Endothelial lipase promotes acute myeloid leukemia progression through metabolic reprogramming.

Metabolic reprogramming occurs in the clonal evolution of acute myeloid leukemia (AML), which contributes to cell survival under metabolic stress and the development of drug resistance. Leukemic cells exhibit various metabolic profiles, which involve multiple metabolic pathways due to the heterogeneity of AML. However, studies on metabolic targets for AML treatment are mostly focused on glycolysis at present. In this work, we established conditional knock-in AML mouse models harboring Dnmt3aR878H/WT, NrasG12D/WT, and both of the mutations, respectively. Transcriptomic analysis of Gr1+ cells from bone marrow was performed afterward to screen interested metabolic pathways and target genes. Candidate genes were studied using the CRISPR/Cas9 technique, quantitative real-time RT-PCR, and flow cytometric analyses. We revealed that multiple metabolic pathways were affected in AML mice, including lipid metabolism. Endothelial lipase (LIPG) was obviously upregulated in leukemic cells from AML mice with Dnmt3a mutation. We performed knockout of LIPG in OCI-AML3 cells carrying DNMT3A R882C mutation by using the CRISPR/Cas9 technique. Depletion of LIPG led to proliferation inhibition, apoptosis, damage of antioxidant capacity, and myeloid differentiation in OCI-AML3 cells. LIPG might serve as a potential metabolic target for the treatment of AML with abnormal lipid metabolism.

Could the EQ-5D-3L predict all-cause mortality in older Chinese? Evidence from a 5-year longitudinal study in eastern China.

PURPOSE: To assess the ability of the 3-level EQ-5D (i.e., EQ-5D-3L) in predicting all-cause mortality in older Chinese adults. METHODS: The data were from a 5-year longitudinal study, Weitang Geriatric Diseases Study, including 4579 community-dwelling older people in eastern China, with the mean age of 72.5 years at baseline and female being 52.0%. Three multivariable logistic regression models were adopted to assess the associations of the baseline EQ-5D data [i.e., the EQ-5D problems, EQ-5D-3L index score, and EQ-5D visual analog scale (VAS) score] with the 5-year all-cause mortality, adjusting for socio-demographic characteristics, and subsequently, health conditions and lifestyle habits. RESULTS: A total of 183 participants died over the 5-year study period. A larger proportion of the dead reported problems in physical dimensions (i.e., including three dimensions: mobility, self-care, and usual activities, p < 0.05 for all). The mean EQ-5D index score (0.928) and EQ-VAS score (79.7) of the living were higher than those of the dead (0.915 and 73.2, p < 0.05 for both). In multivariable logistic analyses, the EQ-5D health problems in the physical-related dimensions [odds ratio (OR) 2.16, p < 0.05] and the EQ-VAS score (OR: 0.97, p < 0.001) were associated with the 5-year all-cause mortality when adjusting for socio-demographic characteristics, health conditions, and lifestyle habits. CONCLUSIONS: It appears that the EQ-5D-3L could predict mortality in general older Chinese, which could be used to detect high-risk older individuals in China.

Tea consumption and serum uric acid levels among older adults in three large-scale population-based studies in China.

BACKGROUND AND AIMS: The association between serum uric acid (SUA) and tea consumption has been studied in previous work, and there were arguments among various population group employed as well as different statistical approaches. The aim of this work is to investigate the tea effect on SUA levels among older adults by comparing three large-scale populations with both cross-sectional and longitudinal analyses. METHOD: We examined the relationship between intake and SUA levels among older adults using linear regression. All the studies include the parameters SUA levels, tea intake, age, sex, education level, smoking status, alcohol drinking status, body mass index (BMI), and health history (diabetes, hypertension, and fasting plasma glucose). The cross-sectional analyses were conducted with 4579 older adults in the Weitang Geriatric Diseases Study (WGDS, ≥60 years), 2440 in the China Health and Nutrition Survey (CHNS, ≥60 years) and 1236 in the Chinese Longitudinal Healthy Longevity Survey (CLHLS, ≥62 years); and the longitudinal analyses were performed with 3870 (84.5%) in the WGDS and 420 (34.0%) in the CLHLS. Multivariable linear regression analyses were performed in both cross-sectional and longitudinal studies. RESULTS: Cross-sectional studies showed that tea consumers tended to have higher SUA levels than non-tea consumers in all the three datasets (P < 0.05). However, longitudinal associations of SUA levels with tea consumption had no statistical significance (P>0.05). The results of sex-stratified analyses were consistent with those of the whole datasets. CONCLUSIONS: This work implied that any possible association between tea consumption and SUA levels could be very weak.

In Situ Visualization of hERG Potassium Channel via Dual Signal Amplification.

Dysfunction of the human ether-a-go-go related gene (hERG)-encoded potassium channel is identified as a major cause of the long QT syndrome, a marker for lethal cardiac arrhythmia. Furthermore, recent studies revealed that hERG K+ channel is a regulator of tumor cell apoptosis and proliferation. Herein, an ultrasensitive fluorescence assay combining DNA-functionalized gold nanoparticles and rolling circle amplification (RCA) was attempted for the first time to visualize hERG channels in living cells. The spherical nucleic acid gold nanoparticles, which can anchor on hERG channels in the cell membrane, not only act as the primary amplification elements but also trigger the subsequent RCA reaction to achieve the secondary amplification. Within 30 min, the ratio of reporter to target can reach up to 104, realizing the detection of hERG channels in cells with low-level expression. Therefore, the strategy provides a valuable tool for hERG-related studies. More importantly, it opens a new horizon for imaging various membrane proteins which possess specific aptamers or antibodies.

RNA chaperone assisted intramolecular annealing reaction towards oligouridylated RNA detection in cancer cells.

Proximity induced intramolecular nucleotide strand displacement, which can be simply performed in a single tube or in a complex cellular environment, is one of the key mechanisms for the detection of biological targets, especially for significant genetic molecules. The host factor for RNA phage Qb replication (Hfq), with two distinct single stranded RNA binding sites, has excellent properties as an affinity ligand in a proximity induced reaction. In this research, a versatile RNA chaperone-Hfq assisted RNA annealing strategy for the sensitive detection of the intermediate product, oligouridylated RNA, in a genetic regulation process was developed. Benefiting from the high binding affinity of Hfq for the probe and the target, the sensitive determination of oligouridylated RNA in cell lysis and human cervical cancer (HeLa) cells was successfully achieved. This study has also revealed that the Hfq assisted RNA annealing strategy can be further extended and applied in specific microRNA analysis, and RNA related tumorigenicity and disease diagnosis.

Reliable Förster Resonance Energy Transfer Probe Based on Structure-Switching DNA for Ratiometric Sensing of Telomerase in Living Cells.

In situ detection and monitoring of telomerase is of great importance as it is a relatively specific cancer target. However, the complexity of the biological system makes it difficult for the nanoprobe to keep absolutely stable and have a low background in living cells. This study designs a probe termed Förster resonance energy transfer (FRET) nanoflare to achieve ratiometric fluorescent detection of intracellular telomerase with higher specificity, which can effectively resist the disturbance from DNase I and GSH, etc. The probe is composed of a gold nanoparticle (AuNP) which is functioned with telomerase primer sequences (TS) and flares fluorescently labeled donors and acceptors at two terminals. In the presence of telomerase, flares are displaced from the primer sequences and form hairpin structures, so that the donors and acceptors are brought into close proximity, resulting in high FRET efficiency. The probe exhibits good performance for efficiently distinguishing tumor cells from normal cells and monitoring the change of intracellular telomerase activity during treatment with telomerase-related drugs, showing great potential for cancer diagnosis and estimating therapeutic effect.

CD3ε of a pan T cell marker involved in mouse Aspergillus fumigatus keratitis.

AIM: To explore whether CD3ε is involved in the adaptive immunity of Aspergillus fumigatus (A. fumigatus) keratitis in mice and the role of innate and adaptive immunity in it. METHODS: Mice models of A. fumigatus keratitis were established by intra-stromal injection and corneal epithelial scratching. Subconjunctival injections of natamycin, wedelolactone, LOX-1 inhibitor (poly I) or Dectin-1 inhibitor (laminarin) were used to treat mice with A. fumigatus keratitis. Mice were pretreated by intraperitoneal injection of anti-mouse CD3ε. We observed the corneal infection of mice under the slit lamp microscope and made a clinical score. The protein expression of CD3ε and interleukin-10 (IL-10) was determined by Western blotting. RESULTS: With the disease progresses, the degree of corneal opacity and edema augmented. In the intra-stromal injection models, CD3ε protein expression began to increase significantly on the 2nd day. However, in the scraping epithelial method models, CD3ε only began to increase on the 3rd day. After natamycin treatment, the degree of corneal inflammation in mice was significantly attenuated on the 3rd day. After wedelolactone treatment, the severity of keratitis worsened. And the amount of CD3ε protein was also reduced, compared with the control group. By inhibiting LOX-1 and Dectin-1, there was no significant difference in CD3ε production compared with the control group. After inhibiting CD3ε, corneal ulcer area and clinical score increased, and IL-10 expression was downregulated. CONCLUSION: As a pan T cell marker, CD3ε participate in the adaptive immunity of A. fumigatus keratitis in mice. In our mice models, the corneas will enter the adaptive immune stage faster. By regulating IL-10, CD3ε exerts anti-inflammatory and repairs effects in the adaptive immune stage.

[Delivery of megawatts high energy laser pulse with large core diameter silica fiber and its application in dual-wavelength laser-ablation laser-induced breakdown spectroscopy].

To resolve the contradiction between spatial resolution and analysis sensitivity in single pulse laser-induced breakdown spectroscopy (LIBS), a study on dual-wavelength laser-ablation laser-induced breakdown spectroscopy (LA-LIBS) was carried out by using one Nd : YAG laser which was capable of two laser beam outputs with different wavelengths, where, the second harmonic output, 532 nm laser beam, was used as laser-ablation source, and the fundamental output, 1064 nm laser beam, was delivered with a large core diameter silica fiber to realize nanoseconds time-delay and then used to breakdown the ablated samples. Two laser beams were orthogonally arranged to realize element analysis with high spatial resolution and high sensitivity. Some key techniques on the coupling of 1064 nm laser beam into fiber, the collimation of laser at the fiber end and re-focusing of the laser beam were studied. The energy delivery capabilities of four fibers of different types were studied and the maximum values were determined experimentally. A Q-switched laser pulse with 15 mJ pulse energy was successfully delivered by selecting a 50 meter long silica fiber with 800 microm core diameter and 0. 39 numerical aperture. And 250 ns time-delay was realized. A copper alloy was analyzed by spectra with current established LA-LIBS system and the possibility of realizing dual-wavelength LA-LIBS analysis based on one Nd : YAG laser was demonstrated experimentally. In this technique, only one Nd: YAG laser was required to carry out spectral analysis. It has a few advantages, such as simple equipment structure, and being convenient to miniaturize the whole system etc. This dual-wavelength LA-LIBS technique was suitable for in-situ elements microanalysis for different samples with both high spatial resolution and high sensitivity.

Triple signal amplification strategy for ultrasensitive in situ imaging of intracellular telomerase RNA.

Abnormal upregulation of telomerase RNA (TR) is a hallmark event at various stages of tumor progression, providing a universal marker for early diagnosis of cancer. Here, we have developed a triple signal amplification strategy for in situ visualization of TR in living cells, which sequentially incorporated the target-initiated strand displacement circuit, multidirectional rolling circle amplification (RCA), and Mg2+ DNAzyme-mediated amplification. All oligonucleotide probes and cofactors were transfected into cells in one go, and then escaped from lysosomes successfully. Owing to the specific base pairing, the amplification cascades could only be triggered by TR and performed as programmed, resulting in a satisfactory signal-to-background ratio. Especially, the netlike DNA structure generated by RCA encapsulated high concentrations of DNAzyme and substrates (FQS) in a local region, thereby improving the reaction efficiency and kinetics of the third amplification cycle. Under optimal conditions, the proposed method exhibited ultrasensitive detection of TR mimic with a detection limit at pM level. Most importantly, after transfection with the proposed sensing platform, tumor cells can be easily distinguished from normal cells based on TR abundance-related fluorescence signal, providing a new insight into initial cancer screening.

[Clinical efficacy and safety of FP-7 Ahmed glaucoma valve implantation in neurovascular glaucoma patients].

OBJECTIVE: To evaluate the efficacy and safety of FP-7 Ahmed glaucoma valves (AGV) implantation in neurovascular glaucoma (NVG) as the first choice of surgery. METHODS: This retrospective, comparative case series study collected a total of 36 eyes of 36 patients with neurovascular glaucoma who underwent AGV implantation in Zhongshan Ophthalmic Center from January 2009 to June 2010. Change of intraocular pressure (IOP), the best corrected visual acuity, numbers of anti-glaucoma medication, success rate and postoperative complications were followed up at day 1, week 1, month 1, and every 3 months after surgery. Complete success of surgery was rated as reduction of IOP ≥ 30% without medication and those who failed to meet criteria was rated as partial success. Data were analyzed by paired Student t-test for IOP, rank sum test for paired non-parametric numbers of medication, and repeated measures analysis of variance for comparison of IOP between different time points using SPSS 13.0. RESULTS: Compared with pre-operation, IOP was significant (F = 9.26, P < 0.05) decreased after surgery with FP-7 AGV implantation (39.5 ± 9.7) mm Hg (1 mm Hg = 0.133 kPa) vs (9.2 ± 8.9), (11.8 ± 3.8), (13.7 ± 4.8), (16.9 ± 5.3), (16.9 ± 6.8) mm Hg at day 1, week 1, month 1, month 3 and the last following-up of post-operation, respectively. The numbers of anti-glaucoma medication were significantly (Z = 6.764, P < 0.05) reduced from 4.0 (1-6) of pre-operation to 1.0 (1-3) of post-operation. At the last following up, the complete success rate after FP-7 AGV implantation was 80.6%, and qualified success rate was 91.7%. The postoperative complications including occlusion of the drainage tube, exposure of the drainage tube, shallow anterior chamber and encapsulated cystic blebs around the plate were controlled with additional treatment. CONCLUSIONS: The clinical outcome indicated that the implantation of FP-7 AGV has a stable IOP lowering effect and fewer complications, which can be considered as one of the first choices for management of NVG.

Leukocyte related parameters in older adults with metabolically healthy and unhealthy overweight or obesity.

It remains unclear whether leukocyte-related parameters could be used as biomarkers to differentiate metabolically unhealthy overweight/obesity (MUO) from metabolically healthy overweight/obesity (MHO). We aimed to examine the differences in the distribution of leukocyte-related parameters between older adults with MHO and MUO and the correlations of leukocyte-related parameters with individual components of metabolic abnormality. In the Weitang Geriatric Diseases Study on older Chinese adults aged 60 years or above, 404 individuals with MHO and 480 with MUO contributed to the analysis. Overweight/obesity was defined as body mass index (BMI) of 25 kg/m2 or more. MHO and MUO were discriminated based on the Adult Treatment Panel III (ATP III) criteria. Leukocyte-related parameters were assessed using an automated hematology analyzer. All leukocyte-related parameters except monocytes were elevated in MUO group compared with MHO group (all P < 0.05). The prevalence of MUO increased by 24% with each 109/L increase of leukocytes after adjusting for confounders in the multiple-adjusted model (P < 0.01) and each unit elevation of other parameters except lymphocytes and monocytes were significantly associated with the presence of MUO (all P < 0.01). Trend tests revealed a linear trend for the association between MUO and all the leukocyte-related parameters (all P for trend < 0.05). Significant interactions between leukocyte-related parameters and sex on the presence of MUO were observed (all P value for interaction < 0.05). Higher leukocyte-related parameters were found in patients with MUO than those with MHO and were associated with higher prevalence of MUO which seems to be sex-dependent. Further studies are needed to see whether these parameters could be used as biomarkers for the screening or diagnosis for MUO in clinical or public health practice.

Living-Cell MicroRNA Imaging with Self-Assembling Fragments of Fluorescent Protein-Mimic RNA Aptamer.

As the cellular roles of RNA abundance continue to increase, there is an urgent need for the corresponding tools to elucidate native RNA functions and dynamics, especially those of short, low-abundance RNAs in live cells. Fluorescent RNA aptamers provide a useful strategy to create the RNA tag and biosensor devices. Corn, which binds with 3,5-difluoro-4-hydroxybenzylidene-imidazolinone-2-oxime (DFHO), is a good candidate for the RNA tag because of its enhanced photostability and red-shifted spectrum. Herein, we report for the first time the utilization of Corn as a split aptamer system, combined with RNA-initiated fluorescence complementation (RIFC), for monitoring RNA self-assembly and sensing microRNA. In this platform, the 28-nt Corn was divided into two nonfunctional halves (named probe I and probe II), and an additional target RNA recognition and stem part was introduced in each probe. The target RNA can trigger the self-assembly reconstitution of the Corn's G-quadruplex scaffold for DFHO binding and turn-on fluorescence. These probes can be transfected stably into mammalian cells and deliver the light-up fluorescent response to microRNA-21 (miR-21). Significantly, the probes have good photostability, with minimal fluorescence loss after continuous irradiation, and can be used for imaging of miR-21 in living mammalian cells. The proposed method is universal and could be applied to the sensing of other tumor-associated RNAs, including messenger RNA and noncoding RNA, as well as for monitoring RNA/RNA interactions. The Corn-based splitting aptamers show promising potential in the real-time visualization and mechanistic analysis of nucleic acids.

Platelet parameters in Chinese older adults with metabolic syndrome.

PURPOSE: We aimed to examine the associations of platelet parameters with the presence of metabolic syndrome in community-dwelling older Chinese adults. METHODS: Study sample was from the Weitang Geriatric Diseases Study, which included 4338 individuals aged 60 years or above. The mean age of the participants was 68 years. Metabolic syndrome was defined based on the Adult Treatment Panel III criteria. Platelet parameters were assessed using an automated hematology analyzer. Multiple logistic regression models were fitted to examine relationships between the platelet parameters and the presence of metabolic syndrome after adjusting for potential confounders. RESULTS: The adjusted odds ratio (95% CI) of metabolic syndrome for the highest quartile of platelet parameters (platelet count, mean platelet volume, plateletcrit, platelet distribution width, platelet larger cell ratio) when compared to the lowest quartile were 1.32 (1.06, 1.64), 1.00 (0.81, 1.24), 1.37 (1.10, 1.71), 1.45 (1.14, 1.83), 1.11 (0.89, 1.39), respectively. Hypertension and diabetes modified the relationship between platelet distribution width and metabolic syndrome with the associations being significant in hypertensive and non-diabetic groups. The levels of platelet distribution width increased with the risk of metabolic syndrome in men but not in women. CONCLUSION: The levels of platelet count, plateletcrit and platelet distribution width increased in older adults with metabolic syndrome, suggesting that these parameters may be useful biomarkers for further risk appraisal of metabolic syndrome in aged population.

Leukocyte-related parameters in older adults with metabolic syndrome.

PURPOSE: We aimed to examine the association between leukocyte-related parameters and the risk of metabolic syndrome (MetS) in community-dwelling older Chinese adults, with a special focus on assessing the diagnostic ability of leukocyte-related parameters in detecting MetS and the potential interaction effect of sex in the leukocyte-MetS relationship. METHODS: Study sample was from the Weitang Geriatric Diseases Study, which included 4579 individuals aged 60 years or above. MetS was diagnosed based on the Adult Treatment Panel III criteria. Leukocyte-related parameters were assessed using an automated hematology analyzer. RESULTS: The adjusted odds ratio (95% confidence interval (CI)) of MetS for the highest quartile of leukocyte-related parameters (leukocyte, lymphocyte, neutrophil, monocyte, eosinophil, and basophil), when compared with the lowest quartile were 2.87 (2.30, 3.59), 2.69 (2.15, 3.36), 2.09 (1.67, 2.62), 2.12 (1.71, 2.64), 1.62 (1.31, 2.00), and 1.36 (1.11, 1.65), respectively. Adding leukocyte, lymphocyte, monocyte, and neutrophil to a model containing conventional risk factors improved risk prediction for MetS. Furthermore, significant interactions between leukocyte, monocyte, neutrophil, and sex on MetS were observed (all P value for interaction <0.01). CONCLUSION: The numbers of total leukocytes, lymphocyte, monocyte, neutrophil, and eosinophil counts were elevated in older adults with MetS, suggesting that leukocyte-related parameters may be meaningful biomarkers for MetS. Adding leukocyte-related parameters to the conventional models increased the ability of predicting MetS among older adults. These parameters may be useful biomarkers for further risk appraisal of MetS in older adults.

A self-powered 3D DNA walker with programmability and signal-amplification for illuminating microRNA in living cells.

Based on the structural programmability and spatial addressability of DNA nanodevices, a target-triggered, enzyme-free 3D DNA walker, comprising of hairpin DNA assembled gold nanoparticles with a local catalytic hairpin assembly reaction, was developed for the highly sensitive detection of intracellular tumor-associated microRNAs.

NIR-Activated Spatiotemporally Controllable Nanoagent for Achieving Synergistic Gene-Chemo-Photothermal Therapy in Tumor Ablation.

A rational combination of different therapeutic modalities within one single nanostructure is promising to enhance the therapeutic response, especially to achieve a synergistic therapeutic efficacy for tumor treatment. Herein, a near-infrared (NIR) photothermally activated nanoagent, which could achieve a spatially controllable codelivery of different curative molecules and a temporally controlled responsive release, was designed to perform effective gene-chemo-photothermal therapy of malignant tumors. The nanoagent consisted of a gold nanorod (AuNR) functionalized with mPEG, DNA, and small interfering RNA (siRNA). With the aid of aptamer AS1411-mediated recognition and endocytosis, the nanoagents were selectively delivered into cancer cells; subsequently, the photothermal conversion of AuNRs happened while under NIR irradiation, which successfully achieved an effective photothermal therapy, induced dehybridization of DNA duplexes, and simultaneously released doxorubicin (DOX) and siRNA. Then, the released siRNA silenced the expression of the multidrug resistance associated protein 1 (MRP1), the primary cause of the undesirable expelling of DOX in PC-3 cells, yielding a remarkable improvement in the efficiency of gene-chemo therapy. All of the results of in vitro and in vivo studies revealed that our prepared nanoagents exhibited an excellent performance in synergistic gene-chemo-photothermal therapy and successfully inhibited tumor growth. This work provides an interesting concept of a nanoscale therapeutic agent in achieving a dramatically enhanced therapeutic ability for tumor ablation, which benefits from the spatiotemporally controllable properties and the synergistic combination of chemotherapy, gene therapy, and photothermal therapy in one single nanoagent.

Compound heterozygous mutations in CYP1B1 gene leads to severe primary congenital glaucoma phenotype.

AIM: To identify the novel mutation alleles in the CYP1B1 gene of primary congenital glaucoma (PCG) patients at Shandong Province of China, and investigate their correlation with glaucomatous features. METHODS: The DNA from the peripheral blood of 13 congenital glaucoma patients and 50 ethnically matched healthy controls from the affiliated hospital of Qingdao University were extracted. The coding region of the CYP1B1 gene was amplified by PCR and direct DNA sequencing was performed. Disease causing-variants were analyzed by comparing the sequences and the structures of wild type and mutant CYP1B1 proteins by PyMOL software. RESULTS: Two missense mutations, including A330F caused by c.988G>T&c.989C>T, and R390H caused by c.1169G>A, were identified in one of the 13 PCG patients analyzed in our study. A330F mutation was observed to be novel in the Chinese Han population, which dramatically altered the protein structure of CYP1B1 gene, including the changes in the ligand-binding pocket. Furthermore, R390H mutation caused the changes in heme-protein binding site of this gene. In addition, the clinical phenotype displayed by PCG patient with these mutations was more pronounced than other PCG patients without these mutations. Multiple surgeries and combined drug treatment were not effective in reducing the elevated intraocular pressure in this patient. CONCLUSION: A novel A330F mutation is identified in the CYP1B1 gene of Chinese PCG patient. Moreover, in combination with other mutation R390H, this PCG patient shows significant difference in the CYP1B1 protein structure, which may specifically contribute to severe glaucomatous phenotype.

In situ imaging and interfering Dicer-mediated cleavage process via a versatile molecular beacon probe.

A novel versatile locked nucleic acid modified molecular beacon probe (LNA-MB) was developed for imaging intracellular precursor miRNAs (pre-miRNAs) and disturbing Dicer-mediated cleavage process. The target recognition reaction between the smart probe and pre-miRNA can not only induce the conformational changes of probe and block the Dicer cleavage site, but also inhibit the cleavage process, and then achieve down-regulation of miRNA expression. Simultaneously, the target recognition reaction broke the fluorescence resonance energy transfer (FRET) between fluorophore donor FAM and acceptor TAMRA, which were labelled on the LNA-MB probe, further induced the relevant change of fluorescence signal, and then achieved imaging analysis of pre-miRNA and inhibition events in situ. Both in vitro and in single living cell studies showed that the versatile probes exhibited a remarkable performance in targeting with pre-miRNA-21, and nearly 65% downregulation of mature miRNA-21 was achieved with 100 nM probes. All investigations demonstrate that the proposed strategy represents a promising alternative for regulating and inhibiting endogenous disease-associated RNAs, then further for achieving therapeutic outcomes in personalized treatments.

Effects of chronic elevated intraocular pressure on parameters of optical coherence tomography in rhesus monkeys.

AIM: To determine the progression of parameters from optical coherence tomography (OCT) in chronic elevated intraocular pressure (IOP) monkeys. METHODS: A chronic elevated IOP model of rhesus monkeys was induced by laser photocoagulation. Representative OCT parameters, including the average and four-quadrant retinal nerve fiber layer (RNFL) thickness, and parameters from optic nerve head (ONH) analysis were collected before and after laser treatments biweekly for up to 28wk. The performance of each parameter for early progression detection was analyzed. The progressive trends toward elevated IOP were analyzed using a linear mixed-effects model. RESULTS: There were 10 successfully maintained high IOP eyes in 7 monkeys. The follow-up time was 24±5.37wk. With cumulative IOP elevation, the cup area, rim area and C/D area ratio were statistically significantly changed as early as 2wk after elevated IOP induction (P<0.05). The quadrant RNFL thickness changed at 6wk after high IOP induction, and the superior and inferior RNFL thicknesses exhibited more obvious reductions than other quadrants. The average RNFL thickness was the last one to show a significant decrease at 8wk. CONCLUSION: The parameters of ONH are most sensitive to elevated IOP in a primate glaucomatous model. These findings suggest that we should focus on those parameters instead of RNFL thickness in patients with elevated IOP, as they might present with earlier glaucomatous changes.