectivity alterations in individuals with MDD, ID, comorbid MDD and insomnia (iMDD), and healthy controls (HC) were assessed from a cohort of 174 participants. They underwent rs-fMRI scans, demographic assessments, and scale evaluations for depression and sleep quality. Functional connectivity analysis was conducted using region-of-interest (ROI) and whole-brain methods. RESULTS: The MDD and iMDD groups exhibited higher Hamilton Depression Scale (HAMD) scores compared to HC and ID groups (P < 0.001). Both ID and MDD groups displayed enhanced connectivity between the left and right orbital frontal cortex compared to HC (P < 0.05), while the iMDD group showed reduced connectivity compared to HC and ID groups (P < 0.05). In the left insula, reduced connectivity with the right medial superior frontal gyrus was observed across patient groups compared to HC (P < 0.05), with the iMDD group showing increased connectivity compared to MDD (P < 0.05). Moreover, alterations in functional connectivity between the left thalamus and left temporal pole were found in iMDD compared to HC and MDD (P < 0.05). Correlation analyses revealed associations between abnormal connectivity and symptom severity in MDD and ID groups. CONCLUSIONS: Our findings demonstrate distinct patterns of altered functional connectivity in individuals with MDD, ID, and iMDD compared to healthy controls. These findings contribute to a better understanding of the pathophysiology of depression and insomnia, which could be used as a reference for the diagnosis and treatments of these patients.

Photocatalytic Multisite Functionalization of Unactivated Terminal Alkenes by Merging Polar Cycloaddition and Radical Ring-Opening Process.

Although highly appealing for rapid access of molecular complexity, multi-functionalization of alkenes that allows incorporation of more than two functional groups remains a prominent challenge. Herein, we report a novel strategy that merges dipolar cycloaddition with photoredox promoted radical ring-opening remote C(sp3)-H functionalization, thus enabling a smooth 1,2,5-trifunctionalization of unactivated alkenes. A highly regioselective [3+2] cycloaddition anchors a reaction trigger onto alkene substrates. The subsequent halogen atom transfer (XAT) selectively initiates ring-opening process, which is followed by a series of 1,5-hydrogen atom transfer (1,5-HAT) and intermolecular fluorine atom transfer (FAT) events. With this method, site-selective introduction of three different functional groups is accomplished and a broad spectrum of valuable ß-hydroxyl-ϵ-fluoro-nitrile products are synthesized from readily available terminal alkenes.

Functionalized DNA-Origami-Protein Nanopores Generate Large Transmembrane Channels with Programmable Size-Selectivity.

The DNA-origami technique has enabled the engineering of transmembrane nanopores with programmable size and functionality, showing promise in building biosensors and synthetic cells. However, it remains challenging to build large (>10 nm), functionalizable nanopores that spontaneously perforate lipid membranes. Here, we take advantage of pneumolysin (PLY), a bacterial toxin that potently forms wide ring-like channels on cell membranes, to construct hybrid DNA-protein nanopores. This PLY-DNA-origami complex, in which a DNA-origami ring corrals up to 48 copies of PLY, targets the cholesterol-rich membranes of liposomes and red blood cells, readily forming uniformly sized pores with an average inner diameter of ∼22 nm. Such hybrid nanopores facilitate the exchange of macromolecules between perforated liposomes and their environment, with the exchange rate negatively correlating with the macromolecule size (diameters of gyration: 8-22 nm). Additionally, the DNA ring can be decorated with intrinsically disordered nucleoporins to further restrict the diffusion of traversing molecules, highlighting the programmability of the hybrid nanopores. PLY-DNA pores provide an enabling biophysical tool for studying the cross-membrane translocation of ultralarge molecules and open new opportunities for analytical chemistry, synthetic biology, and nanomedicine.

PD-L1 Expression is Linked to Tumor-Infiltrating T-Cell Exhaustion and Adverse Pathological Behavior in Pheochromocytoma/Paraganglioma.

Pheochromocytoma/paraganglioma (PPGL) is an endocrine-related tumor associated with excessive catecholamine release and has limited treatment options once metastasis occurs. Although recent phase 2 clinical trials of immune checkpoint inhibitors in the treatment of PPGL have preliminarily shown promising results, the fundamentals of immunotherapy for PPGL have not yet been established. In the early research, using bulk RNA sequencing of tumor samples from 7 PPGL patients, we found that PPGL tumor tissues exhibited high PD-L1 mRNA expression compared with adjacent normal adrenal medulla tissues, and this was related to T-cell exhaustion biomarkers. To further validate the association, in this study (n = 60), we first stratified all PPGL samples according to PD-L1 expression as determined by immunohistochemical staining, and then subjected 23 fresh PPGL tumor samples from the cohort to a quantitative polymerase chain reaction (n = 16), flow cytometry (n = 7), and multiplex-immunofluorescence staining. Subsequently, we evaluated the pathological manifestations of all 60 PPGL tumor samples and analyzed the correlation among PD-L1 expression, adverse pathological behavior, various clinicopathological data, and genotypes in PPGL. The results showed that PD-L1-positive expression correlated with the exhaustion of tumor-infiltrating T cells, preoperative abnormal elevation of plasma norepinephrine, high Ki67 index, and adverse pathological behavior in PPGL but not with genetic mutation or metastatic disease, possibly due to the limitation of the small number of patients with metastatic disease (n = 4) in the study cohort. In conclusion, our findings reveal that PD-L1 expression is associated with T-cell exhaustion and adverse pathological behavior in PPGL. These results are expected to provide a new theoretical basis and clinical guidance for the treatment of PPGL.

Copper Activation Enabling Reversible Aqueous Cu-ZnS Battery Chemistry.

The aqueous metal-sulfide batteries (AMSBs) have attracted research interest due to their high capacity, environmentally friendly qualities, and the accessibility of raw materials. However, the design strategies for metal-sulfide cathode have rarely been reported. Here, the copper-activated sphalerite in which Zn2+ is substituted by Cu2+ through ion exchange has been introduced for the first time as cathode for aqueous Cu/ZnS batteries. After sphalerite transformed to CuS, a two-step conversion of CuS→Cu7 S4 →Cu2 S storage mechanism has been proposed. At 0.7 A g-1 current density, the capacity can reach 532.4 mAh g-1 after 100 cycles. When cycled once at a current density of 35 mA g-1 , the initial reversible capacity can reach 461 mAh g-1 under 1 A g-1 . Furthermore, the assembled Zn//ZnS hybrid ion cell delivers an energy of up to 460 Wh kg-1 , which is better than for many AMSBs.

Molecular Lithography on Silicon Wafers Guided by Porous, Extended Arrays of Small DNA Tiles.

Tile-based DNA self-assembly is a cost-effective fabrication method for large-scale nanopatterns. Herein, we report a protocol to directly assemble DNA 2D arrays on silicon wafers and then use the DNA nanostructures as molds to fabricate the corresponding nanostructures on the silicon wafers by hydrogen fluoride (HF) etching. Similar HF etching has been used with robust large DNA origami structures as templates. This work demonstrates that DNA nanostructures assembled from small tiles are sufficiently stable for this process. The resulting feature size (∼8.6 nm) approaches the sizes of e-beam lithography. While the reported method is parallel and inexpensive, e-beam lithography is a serial method and is expensive. We expect that this method will be very useful for preparing fine nanopatterns in large areas.

Impact of combining Lenvatinib with Transarterial chemoembolization for unresectable hepatocellular carcinoma.

Objectives: To investigate the impact of combining lenvatinib with transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (HCC). Methods: This was a retrospective observational study which reviewed the medical records of 103 unresectable HCC patients from January 2017 to June 2020 in The First Affiliated Hospital of Soochow University. It included 46 patients who received TACE plus lenvatinib and 57 patients who received TACE alone. The levels of serum indicators, clinical effect, adverse events, overall survival (OS), and progression-free survival (PFS) were compared between the two groups. Results: AFP and VEGF levels in the TACE+lenvatinib group post-treatment were significantly lower than the TACE group (P<0.05). The clinical efficacy in the TACE+lenvatinib group (69.57%) was higher than that in the TACE group (40.35%) post-treatment (P<0.05). There were significant differences in hypertension, diarrhea, and bleeding (gingiva) between the two groups (P<0.05). There were no significant differences in one or two year PFS rate or one year OS between groups (P>0.05), while the two years survival rate in the TACE+lenvatinib group was significantly higher than that in the TACE group (P<0.05). Conclusions: TACE combined with lenvatinib have a high clinical effective rate, with reduced AFP and VEGF levels, higher two year survival rate, and acceptable incidence of adverse events.

Sublytic C5b-9 triggers glomerular mesangial cell proliferation via enhancing FGF1 and PDGFα gene transcription mediated by GCN5-dependent SOX9 acetylation in rat Thy-1 nephritis.

Rat Thy-1 nephritis (Thy-1N) is an animal model of human mesangioproliferative glomerulonephritis (MsPGN), accompanied by glomerular mesangial cell (GMC) proliferation and extracellular matrix (ECM) deposition. Although sublytic C5b-9 formed on GMC membrane could induce cell proliferation, the mechanism is still unclear. In this study, we first demonstrated that the level of SRY related HMG-BOX gene 9 (SOX9), general control nonderepressible 5 (GCN5), fibroblast growth factor 1 (FGF1) and platelet-derived growth factor α (PDGFα) was all elevated both in the renal tissues of Thy-1N rats (in vivo) and in the GMCs (in vitro) with sublytic C5b-9 stimulation. Then, we not only discovered that sublytic C5b-9 caused GMC proliferation through increasing SOX9, GCN5, FGF1 and PDGFα expression, but also proved that SOX9 and GCN5 formed a complex and combined with FGF1 and PDGFα promoters, leading to FGF1 and PDGFα gene transcription. More importantly, GCN5 could mediate SOX9 acetylation at lysine 62 (K62) to enhance SOX9 binding to FGF1 or PDGFα promoter and promote FGF1 or PDGFα synthesis and GMC proliferation. Besides, the experiments in vivo also showed that FGF1 and PDGFα expression, GMC proliferation and urinary protein secretion in Thy-1N rats were greatly reduced by silencing renal SOX9, GCN5, FGF1 or PDGFα gene. Furthermore, the renal tissues of MsPGN patients also exhibited positive expression of these genes mentioned above. Collectively, our findings indicate that GCN5, SOX9 and FGF1/PDGFα can form an axis and play an essential role in sublytic C5b-9-triggered GMC proliferation, which might provide a novel insight into the pathogenesis of Thy-1N and MsPGN.

Differences in clinical presentation and management between pre- and postsurgical diagnoses of urinary bladder paraganglioma: is there clinical relevance? A systematic review.

PURPOSE: Paraganglioma of the urinary bladder (UBPGL) is a rare neuroendocrine tumor diagnosed in many patients only after surgery. We, therefore, assessed clinical clues relevant to presurgical diagnosis and clinical consequences in patients with a missed presurgical diagnosis of UBPGL. MATERIALS AND METHODS: Case reports describing a UBPGL (published from 1-1-2001 and 31-12-2020) were identified in Pubmed. Two authors independently performed data extraction and assessed data quality according to the PRISMA guideline. Patients were divided into two groups: UBPGL diagnosis before and after surgery. RESULTS: We included 177 articles reporting 194 cases. In 90 (46.4%) patients, the UBPGL was diagnosed before and in 104 (53.6%) after surgery. In presurgically diagnosed UBPGL, hypertension and catecholamine-associated symptoms were 2- to 3-fold (p < 0.001) more frequent than in postsurgically diagnosed patients whereas hematuria was twofold (p = 0.003) more prevalent in those with postsurgical diagnosis. Hypertension was an independent factor for presurgical biochemical testing (OR 4.45, 95% CI 1.66-11.94) while hematuria (OR 0.23, 95% CI 0.09-0.60) was an independent factor for not performing presurgical biochemical testing. Most patients diagnosed after surgery were not pretreated with alpha-adrenoceptor blockade (95.2%), underwent more frequently transurethral resection instead of cystectomy (70.2% vs. 23.1%) and had more frequent peroperative complications and residual tumor mass. CONCLUSIONS: In nearly half of all patients with a UBPGL, the diagnosis was not established before surgery. Hypertension and hematuria contributed independently to a presurgical diagnosis. Postsurgical diagnosis, which was associated with suboptimal presurgical and surgical management, resulted in more peroperative complications and incomplete tumor resections.

CT imaging findings of renal epithelioid lipid-poor angiomyolipoma.

OBJECTIVES: To identify specific imaging and clinicopathological features of a rare potentially malignant epithelioid variant of renal lipid-poor angiomyolipoma (E-lpAML). METHODS: A total of 20 patients with E-lpAML and 43 patients with other lpAML were retrospectively included. Multiphase computed tomography (CT) imaging features and clinicopathological findings were recorded. Independent predictors for E-lpAML were identified using multivariate logistic regression and were used to construct a diagnostic score for differentiation of E-lpAML from other lpAML. RESULTS: The E-lpAML group consisted of 6 men and 14 women (age median ± SD: 39.45 ± 15.70, range: 16.0-68.0 years). E-lpAML tended to appear as hyperdense mass lesions located at the renal sinus (n = 8, 40%) or at the renal cortex (n = 12, 60%), with a "fast-in and slow-out" enhancement pattern (n = 20, 100%), cystic degeneration (n = 18, 90%), "eyeball" sign (n = 11, 55%), and tumor neo-vasculature (n = 15, 75%) on CT. Multivariate logistic regression analysis showed that the independent predictors for diagnosing E-lpAML were cystic degeneration on CT imaging and CT value of the tumor in corticomedullary phase of enhancement. A predictive model was built with the two predictors, achieving an area under the curve (AUC) of 93.5% (95% confidence interval (95%CI): 84.3-98.2%) with a sensitivity of 95.0% (95%CI: 75.1-99.9%) and a specificity of 83.72% (95%CI: 69.3-93.2%). CONCLUSION: We identified specific CT imaging features and predictors that could contribute to the correct diagnosis of E-lpAML. Our findings should be helpful for clinical management of E-lpAML which could potentially be malignant and may require nephron-sparing surgery while other lpAML tumors which are benign require no intervention. KEY POINTS: • It is important to differentiate renal epithelioid lipid-poor angiomyolipoma (E-lpAML) from other lpAML because of differences in clinical management. • E-lpAML tumors tend to be large hyperdense tumors in the renal sinus with cystic degeneration and "fast-in and slow-out" pattern of enhancement. • Our CT imaging-based predictive model was robust in its performance for predicting E-lpAML from other lpAML tumors.

Long non-coding RNA FEZF1-AS1 promotes rectal cancer progression by competitively binding miR-632 with FAM83A.

The long non-coding RNA (lncRNA) forebrain embryonic zinc finger protein 1 antisense RNA1 (FEZF1-AS1) was recently identified as an oncogenic gene in several types of tumors. The biological function of FEZF1-AS1 in rectal cancer progression, however, remains unknown. In the present study, we discover that FEZF1-AS1 is significantly upregulated in rectal cancer tissues and cells. Knocking down of FEZF1-AS1 suppresses cell proliferation, migration, and invasion , and tumorigenesis . Furthermore, FEZF1-AS1 functions as a competing endogenous RNA (ceRNA) for miR-632, resulting in the suppression of family with sequence similarity 83, member A (FAM83A). Overall, our findings reveal that FEZF1-AS1/miR-632/FAM83A axis plays an oncogenic role in rectal cancer progression, suggesting that it may be a novel therapeutic target for rectal cancer.

5'-Phosphorylation Strengthens Sticky-End Cohesions.

Sticky-end cohesion plays a critical role in molecular biology and nucleic acid nanotechnology. Although free energy calculations and molecular mechanics can predict these interactions, chemical modification would compromise such predictions. Herein, we have used rationally designed 3D DNA crystals as a tool to experimentally investigate the modulation of 5'-phosphorylation on sticky-end cohesions. We have found that 5'-phosphorylation strengthens the sticky-end cohesion: in a DNA crystal self-assembled exclusively via sticky-end cohesions, 5'-phosphorylation not only promotes the crystallization process, in general, but also accelerates the crystal growth along designed directions. Such a finding allows the fine-tuning of DNA crystallization kinetics and the control of DNA crystal morphology. It also suggests a potential difference in self-assembly kinetics between natural DNA (with 5'-phosphorylation) and synthetic DNA (without 5'-phosphorylation).

Kinetic DNA Self-Assembly: Simultaneously Co-folding Complementary DNA Strands into Identical Nanostructures.

DNA origami is a powerful method for constructing DNA nanostructures. It requires long single-stranded DNAs. The preparation of such long DNA strands is often quite tedious and has a limited production yield. In contrast, duplex DNAs can be easily prepared via enzymatic reactions in large quantities. Thus, we ask a question: can we design DNA nanostructures in such a way that the two complementary strands can simultaneously fold into the designed structures in the same solution instead of hybridizing with each other to form a DNA duplex? By engineering DNA interaction kinetics, herein we are able to provide multiple examples to concretely demonstrate a positive answer to this question. The resulting DNA nanostructures have been thoroughly characterized by electrophoresis and atomic force microscopy imaging. The reported strategy is compatible with the DNA cloning method and thus would provide a convenient method for the large-scale production of the designed DNA nanostructures.

A poly(thymine)-melamine duplex for the assembly of DNA nanomaterials.

The diversity of DNA duplex structures is limited by a binary pair of hydrogen-bonded motifs. Here we show that poly(thymine) self-associates into antiparallel, right-handed duplexes in the presence of melamine, a small molecule that presents a triplicate set of the hydrogen-bonding face of adenine. X-ray crystallography shows that in the complex two poly(thymine) strands wrap around a helical column of melamine, which hydrogen bonds to thymine residues on two of its three faces. The mechanical strength of the thymine-melamine-thymine triplet surpasses that of adenine-thymine base pairs, which enables a sensitive detection of melamine at 3 pM. The poly(thymine)-melamine duplex is orthogonal to native DNA base pairing and can undergo strand displacement without the need for overhangs. Its incorporation into two-dimensional grids and hybrid DNA-small-molecule polymers highlights the poly(thymine)-melamine duplex as an additional tool for DNA nanotechnology.

Self-assembled RNA nanocarrier-mediated chemotherapy combined with molecular targeting in the treatment of esophageal squamous cell carcinoma.

BACKGROUND: Esophageal cancer is the fifth most common cancer affecting men in China. The primary treatment options are surgery and traditional radio-chemotherapy; no effective targeted therapy exists yet. Self-assembled RNA nanocarriers are highly stable, easily functionally modified, and have weak off-tumor targeting effects. Thus, they are among the most preferred carriers for mediating the targeted delivery of anti-tumor drugs. miR-375 was found to be significantly down-regulated in esophageal squamous cell carcinoma (ESCC) tissues and its overexpression effectively inhibits the proliferation, migration, and invasion of ESCC cells. Moreover, epidermal growth factor receptor (EGFR) was overexpressed in ESCC cells, and accumulation of RNA nanoparticles in ESCC tumors was enhanced by EGFR-specific aptamer (EGFRapt) modification. RESULTS: Herein, a novel four-way junction RNA nanocarrier, 4WJ-EGFRapt-miR-375-PTX simultaneously loaded with miR-375, PTX and decorated with EGFRapt, was developed. In vitro analysis demonstrated that 4WJ-EGFRapt-miR-375-PTX possesses strong thermal and pH stabilities. EGFRapt decoration facilitated tumor cell endocytosis and promoted deep penetration into 3D-ESCC spheroids. Xenograft mouse model for ESCC confirmed that 4WJ-EGFRapt-miR-375-PTX was selectively distributed in tumor sites via EGFRapt-mediating active targeting and targeted co-delivery of miR-375 and PTX exhibited more effective therapeutic efficacy with low systemic toxicity. CONCLUSION: This strategy may provide a practical approach for targeted therapy of ESCC.