Precise and Programmable Detection of Mutations Using Ultraspecific Riboregulators.

The ability to identify single-nucleotide mutations is critical for probing cell biology and for precise detection of disease. However, the small differences in hybridization energy provided by single-base changes makes identification of these mutations challenging in living cells and complex reaction environments. Here, we report a class of de novo-designed prokaryotic riboregulators that provide ultraspecific RNA detection capabilities in vivo and in cell-free transcription-translation reactions. These single-nucleotide-specific programmable riboregulators (SNIPRs) provide over 100-fold differences in gene expression in response to target RNAs differing by a single nucleotide in E. coli and resolve single epitranscriptomic marks in vitro. By exploiting the programmable SNIPR design, we implement an automated design algorithm to develop riboregulators for a range of mutations associated with cancer, drug resistance, and genetic disorders. Integrating SNIPRs with portable paper-based cell-free reactions enables convenient isothermal detection of cancer-associated mutations from clinical samples and identification of Zika strains through unambiguous colorimetric reactions.

Thermal-plex: fluidic-free, rapid sequential multiplexed imaging with DNA-encoded thermal channels.

Multiplexed fluorescence imaging is typically limited to three- to five-plex on standard setups. Sequential imaging methods based on iterative labeling and imaging enable practical higher multiplexing, but generally require a complex fluidic setup with several rounds of slow buffer exchange (tens of minutes to an hour for each exchange step). We report the thermal-plex method, which removes complex and slow buffer exchange steps and provides fluidic-free, rapid sequential imaging. Thermal-plex uses simple DNA probes that are engineered to fluoresce sequentially when, and only when, activated with transient exposure to heating spikes at designated temperatures (thermal channels). Channel switching is fast (<30 s) and is achieved with a commercially available and affordable on-scope heating device. We demonstrate 15-plex RNA imaging (five thermal × three fluorescence channels) in fixed cells and retina tissues in less than 4 min, without using buffer exchange or fluidics. Thermal-plex introduces a new labeling method for efficient sequential multiplexed imaging.

Percutaneous Intra-arterial Hyaluronidase Injection for Hyaluronic Acid Filler Embolism Threatening Skin Barrier Integrity: Implementation of a Stepwise Treatment Protocol.

BACKGROUND: Hyaluronic acid (HA) filler-induced vascular embolism that threatens skin integrity is an urgent situation. There is increasing evidence that percutaneous intra-arterial hyaluronidase injection is an effective therapeutic technique for it. However, until now, there is a lack of a unifying protocol about the technique. OBJECTIVES: This study aims to provide a conclusion of percutaneous intra-arterial hyaluronidase injection along with adjunctive measures on the treatment of occlusions precipitated by HA-based filler and develop a stepwise treatment protocol. METHODS: We searched PubMed for peer-reviewed studies, consensus statements, case series, and case reports using a variety of keywords. RESULTS: High-dose, pulsed hyaluronidase is the mainstay for the treatment of HA filler-induced embolism, but percutaneous intra-arterial hyaluronidase injection is a more effective technique. Until now, hyaluronidase is injected into three arteries percutaneously, including facial artery, supratrochlear artery, and superficial temporal artery. Furthermore, the adjunctive measures that may optimize clearance of an occlusion and/or skin barrier repair such as the use of image guidance and CGF should be considered. CONCLUSION: Vascular occlusions that threaten skin integrity are an urgent matter which requires accurate diagnosis and effective intervention. Percutaneous intra-arterial hyaluronidase injection along with adjunctive measures performed in a stepwise manner is key to an optimal outcome. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Fiber-sensor alignment based on surface microstructures.

Conventional methods have relied on specialized imaging equipment and advanced fabrication process to solve the problem of accurately aligning a microsensor to an optical fiber which is critical for its detection efficiency. To dramatically lower the barrier to high-precision alignment, we present a technique much easier to implement and much lower in cost. By fabricating replicable alignment and proximity structures on the surface of the sensor chip, we can achieve accurate alignment and position the fiber tip very close to the sensor without damaging it. We introduce an easy setup to examine the alignment result and demonstrate accurate alignment of dummy sensors as small as 5µm×5µm. We use our alignment method to realize efficient input coupling for a superconducting transition-edge sensor as an example of fruitful adoption in many possible applications.

Environmental chemical TCPOBOP disrupts milk lipid homeostasis during pregnancy and lactation.

Humans are exposed to different kinds of environmental contaminants or drugs throughout their lifetimes. The widespread presence of these compounds has raised concerns about the consequent adverse effects on lactating women. The constitutive androstane receptor (CAR, Nr1i3) is known as a xenobiotic sensor for environmental pollution or drugs. In this study, the model environmental chemical 1, 4-bis [2-(3, 5-dichloropyridyloxy)] benzene, TCPOBOP (TC), which is a highly specific agonist of CAR, was used to investigate the effects of exogenous exposure on lactation function and offspring health in mice. The results revealed that TC exposure decreased the proliferation of mammary epithelial cells during pregnancy. This deficiency further compromised lobular-alveolar structures, resulting in alveolar cell apoptosis, as well as premature stoppage of the lactation cycle and aberrant lactation. Furthermore, TC exposure significantly altered the size and number of milk lipid droplets, suggesting that TC exposure inhibits milk lipid synthesis. Additionally, TC exposure interfered with the milk lipid metabolism network, resulting in the inability of TC-exposed mice to efficiently secrete nutrients and feed their offspring. These findings demonstrated that restricted synthesis and secretion of milk lipids would indirectly block mammary gland form and function, which explained the possible reasons for lactation failure and retarded offspring growth.

Aligning Superconducting Transition-Edge Sensors by Reflected Wave Intensity Measurement.

It is critical to accurately align a quantum photon detector such as a superconducting transition-edge sensor (TES) to an optical fiber in order to optimize its detection efficiency. Conventionally, such alignment requires advanced infrared imaging equipment or sophisticated microfabrication. We introduce a novel technique based on the simple idea of reflected wave intensity measurement which allows to determine the boundary of the sensor and align it accurately with the fiber. By routing a light wave through an optical fiber for normal incidence on the surface of the sensor chip, and separating the reflected wave coupled back into the fiber from the input signal with a circulator, we can observe the variation in the reflected wave intensity when the beam spot of the fiber crosses the boundary between the sensor and substrate that have different reflectivity, and adjust the position of the fiber such that its output falls on the sensor. We evaluate quantitatively the precision of our alignment method, as well as the conditions that must be met to avoid photon loss caused by light beam divergence. After demonstrating the working principle of our scheme and verifying the alignment result experimentally, we employ it for efficient input signal coupling to a TES device, which is used for photon-number-resolving measurement to showcase the successful application of our alignment method in practice. Relying on only ordinary and widely used optical elements that are easy to operate and low in cost, our solution is much less demanding than conventional methods. Dramatically easier to implement and not restricted by the detection mechanism of the sensor, it is accessible to a much broader community.

Efficacy of Percutaneous Superficial Temporal Arterial Hyaluronidase Injection for Hyaluronic Acid Filler-Induced Necrosis of Frontotemporal Skin and/or the Ipsilateral Scalp With Subsequent Alopecia.

BACKGROUND: Necrosis of frontotemporal skin and/or the ipsilateral scalp with subsequent alopecia after hyaluronic acid (HA) filler injection into the temple is rare complications with superficial temporal artery embolization are suspected as the major pathological mechanism. The main treatment currently is intralesional hyaluronidase (HAase) injection, but the effectiveness of percutaneous superficial temporal arterial HAase injection still lacks consensus. OBJECTIVES: To investigate the effectiveness of superficial temporal arterial HAase injection in dissolving HA filler-induced necrosis of frontotemporal skin and/or the ipsilateral scalp with subsequent alopecia. METHODS: Five recent clinical cases with necrosis of frontotemporal skin and/or the ipsilateral scalp with subsequent alopecia after HA filler injection into the temple were analyzed retrospectively. The patients underwent HAase injection via superficial temporal artery combined with adjunctive treatments, and the clinical progress was observed. RESULTS: Significant improvement was observed in terms of necrosis of frontotemporal skin and the ipsilateral scalp after treatment, and the patients were relieved of their clinical symptoms. Alopecia occurred approximately 1 to 2 weeks after HA filler injection, and the well-defined alopecia areas were formed 15 to 20 days after HAase injection. Patients were followed for 3 to 6 months. During follow-up, the skin lesions of all patients were restored to near normal appearance. Hair regrowth was observed 2 to 3 months after HAase treatment, and hair density nearly reached the normal level 3 to 4 months later. CONCLUSIONS: Percutaneous superficial temporal arterial HAase injection is an effective treatment option for HA filler-induced necrosis of frontotemporal skin and/or the ipsilateral scalp with subsequent alopecia.

SRY is a Key Mediator of Sexual Dimorphism in Hepatic Ischemia/Reperfusion Injury.

OBJECTIVES: To identify the role and mechanism of a male specific gene, SRY, in I/R-induced hepatic injury. BACKGROUND: Males are more vulnerable to I/R injury than females. However, the mechanism of these sex-based differences remains poorly defined. METHODS: Clinicopathologic data of patients who underwent hepatic resection were identified from an international multi-institutional database. Liver specific SRY TG mice were generated, and subjected to I/R insult with their littermate WT controls in vivo. In vitro experiments were performed by treating primary hepatocytes from TG and WT mice with hypoxia/reoxygen-ation stimulation. RESULTS: Clinical data showed that postoperative aminotransferase level, incidence of overall morbidity and liver failure were markedly higher among 1267 male versus 508 female patients who underwent hepatic resection. SRY was dramatically upregulated during hepatic I/R injury. Overexpression of SRY in male TG mice and ectopic expression of SRY in female TG mice exacerbated liver I/R injury compared with WTs as manifested by increased inflammatory reaction, oxidative stress and cell death in vivo and in vitro. Mechanistically, SRY interacts with Glycogen synthase kinase-3ß (GSK-3ß) and ß-catenin, and promotes phosphorylation and degradation of ß-catenin, leading to suppression of the downstream FOXOs, and activation of NF-κBand TLR4 signaling. Furthermore, activation of ß-catenin almost completely reversed the SRYoverexpression-mediated exacerbation of hepatic I/R damage. CONCLUSIONS: SRY is a novel hepatic I/R mediator that promotes hepatic inflammatory reaction, oxidative stress and cell necrosis via inhibiting Wnt/ß-catenin signaling, which accounts for the sex-based disparity in hepatic I/R injuries.

Understanding DNA interactions in crowded environments with a coarse-grained model.

Nucleic acid interactions under crowded environments are of great importance for biological processes and nanotechnology. However, the kinetics and thermodynamics of nucleic acid interactions in a crowded environment remain poorly understood. We use a coarse-grained model of DNA to study the kinetics and thermodynamics of DNA duplex and hairpin formation in crowded environments. We find that crowders can increase the melting temperature of both an 8-mer DNA duplex and a hairpin with a stem of 6-nt depending on the excluded volume fraction of crowders in solution and the crowder size. The crowding induced stability originates from the entropic effect caused by the crowding particles in the system. Additionally, we study the hybridization kinetics of DNA duplex formation and the formation of hairpin stems, finding that the reaction rate kon is increased by the crowding effect, while koff is changed only moderately. The increase in kon mostly comes from increasing the probability of reaching a transition state with one base pair formed. A DNA strand displacement reaction in a crowded environment is also studied with the model and we find that rate of toehold association is increased, with possible applications to speeding up strand displacement cascades in nucleic acid nanotechnology.

Magnetic-assisted laparoscopic liver transplantation in swine.

BACKGROUND: Although laparoscopic technology has achieved rapid development in the surgical field, it has not been applied to liver transplantation, primarily because of difficulties associated with laparoscopic vascular anastomosis. In this study, we introduced a new magnetic-assisted vascular anastomosis technique and explored its application in laparoscopic liver transplantation in pigs. METHODS: Two sets of magnetic vascular anastomosis rings (MVARs) with different diameters were developed. One set was used for anastomosis of the suprahepatic vena cava (SHVC) and the other set was used for anastomosis of the infrahepatic vena cava (IHVC) and portal vein (PV). Six laparoscopic orthotopic liver transplantations were performed in pigs. Donor liver was obtained via open surgery. Hepatectomy was performed in the recipients through laparoscopic surgery. Anastomosis of the SHVC was performed using hand-assisted magnetic anastomosis, and the anastomosis of the IHVC and PV was performed by magnetic anastomosis with or without hand assistance. RESULTS: Liver transplants were successfully performed in five of the six cases. Postoperative ultrasonographic examination showed that the portal inflow was smooth. However, PV bending and blood flow obstruction occurred in one case because the MVARs were attached to each other. The durations of loading of MVAR in the laparoscope group and manual assistance group for IHVC and PV were 13 ± 5 vs. 5 ± 1 min (P < 0.01) and 10 ± 2 vs. 4 ± 1 min (P < 0.05), respectively. The durations of MVAR anastomosis in the laparoscope group and manual assistance group for IHVC and PV were 5 ± 1 vs. 1 ± 1 min (P < 0.01), and 5 ± 1 vs. 1 ± 1 min (P < 0.01), respectively. The anhepatic phase was 43 ± 4 min in the laparoscope group and 23 ± 2 min in the manual assistance group (P < 0.01). CONCLUSIONS: Our study showed that magnetic-assisted laparoscopic liver transplantation can be successfully carried out in pigs.

Identification of CDKL3 as a critical regulator in development of glioma through regulating RRM2 and the JNK signaling pathway.

Glioma is one of the most commonly diagnosed intracranial malignancies. The molecular mechanism underlying the development of glioma is still largely unknown. In this study, we present the first report concerning the function and mechanism of cyclin-dependent kinase-like 3 (CDKL3) in the development and prognosis of glioma. It is shown that CDKL3 was upregulated in glioma tissues and could independently predict poor prognosis of patients. Silencing CDKL3 in glioma cells could inhibit cell proliferation and migration and induce cell apoptosis and cell cycle arrest, whereas the overexpression of CDKL3 promoted cell proliferation. The in vivo experiments also indicated that knockdown of CDKL3 significantly suppressed tumor growth of glioma. Gene expression profiling of CDKL3 knockdown U87 cells identified RRM2 as a potential target of CDKL3, which was proved to have direct interaction with CDKL3. Given similar effects on glioma development with CDKL3, knockdown of RRM2 could rescue the effects of CDKL3 overexpression on glioma cells. Moreover, knockdown of CDKL3 or RRM2 suppressed the activity of JNK signaling, whereas CDKL3 overexpression produced the opposite effect. In conclusion, our results identified CDKL3 as a promotor for glioma, probably through the regulation of RRM2 and activation of the JNK signalling pathway, highlighting the significance of CDKL3 as a promising therapeutic target of glioma.

Long non-coding RNA ROR recruits histone transmethylase MLL1 to up-regulate TIMP3 expression and promote breast cancer progression.

BACKGROUND: As a significant cause of cancer deaths worldwide, breast cancer continues to be a troublesome malignancy. Long non-coding RNAs (lncRNAs) have been implicated in the development of breast cancer. Abnormal methylation has been associated with unfavorable breast cancer prognosis. Herein, the current study aimed to elucidate the role of lncRNA ROR in breast cancer. METHODS: RT-qPCR was performed to determine whether lncRNA ROR was highly expressed in breast cancer tissues, while lncRNA ROR expression was detected in both the nuclear and cytoplasm of breast cancer cells. MCF-7 cells were subsequently introduced with oe-lncRNA ROR, sh-lncRNA ROR to explore the effects of lncRNA ROR on cell proliferation, invasion and apoptosis. RESULTS: RIP, RNA pull-down and ChIP assays provided evidence suggesting that lncRNA ROR recruited transmethylase MLL1 to promote H3K4 trimethylation that enhanced TIMP3 transcription. The rescue experiments demonstrated that lncRNA ROR knockdown could inhibit the progression of breast cancer via the downregulation of TIMP3. Finally, the in vivo experiment findings consistently highlighted the suppressive effects of lncRNA ROR silencing on tumor growth. CONCLUSION: Taken together, our study demonstrates that silencing of lncRNA ROR inhibits breast cancer progression via repression of transmethylase MLL1 and TIMP3, emphasizing the potential of lncRNA ROR as a novel target against breast cancer.

An eight-mRNA signature outperforms the lncRNA-based signature in predicting prognosis of patients with glioblastoma.

BACKGROUND: The prognosis of the glioblastoma (GBM) is dismal. This study aims to select an optimal RNA signature for prognostic prediction of GBM patients. METHODS: For the training set, the long non-coding RNA (lncRNA) and mRNA expression profiles of 151 patients were downloaded from the TCGA. Differentially expressed mRNAs (DEGs) and lncRNAs (DE-lncRNAs) were identified between good prognosis and bad prognosis patients. Optimal prognostic mRNAs and lncRNAs were selected respectively, by using univariate Cox proportional-hazards (PH) regression model and LASSO Cox-PH model. Subsequently, four prognostic scoring models were built based on expression levels or expression status of the selected prognostic lncRNAs or mRNAs, separately. Each prognostic model was applied to the training set and an independent validation set. Function analysis was used to uncover the biological roles of these prognostic DEGs between different risk groups classified by the mRNA-based signature. RESULTS: We obtained 261 DEGs and 33 DE-lncRNAs between good prognosis and bad prognosis patients. A panel of eight mRNAs and a combination of ten lncRNAs were determined as predictive RNAs by LASSO Cox-PH model. Among the four prognostic scoring models using the eight-mRNA signature or the ten-lncRNA signature, the one based on the expression levels of the eight mRNAs showed the greatest predictive power. The DEGs between different risk groups using the eight prognostic mRNAs were functionally involved in calcium signaling pathway, neuroactive ligand-receptor interaction pathway, and Wnt signaling pathway. CONCLUSION: The eight-mRNA signature has greater prognostic value than the ten-lncRNA-based signature for GBM patients based on bioinformatics analysis.

A novel preoperative scoring system to predict technical difficulty in laparoscopic splenectomy for non-traumatic diseases.

BACKGROUND: Laparoscopic splenectomy (LS) has been proven to be a safe and advantageous procedure. To ensure that resections of appropriate difficulty are selected, an objective preoperative grading of difficulty is required. We aimed to develop a predictive difficulty grading of LS based on intraoperative complications. METHODS: A total of 272 non-traumatic patients who underwent LS were identified from a regional medical center. Patients were randomized into a training cohort (n = 222) and a validation cohort (n = 50). Data on demographics, medical and surgical history, operative and pathological characteristics, and postoperative outcome details were collected. Univariate and multivariate analyses of risk factors for intraoperative complications were performed to develop a difficulty scoring system. The Spearman correlation coefficient was used to evaluate the relationship between the difficulty grading score and intraoperative outcomes. Receiver operating characteristic (ROC) curve was used to evaluate the discriminatory power of this scoring system. RESULTS: Three preoperative factors (spleen weight, esophagogastric varices, and INR) had a significant effect on operative time, bleeding, and conversion to open surgery. We created a difficulty grading score with three levels of difficulty: low (≤ 4 points), medium (5-6 points), and high (≥ 7 points), based on the three preoperative parameters. The correlation was highly significant (P < 0.01) according to Spearman's correlation. The area under the ROC curve was 0.695 (95% CI 0.630-0.755). The external validation showed significant correlations with the present model, with an AUC of 0.725 (95% CI 0.580-0.842). The comparison between our difficulty score and the previous grading system in the 272-patient cohort presented a significant difference in the AUC (0.701, 95% CI 0.643-0.755 vs. 0.644, 95% CI 0.584-0.701, P = 0.0452). CONCLUSION: The present difficulty scoring system, based on preoperative factors, has good performance in predicting the risk of intraoperative complications of LS and could be helpful for enabling appropriate case selection with respect to the current experience of a surgeon.

Single Large Nodule (>5 cm) Prognosis in Hepatocellular Carcinoma: Kinship with Barcelona Clinic Liver Cancer (BCLC) Stage A or B?

BACKGROUND The aim of the present study was to evaluate the prognosis among patients with a single large hepatocellular carcinoma (HCC) >5 cm compared with other patients in Barcelona Clinic Liver Cancer (BCLC) stage A or stage B. MATERIAL AND METHODS Data on patients with BCLC stage A/B HCC were collected between 2008 and 2012. BCLC stage A was subclassified as A1 (single tumor, 2-5 cm, or 2-3 nodules £3 cm), or A2 (single tumor >5 cm). Overall survival (OS) was evaluated and compared. RESULTS Among 1005 patients with HCC, 455 were stage A1, 188 were stage A2, and 362 were stage B. The OS of stage A2 patients was significantly worse than that of stage A1 patients (median survival, 30.6 vs. 43.2 months, p5 cm had a comparable survival with BCLC stage B. HCC >5 cm should therefore be classified as an intermediate stage.

Prognostic factors and clinical outcomes in adult primary gliosarcoma patients: a Surveillance, Epidemiology, and End Results (SEER) analysis from 2004 to 2015.

Objective: Gliosarcoma (GSC), a rare malignant brain tumor, is considered as a variant of isocitrate dehydrogenase 1 wild type (IDH1-WT) glioblastoma (GBM). This study aimed to retrospectively analyze the clinical characteristics of GSC and compare whether there are some differences of treatment strategies and outcomes between GSC and GBM patients through Surveillance, Epidemiology, and End Results (SEER) database.Patients and methods: The clinical data of adults diagnosed with primary GSC between 2004 and 2015 were queried from SEER database. The Kaplan-Meier curve and the Cox model were performed to analyze the relationships between clinical parameters and patients' prognosis. Similar analyses were conducted for all primary GBM patients of SEER.Results: In total, 527 GSC and 20,541 GBM patients with complete and valid clinical information were finally enrolled for further analysis. Compared with GBM, GSC owned a proclivity to temporal lobe rather than frontal lobe (p < 0.001), a less conservative extension of resection (EOR) (p < 0.001), and a higher sensitivity to radiotherapy (p < 0.001). As shown by univariate analysis, surgery, radiotherapy and chemotherapy could prolong the overall survival (OS) time of GSC, but EOR did not confer an advantage to the outcomes of patients, no matter whether combined radio/chemotherapy was given. In multivariate analysis, age more than 60 and lack of radio/chemotherapy were identified as independent risk factors for OS of GSC patients.Conclusions: Our study found that although EOR seemed to be important to GBM, the extent of surgery did not show a clear relationship with the improved prognosis of GSC. Additionally, radiotherapy and chemotherapy could prolong patients' survival time significantly, which suggests a more positive role of them in treating GSC and needs further investigations.

High-Protein Diet Induces Hyperuricemia in a New Animal Model for Studying Human Gout.

Hyperuricemia is a central risk factor for gout and increases the risk for other chronic diseases, including cardiometabolic disease, kidney disease, and hypertension. Overproduction of urate is one of the main reasons for hyperuricemia, and dietary factors including seafoods, meats, and drinking are contributed to the development of it. However, the lack of a suitable animal model for urate metabolism is one of the main reasons for the delay and limitations of hyperuricemia research. Combining evolutionary biological studies and clinical studies, we conclude that chicken is a preferred animal model for hyperuricemia. Thus, we provided chickens a high-protein diet (HPD) to evaluate the changes in the serum urate levels in chickens. In our study, the HPD increased the serum urate level and maintained it at a long-term high level in chickens. Long-term high serum urate levels induced an abnormal chicken claw morphology and the precipitation of monosodium urate (MSU) in joint synovial fluid. In addition, a long-term HPD also decreased the glomerular filtration rate and induced mild renal injury. Most importantly, allopurinol and probenecid displayed the positive effects in decreasing serum urate and then attenuated hyperuricemia in chicken model. These findings provide a novel model for hyperuricemia and a new opportunity to further investigate the effects of long-term hyperuricemia on other metabolic diseases.

[Apparent Diffusion Coefficient Histogram Analysis:Differentiation of Genetic Subtypes of Diffuse Lower-grade Gliomas].

Objective To explore the utility of apparent diffusion coefficient(ADC)histogram analysis for differentiating genetic subtypes of diffuse lower-grade gliomas. Methods A total of 55 patients with WHO grade Ⅱ/Ⅲ diffuse lower-grade gliomas who underwent preoperative routine brain magnetic resonance imaging and diffusion weighted imaging in our center were retrospectively evaluated.Among whom there were 14 patients with isocitrate dehydrogenase(IDH)wild-type gliomas(IDH wt group),19 patients with IDH-mutant 1p19q intact gliomas(IDH mut1p19q int group),and 22 patients with IDH-mutant 1p19q co-deleted gliomas(IDH mut1p19q del group).The whole-lesion ADC values derived from histogram analysis(including ADCmean,ADCminimum,ADC5%,ADC10%,ADC25%,ADC50%,ADC75%,ADC90%,ADC95%,ADCmaximum,mode,range,skewness,kurtosis,standard deviation,inhomogeneity,and entrophy)were measured for each patient.All parameters between the different genetic subtypes were compared by using the Student's t test or Mann-Whitney U test.Receiver operating curve(ROC)analysis was used to assess the diagnostic performance of ADC histogram in distinguishing the different genetic subtypes. Results Compared with IDH wt group,the ADC75%(P=0.021),ADC90%(P=0.015),ADC95%(P=0.014),ADCmaximum (P=0.035),range(P=0.009),standard deviation(P=0.001)and inhomogeneity(P=0.001)were significantly lower in IDH mut group;in contrast,the ADCminimum (P=0.031)and kurtosis(P=0.020)of IDH mut group were significantly higher than those in IDH wt group.The ADCmean(P=0.010),ADC5%(P=0.016),ADC10%(P=0.012),ADC25%(P=0.007),ADC50%(P=0.005),ADC75%(P=0.015),and mode(P=0.002)were significantly higher in IDH mut1p19q int group than in IDH mut1p19q del group.Inhomogeneity achieved the highest area under ROC(AUC)(0.811)in differentiating IDH mut gliomas and IDH wt gliomas,with a cutoff value of 0.229;the sensitivity and specificity were 85.7% and 73.2%.The mode achieved the highest AUC(0.744)in differentiating IDH mut1p19q int gliomas and IDH mut1p19q del gliomas,with a cutoff value was 1448.75×10 -6 mm 2/s;the sensitivity and specificity were 57.9% and 90.9%.Conclusion ADC histograms analysis may be helpful to differentiate genetic subtypes in lower-grade gliomas.

An emergent understanding of strand displacement in RNA biology.

DNA and RNA are generally regarded as central molecules in molecular biology. Recent advancements in the field of DNA/RNA nanotechnology successfully used DNA/RNA as programmable molecules to construct molecular machines and nanostructures with predefined shapes and functions. The key mechanism for dynamic control of the conformations of these DNA/RNA nanodevices is a reaction called strand displacement, in which one strand in a formed duplex is replaced by a third invading strand. While DNA/RNA strand displacement has mainly been used to de novo design molecular devices, we argue in this review that this reaction is also likely to play a key role in multiple cellular events such as gene recombination, CRISPR-based genome editing, and RNA cotranscriptional folding. We introduce the general mechanism of strand displacement reaction, give examples of its use in the construction of molecular machines, and finally review natural processes having characteristic which suggest that strand displacement is occurring.