Metal-Organic Framework Supported Low-Nuclearity Cluster Catalysts for Highly Selective Carbon Dioxide Electroreduction to Ethanol.

It is still a great challenge to achieve high selectivity of ethanol in CO2 electroreduction reactions (CO2RR) because of the similar reduction potentials and lower energy barrier of possible other C2+ products. Here, we report a MOF-based supported low-nuclearity cluster catalysts (LNCCs), synthesized by electrochemical reduction of three-dimensional (3D) microporous Cu-based MOF, that achieves a single-product Faradaic efficiency (FE) of 82.5 % at -1.0 V (versus the reversible hydrogen electrode) corresponding to the effective current density is 8.66 mA cm-2. By investigating the relationship between the species of reduction products and the types of catalytic sites, it is confirmed that the multi-site synergism of Cu LNCCs can increase the C-C coupling effect, and thus achieve high FE of CO2-to-ethanol. In addition, density functional theory (DFT) calculation and operando attenuated total reflectance surface-enhanced infrared absorption spectroscopy further confirmed the reaction path and mechanism of CO2-to-EtOH.

Long-term high fructose intake promotes lacrimal gland dysfunction by inducing gut dysbiosis in mice.

The lacrimal gland is essential for maintaining ocular surface health through the secretion of the aqueous layer of the tear film. It is therefore important to explore the intrinsic and extrinsic factors that affect the structure and function of the lacrimal gland and the mechanisms underlying them. With the prevalence of Westernized diets characterized by high sugar and fat content, the susceptibility to many diseases, including ocular diseases, is increased by inducing dysbiosis of the gut microbiome. Here, we found that the composition, abundance, and diversity of the gut microbiome was significantly altered in mice by drinking 15% high fructose water for one month, as determined by 16S rRNA sequencing. This was accompanied by a significant increase in lipid deposition and inflammatory cell infiltration in the extraorbital lacrimal glands (ELGs) of mice. Transcriptome analysis based on bulk RNA-sequencing revealed abnormal activation of some of several metabolic and immune-related pathways. In addition, the secretory response to stimulation with the cholinergic receptor agonist pilocarpine was significantly reduced. However, when the composition and diversity of the gut microbiome of high fructose intake (HFI)-treated mice were improved by transplanting feces from normal young healthy mice, the pathological alterations in ELG structure, inflammatory cell infiltration, secretory function and transcriptome analysis described above were significantly reversed compared to age-matched control mice. In conclusion, our data suggest that prolonged HFI may cause pathological damage to the structure and function of the ELG through the induction of gut dysbiosis. Restoration of intestinal dysbiosis in HFI-treated mice by fecal transplantation has a potential role in ameliorating these pathological impairments.

The potential value of serum GP73 in the ancillary diagnosis and grading of liver cirrhosis.

This study is to evaluate the potential value of serum GP73 in ancillary cirrhosis diagnosis. 150 cirrhotic subjects and healthy subjects were retrospectively analyzed, and the two groups were compared in terms of Child‒Pugh grade. Serum GP73 was detected by enzyme-linked immunosorbent assay. Receiver operating characteristic curves were drawn to evaluate the diagnostic value of GP73, and the quantitative relationship between cirrhosis and GP73 was verified by logistic regression. The result showed in regard to serum biomarkers related to cirrhosis, the serum levels of GP73, TBIL, DBIL, and PT were higher and the ALB and PLT were lower in the cirrhosis group than in the control group (p = 0.000), and the area under the ROC curve of GP73 for diagnosing cirrhosis was 0.823 (p = 0.000), the cutoff value was 135 ng/ml, the sensitivity was 60.0%, and the specificity was 88.67%. Logistic regression analysis showed that GP73 > 135 ng/ml had an odds ratio of 11.735 (ß= 2.463, 95% CI: 6.432-21.411, p = 0.000) for diagnosing cirrhosis. Additionally, the Child‒Pugh A, B, and C groups had different levels of GP73 (χ2 =17.840, p = 0.000). A pairwise comparison between the groups showed that there was a significant difference between grades A and B (p = 0.004) and between grades A and C (p = 0.002), but there was no significant difference between grades B and C (p = 1.000). We found serum GP73 levels were elevated in patients with cirrhosis. When the GP73 level was >135 ng/ml, the potential risk of a cirrhosis diagnosis increased approximately 12-fold.

Anti-LINGO-1 antibody ameliorates cognitive impairment, promotes adult hippocampal neurogenesis, and increases the abundance of CB1R-rich CCK-GABAergic interneurons in AD mice.

In view of the negative regulatory effect of leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 1 (LINGO-1) on neurons, an antibody against LINGO-1 (anti-LINGO-1 antibody) was herein administered to 10-month-old APP/PS1 transgenic Alzheimer's disease (AD) mice for 2 months as an experimental intervention. Behavioral, stereology, immunohistochemistry and immunofluorescence analyses revealed that the anti-LINGO-1 antibody significantly improved the cognitive abilities, promoted adult hippocampal neurogenesis (AHN), decreased the amyloid beta (Aß) deposition, enlarged the hippocampal volume, and increased the numbers of total neurons and GABAergic interneurons, including GABAergic and CCK-GABAergic interneurons rich in cannabinoid type 1 receptor (CB1R), in the hippocampus of AD mice. In contrast, this intervention significantly reduced the number of GABAergic interneurons expressing LINGO-1 and CB1R in the hippocampus of AD mice. More importantly, we also found a negative correlation between LINGO-1 and CB1R on GABAergic interneurons in the hippocampus of AD mice, while the anti-LINGO-1 antibody reversed this relationship. These results indicated that LINGO-1 plays an important role in the process of hippocampal neuron loss in AD mice and that antagonizing LINGO-1 can effectively prevent hippocampal neuron loss and promote AHN. The improvement in cognitive abilities may be attributed to the improvement in AHN, and in the numbers of GABAergic interneurons and CCK-GABAergic interneurons rich in CB1Rs in the hippocampus of AD mice induced by the anti-LINGO-1 antibody. Collectively, the double target effect (LINGO-1 and CB1R) initiated by the anti-LINGO-1 antibody may provide an important basis for the study of drugs for the prevention and treatment of AD in the future.

NCOA5 is correlated with progression and prognosis in luminal breast cancer.

Nuclear receptor coactivator 5 (NCOA5) is known to modulate ERα-mediated transcription and has been found to be involved in the progression of several malignancies. However, the potential correlation between NCOA5 and clinical outcome in patients with luminal breast cancer remains unknown. In the present study, we demonstrated that NCOA5 was significantly up-regulated in luminal breast cancer tissues compared with adjacent non-cancerous tissues both in validated cohort and TCGA cohort. Moreover, Kaplan-Meier analysis indicated that patients with high NOCA5 expression had significantly lower overall survival (P = 0.021). Cox regression analysis indicated that the high NOCA5 expression was independent high risk factor as well as old age (>60) and HER-2 expression (P = 0.039; P = 0.003; P = 0.005; respectively). This study provides new insights and evidences that NOCA5 over-expression was significantly correlated with progression and prognosis in luminal breast cancer. However, the precise cellular mechanisms for NOCA5 in luminal breast cancer need to be further explored.

MLF1IP is correlated with progression and prognosis in luminal breast cancer.

Myeloid leukemia factor 1-interacting protein (MLF1IP) has been found to be involved in the progression of several malignancies. The potential correlation between MLF1IP and clinical outcome in patients with luminal breast cancer, however, remains unknown. In the present study, we demonstrated that MLF1IP was significantly upregulated in luminal breast cancer tissue compared with adjacent normal tissue both in validated cohort and TCGA cohort. Upregulated expression of MLF1IP was correlated with more often lymph node metastasis and negative progesterone receptor expression in TCGA cohorts. Kaplan-Meier analysis indicated that patients with high MLF1IP expression had significantly lower overall survival. Moreover, multivariate analysis revealed that high MLF1IP expression was independent high risk factor as well as old age (>60) and distant metastasis. This study provides new insights and evidences that MLF1IP over-expression plays important roles in progression of luminal breast cancer. However, the precise cellular mechanisms for MLF1IP in luminal breast cancer need to be further explored.

Primary ectopic substernal thyroid cancer with trachea relapse: a case report and opinions of management.

BACKGROUND: Ectopic substernal thyroid is a rare symptom of thyroid disease that entirely results from the developmental defects at early stages of thyroid embryogenesis and during its descent. Cases were seldom reported as primary ectopic substernal thyroid cancer, especially those with severe local invasion and tracheal relapse. CASE PRESENTATION: In this report, the patient presented odynophagia and a sense of progressing swallowing obstruction. She underwent total thyroidectomy and lump resection. However, she refused to use postoperative radioactive iodine or take adjuvant external-beam radiotherapy, except for thyroid hormone replacement therapy. Tracheal relapse was observed after 6 months. Tracheal stent was used to reconstruct the airway twice. CONCLUSIONS: Trachea invasion might be a worse independent predictor of prognosis than any others and should be given particular attention. Furthermore, tracheal stent might be a palliative option for patients with tracheal relapse.

[Spectroscopy Characterization of Anthracite Oxide].

With high degree of metamorphism and carbon content, anthracite is commonly used for activated carbon. The structural properties of anthracite play a decisive role in its materialization, while with chemical oxidation, anthracite structure can be purposefully improved. The anthracite oxide was prepared via acid leaching and oxidizing, using high carbon content and low ash content anthracite from Zhaotong, Yunnan Province, China. The structural and spectroscopy characteristics of anthracite and anthracite oxide were acquired with X-ray diffraction (XRD), Raman spectroscopy and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR). The results show that crystallites in anthracite have intermediate structures between graphite and amorphous. Compared with bitumite and lignite, its structure order degree lies between graphite and low metamorphic coals with relatively high average diameter of coal crystallites(La) and average height of coal crystallites (Lc). The process of anthracite oxidation can be modeled in two steps, the edge of crystal was curled and destroyed with strong oxidation, with the generation of CO group and intercalation of HNO3/H2SO4 into the edge layers, leading to the reducing of lateral sizes; HNO3/H2SO4 were continually intercalated into crystals, resulted in the increase of interlayer spacing (d(002)) from 0.351 to 0.361 nm, and the number of stacked layers dropped to 4.5 from 6 due to exfoliate. ID1/IG in Raman spectroscopy increased from 1.9 to 2.0, with full width at half maximum (FWHM) of G bond and intensity of D2 bond increasing from 63 to 68 and 10.26 to 13.78. Numbers of new ­C­O­, CO, ­NO2 groups generated, leading to the decrease of oxygen-containing functional groups content from 0.11 to 0.42. After HNO3/H2SO4 oxidation, the aromaticity (fa) of anthracite oxide increases, with the decrease of structure order degree and more-over a lot of active reaction sites generates in the process. The oxidation of anthracite enables anthracite has great potential in the application of porous carbon preparation.

Antagonizing LINGO-1 reduces activated microglia and alleviates dendritic spine loss in the hippocampus of APP/PS1 transgenic mice.

In Alzheimer's disease (AD), microglia are involved in synaptic pruning and mediate synapse loss. LINGO-1 is a negative regulator of nerve growth, and whether antagonizing LINGO-1 can attenuate synaptic pruning by microglia and rescue dendritic spines in the hippocampus in AD is still unclear. On this basis, the anti-LINGO-1 antibody, which binds to LINGO-1 protein and antagonizes the effects of LINGO-1, was administered to 10-month-old APP/PS1 transgenic mice for 2 months. The Morris water maze test, immunohistochemical and stereological methods, immunofluorescence and 3D reconstruction were used. Compared to wild-type mice, APP/PS1 transgenic mice had worse performance on behavioral tests, fewer dendritic spines but more microglia in the hippocampus. Meanwhile, the microglia in APP/PS1 transgenic mice had more branches of medium length (4-6 µm) and a cell body area with greater variability. Moreover, APP/PS1 transgenic mice had more postsynaptic termini colocalized with microglia in the hippocampus than wild-type mice. The anti-LINGO-1 antibody significantly reversed these changes in AD, indicating that the anti-LINGO-1 antibody can improve hippocampus-dependent learning and memory abilities and effectively rescue dendritic spines in the hippocampus of AD mice and that microglia might participate in this progression in AD. These results provide a scientific basis for further studying the mechanism of the anti-LINGO-1 antibody in AD and help to elucidate the role of LINGO-1 in the treatment of AD.

[Sample pretreatment methods of pesticide residues in Panax notoginseng of Chinese traditional medicine].

Two sample pretreatment methods of pesticide residues in Panax notoginseng of Chinese traditional medicine were developed. For Method I, the residues were extracted from homogenized tissue with n-hexane-dichloromethane (6:4) by means of ultrasonication, the crude extract was purified by an Envi-carb/NH2 solid-phase extraction (SPE) column. For Method II, matrix solid-phase dispersion (MSPD) technique was used for extracting and cleaning up. The eluates were concentrated by rotary evaporation, and then were redissolved in dichloromethane prior to GC-MS determination. The determination was performed in selected ion monitoring (SIM) mode with the external calibration for quantitative analysis. Under the optimal conditions, the results indicated that the methods are easier and faster, the recoveries of method I for the spiked standards at concentration of 0.01, 0.5, and 2.0 mg x kg(-1) were 81.90%-102.10% with the relative standard deviations (RSDs) of 3.60%-7.10%. The recoveries of method II were 96.26%-104.20% with the RSDs of 3.52%-7.94%. The detection limits (S/N) for residues of pesticides were in the range of 0.48-1.34 ng x g(-1). The results indicated that these multiresidue analysis methods can meet the requirements for determination of residue pesticides and can be appropriate for trace analysis of residue pesticides in Panax notoginseng.

Anti-LINGO-1 antibody protects neurons and synapses in the medial prefrontal cortex of APP/PS1 transgenic mice.

The medial prefrontal cortex (mPFC), one of the most vulnerable brain regions in Alzheimer's disease (AD), plays a critical role in cognition. Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein-1 (LINGO-1) negatively affects nerve growth in the central nervous system; however, its role in the pathological damage to the mPFC remains to be studied in AD. In this study, an anti-LINGO-1 antibody was administered to 10-month-old APP/PS1 mice, and behavioral tests, stereological methods, immunohistochemistry and immunofluorescence were used to answer this question. Our results revealed that LINGO-1 was highly expressed in the neurons of the mPFC of AD mice, and the anti-LINGO-1 antibody improved prefrontal cortex-related function and reduced the protein level of LINGO-1, atrophy of the volume, Aß deposition and massive losses of synapses and neurons in the mPFC of AD mice. Antagonizing LINGO-1 could effectively alleviate the pathological damage in the mPFC of AD mice, which might be an important structural basis for improving prefrontal cortex-related function. Abnormal expression of LINGO-1 in the mPFC may be one of the key targets of AD, and the effect initiated by the anti-LINGO-1 antibody may provide an important basis in the search for drugs for the prevention and treatment of AD.

Continued twitching of the latissimus dorsi miniflap after breast conservation therapy: a case report.

We report a case of continued twitching of the latissimus dorsi muscle following breast conservation therapy, along with immediate reconstruction with a latissimus dorsi miniflap, which continued despite several attempts at control including BTX-A percutaneous local injection, and was finally cured by delayed division of the thoracodorsal nerve via a small well-tolerated axillary incision.

Nano-porous Al/Au skeleton to support MnO2 with enhanced performance and electrodeposition adhesion for flexible supercapacitors.

A nano-porous Al/Au skeleton is constructed to effectively improve the utilization rate of the active MnO2 and the overall adhesion between the current collector and MnO2 in an electrodeposition system. The Al/Au current collector is prepared by first forming a nano-porous structure on the surface of Al foil through etching modification, and subsequently coating an ultra-thin Au layer onto the Al foil. The active MnO2 is electrodeposited on the Al/Au current collector to fabricate a novel Al/Au/MnO2 electrode. The nano-porous skeleton supports MnO2 to grow autonomously inside-out. The ultra-thin Au layer acts as a transition layer to improve the overall conductivity of the current collector (0.35 Ω m-1) and to improve the adhesion with MnO2 as well. Owing to the highly porous structure, the electrochemical properties of the electrode are greatly improved, as evidenced by a remarkable specific capacitance of 222.13 mF cm-2 at 0.2 mA cm-2 and excellent rate capability of 63% capacitance retention at 6.0 mA cm-2. Furthermore, the assembled solid-state symmetric supercapacitor exhibits a high energy density of 0.68 mW h cm-3, excellent cyclic stability (86.3% capacitance retention after 2000 cycles), and prominent flexibility.

The Prognostic Value of the Expression of SMC4 mRNA in Breast Cancer.

AIM: To investigate the mRNA expression and clinical significance of structural maintenance of chromosomes protein 4 (SMC4) in breast cancer. METHODS: A total of 23 paired samples were sequenced, and data from the Cancer Genome Atlas were analyzed. RESULTS: SMC4 mRNA level was significantly upregulated in breast cancer tissues (P < 0.001). Patients with high mRNA expression of SMC4 had significantly poor survival (P = 0.012). Subgroup analyses show that in nontriple negative breast cancer (non-TNBC) patients, the high SMC4 mRNA expression, older age (>65), negative progesterone receptor, and advanced stages (III-IV) were independent risk factors (HR = 3.293, 95% CI 1.257-8.625, P = 0.015). In patients with TNBC, high mRNA expression of SMC4 correlated with better survival rate (P < 0.046). CONCLUSION: SMC4 mRNA level is a good prognostic biomarker for patients with breast cancer.

Crosslinking catalytic hairpin assembly for high-contrast imaging of multiple mRNAs in living cells.

A novel DNA nanotetrad mediated crosslinking catalytic hairpin assembly (CCHA) is reported to generate clumps of cross-linked mesh products for high-contrast and simultaneous imaging of multiple mRNAs in living cells.

Coexpression of VEGF-C and COX-2 and its association with lymphangiogenesis in human breast cancer.

BACKGROUND: Lymphangiogenesis has become a new research frontier in tumor metastasis since the discovery of reliable lymphatic markers that have allowed observation and isolation of lymphatic endothelium. Cyclooxygenase-2 (COX-2) has been reported to be involved in the critical steps in carcinogenesis. However, possible role of COX-2 in lymphangiogenesis and lymphatic metastasis is still poorly understood. In present study, we aimed to investigate the relationship between vascular endothelial growth factor-C (VEGF-C) and COX-2 in human breast cancer, and correlations with lymphangiogenesis and prognosis. METHODS: Tissue samples of primary tumors from 70 patients undergoing intentionally curative surgical resections for breast cancer were immunohistochemically examined for VEGF-C, COX-2, and D2-40 expressions. The association between COX-2 and VEGF-C expressions and clinicopathological parameters as well as prognosis were analysised. To demonstrate the presence of proliferating lymphatic endothelial cells, 10 random cases with high LVD counts were selected for D2-40/Ki-67 double immunostaining. RESULTS: A significant correlation was found between the expression of VEGF-C and COX-2 (r = 0.529, P < 0.001), and both elevated VEGF-C expression and elevated COX-2 expression were associated with higher lymph vessel density (LVD), lymph node metastasis and D2-40 positive lymphatic invasion (LVI) as well as worse disease free survival (DFS) and overall survival (OS) in a univariate analysis. In the double immunostain for the lymph vessel marker D2-40 and the proliferation marker Ki-67, the results confirmed Ki-67-positive nuclei in a proportion of lymph vessel endothelial cells. CONCLUSION: There is indeed lymphangiogenesis in breast cancer, the most compelling evidence being the presence of proliferating lymphatic endothelial cells. VEGF-C and COX-2 are coexpressed and significantly associated with lymphangiogenesis and prognosis in invasive breast cancer. Suggesting COX-2 may up-regulate VEGF-C expression and thus promote lymph node metastasis via lymphangiogenesis pathway in human breast cancer.

[The effect of cyclooxygenase-2 on lymphangiogenesis in breast cancer].

OBJECTIVE: To study the effect of cyclooxygenase-2 (COX-2) on lymphangiogenesis in breast cancer. METHODS: By the means of immunohistochemistry, COX-2, vascular endothelial growth factor-C (VEGF-C) and D2-40 were examined in the tissue samples of primary tumors from 94 patients underwent surgical resections for breast cancer from November 1998 to March 2002. Eighty-three patients were followed-up. The expressions of VEGF-C mRNA and protein were detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blot in MDA-MB-231 cell lines by the treatment of selective COX-2 inhibitor Nimesulide at different doses. The expressions of VEGF-C protein were evaluated in MDA-MB-231 cells treated by PGE2 (1 microg/ml) and Trastuzumab (1 microg/ml), respectively. RESULTS: COX-2 over-expression was observed in 46.8% of surgical specimens (44/94), while VEGF-C overexpression occurred in 51.1% of tumor samples (48/94). COX-2 was strongly correlated with VEGF-C expression (P < 0.01), micro-lymphatic vessels (P = 0.032) and metastatic lymph nodes (P = 0. 035). Patients with COX-2 positive tumors had a significant shorter survival time than those with negative tumors did, including disease-free survival (P = 0.010) and overall survival (P = 0.040). Nimesulide could down-regulate the expressions of VEGF-C mRNA and protein in a does-dependent manner, while PGE2 could up-regulate the expressions. The expression of VEGF-C protein up-regulated by PGE2 treatment was decreased by Trastuzumab. CONCLUSIONS: COX-2 over-expression can up-regulate the expression of VEGF-C. VEGF-C might promote lymph node metastasis by a lymph-angiogenic pathway, then affect the prognosis of the patients with breast cancer.

Small molecule-linked programmable DNA for washing-free imaging of cell surface biomarkers.

Detection of specific biomarkers in cell membranes is critical for cell biology and disease theranostics. Here we develop a versatile terminal protection assay strategy for wash-free quantification and imaging of cell surface proteins using small molecule-linked DNA with programmable signal sequences. DNA probes are designed to link to a small molecule ligand at 3' end for specific recognition of the cell surface protein and a programmable signal sequence at 5' terminal for delivering detectable responses. Binding of the small molecule ligand to target protein enables protection of the DNA probes from exonuclease I mediated degradation, leaving the surface-binding probes intact while the non-binding probes degraded. This strategy thus allows wash-free detection of the cell surface protein via the selectively protected signal sequence. By programming the signal sequences as peroxidase-like DNAzyme, quantitative polymerase chain reaction (qPCR) targeting DNA and Ag nanoclusters (AgNCs) forming DNA template based on our new finding that the exonuclease I is able to quench the fluorescence of AgNCs, we can develop this strategy into a versatile platform for colorimetric detection, qPCR quantification and fluorescence imaging of the cell surface protein. This platform is demonstrated using a folate-linked DNA probe for folate receptor detection on tumor cell surface. The results revealed that this strategy enables highly selective and sensitive detection of the tumor cells as well as quantification and localization of the membrane protein on the cells, implying its potential in membrane protein based biomedical and clinical applications.

A novel tumor suppressor gene NCOA5 is correlated with progression in papillary thyroid carcinoma.

BACKGROUND: In contrast to the excellent prognosis for papillary thyroid carcinoma (PTC), the high incidence of lymph node metastasis (LNM) markedly increases the risk of recurrence and secondary surgery. Thus, novel biomarkers must be urgently identified to assess LNM for patients with PTC. NCOA5 is deeply involved in the progression of human cancer; however, its role in thyroid cancer remains unknown. PATIENTS AND METHODS: Quantitative real-time polymerase chain reaction was conducted to investigate the expression of NCOA5 in PTC. RNA-seq data from The Cancer Genome Atlas (TCGA) database were downloaded to further understand the role of NCOA5 in PTC and its relationship with LNM. RESULTS: NCOA5 was significantly downregulated in PTC tissues when compared with that in adjacent noncancerous thyroid tissues both in our local cohort and TCGA database. Reduced expression of NCOA5 was significantly associated with aggressive clinicopathological features, including histological type, tumor stage, BRAF-V600E mutation, LNM, extrathyroid extension, and clinical stage. Moreover, logistic analysis indicated that reduced expression of NCOA5, age, histological type, and clinical stage are independent high-risk factors for LNM in PTC. CONCLUSION: Our study provides new insights and evidence that NOCA5 was significantly correlated with the progression of PTC and was particularly involved in LNM.

Protein scaffolded DNA tetrads enable efficient delivery and ultrasensitive imaging of miRNA through crosslinking hybridization chain reaction.

Efficient intracellular delivery of nucleic acids to achieve sensitive detection and gene regulation is essential for chemistry and biology. Here we developed a novel protein scaffolded DNA tetrad, a four-arm DNA nanostructure constructed using streptavidin (SA) protein and four biotinylated hairpin DNA probes for efficient nucleic acid delivery and ultrasensitive miRNA imaging through crosslinking hybridization chain reaction (cHCR). DNA tetrads were easy to prepare and allowed precise control of the structure of the probes. DNA tetrads showed rapid intracellular delivery of DNA probes and high efficiency in lysosome escape by using confocal images for individual cells and flow cytometry for a large population of cells. cHCR allowed generating clumps of crosslinked hydrogel networks specifically to target miRNA, affording high sensitivity and spatial resolution for imaging. To our knowledge, this is the first time that HCR amplification has been realized in situ on nanostructures. Moreover, the FRET based design of cHCR conferred improved precision with the use of dual-emission ratiometric imaging to avoid false signals in biological systems. Intracellular imaging experiments further showed that DNA tetrad based cHCR could realize ultrasensitive and accurate miRNA imaging in living cells. Moreover, DNA tetrad based cHCR provided a potential tool for quantitative measurement of intracellular miRNA. The results suggested that this developed strategy provided a useful platform for nucleic acid delivery and low level biomarker imaging.