Efficacy and safety of intracoronary pro-urokinase combined with low-pressure balloon pre-dilatation during percutaneous coronary intervention in patients with anterior ST-segment elevation myocardial infarction.

BACKGROUND: The efficacy and safety of low-pressure balloon pre-dilatation before intracoronary pro-urokinase (pro-UK) in preventing no-reflow during percutaneous coronary intervention (PCI) remains unknown. This study aimed to evaluate the clinical outcomes of intracoronary pro-UK combined with low-pressure balloon pre-dilatation in patients with anterior ST-segment-elevation myocardial infarction (STEMI). METHODS: This was a randomized, single-blind, investigator-initiated trial that included 179 patients diagnosed with acute anterior STEMI. All patients were eligible for PCI and were randomized into two groups: intracoronary pro-UK combined with (ICPpD group, n = 90) or without (ICP group, n = 89) low-pressure balloon pre-dilatation. The main efficacy endpoint was complete epicardial and myocardial reperfusion. The safety endpoints were major adverse cardiovascular events (MACEs), which were analyzed at 12 months follow-up. RESULTS: Patients in the ICPpD group presented significantly higher TIMI myocardial perfusion grade 3 (TMPG3) compared to those in the ICP group (77.78% versus 68.54%, P = 0.013), and STR ≥ 70% after PCI 30 min (34.44% versus 26.97%, P = 0.047) or after PCI 90 min (40.0% versus 31.46%, P = 0.044). MACEs occurred in 23 patients (25.56%) in the ICPpD group and in 32 patients (35.96%) in the ICP group. There was no difference in hemorrhagic complications during hospitalization between the groups. CONCLUSION: Patients with acute anterior STEMI presented more complete epicardial and myocardial reperfusion with adjunctive low-pressure balloon pre-dilatation before intracoronary pro-UK during PCI. TRIAL REGISTRATION: 2019xkj213.

Natural flavonols as probes for direct determination of borax: From conventional fluorescence analysis to paper-based smartphone sensing.

Borax is strictly regulated in the food processing and pharmaceutical industry due to its physiological toxicity, and the development of a direct analytical method is essential for effectively monitoring the borax abuse. In this work, the fluorescence properties of flavonoids, including flavones, isoflavones and flavonols, were systematically investigated from aqueous to borax solutions, and it was found that the weak intrinsic fluorescence of flavonols could be pervasively sensitized by borax. A natural flavonol, morin, was subsequently chosen as a representative probe to develop a turn-on fluorescence sensing method for borax analysis, which achieved a linear response spanning four orders of magnitude with a detection limit of 1.07 µM (0.22 µg mL-1 in terms of Na2B4O7 content). Furthermore, a smartphone-assisted paper-based test device was designed and constructed by 3D printing technology. Using morin-impregnated test strips as the carrier, the borax could be visually detected by the RGB signals of the captured images, with a detection limit of 0.13 mM (27.05 µg mL-1 for Na2B4O7). Combining ion exchange treatment for food samples and sodium periodate oxidation for drug samples, the developed methods were successfully applied for the direct analysis of borax in various products with the recoveries of 86.9-106.3% for traditional fluorescence analysis and 82.7-108.8% for smartphone-assisted fluorescence sensing. The fluorescence property of the morin-borax system was studied using time-dependent density functional theory, and the sensing mechanism was discussed in conjunction with experimental research.

Novel Evodiamine-Based Sulfonamide Derivatives as Potent Insecticide Candidates Targeting Insect Ryanodine Receptors.

Pests represent an important impediment to efficient agricultural production and pose a threat to global food security. On the basis of our prior research focused on identifying insecticidal leads targeting insect ryanodine receptors (RyRs), we aimed to identify evodiamine scaffold-based novel insecticides. Thus, a variety of evodiamine-based derivatives were designed, synthesized, and assessed for their insecticidal activity against the larvae of Mythimna separata (M. separata) and Plutella xylostella (P. xylostella). The preliminary bioassay results revealed that more than half of the target compounds exhibited superior activity compared to evodiamine, matrine, and rotenone against M. separata. Among these, compound 21m displayed the most potent larvicidal efficiency, with a remarkable mortality rate of 93.3% at 2.5 mg/L, a substantial improvement over evodiamine (10.0% at 10 mg/L), matrine (10.0% at 200 mg/L), and rotenone (30.0% at 200 mg/L). In the case of P. xylostella, compounds 21m and 21o displayed heightened larvicidal activity, boasting LC50 values of 9.37 × 10-2 and 0.13 mg/L, respectively, surpassing that of evodiamine (13.41 mg/L), matrine (291.78 mg/L), and rotenone (18.39 mg/L). A structure-activity relationship analysis unveiled that evodiamine-based derivatives featuring a cyclopropyl sulfonyl group at the nitrogen atom of the B ring and a fluorine atom in the E ring exhibited more potent larvicidal effects. This finding was substantiated by calcium imaging experiments and molecular docking, which suggested that 21m could target insect RyRs, including resistant mutant RyRs of P. xylostella (G4946E and I4790M), with higher affinity than chlorantraniliprole (CHL). Additionally, cytotoxicity assays highlighted that the potent compounds 21i, 21m, and 21o displayed favorable selectivity and low toxicity toward nontarget organisms. Consequently, compound 21m emerges as a promising candidate for further development as an insecticide targeting insect RyRs.

Recent Advances in Aptasensors for Rapid Pesticide Residues Detection.

Pesticides are applied widely to increase agricultural output and quality, however, this practice results in residual issues that not only harm the environment but also put people and animals' lives and health at risk. As a result, it is critical to find pesticide residues in a variety of sources, including crops, water supplies, and soil. Aptamers are more flexible in their synthesis and modification, have a high level of specificity, are inexpensive, and have good stability compared to conventional detection methods. They have therefore attracted a lot of interest in the industry. This study reviews the most recent aptasensor advancements in the detection of pesticide residues. Firstly, aptamers specifically binding to many pesticides are summarized. Secondly, the combination of aptasensors with colorimetric, fluorescent, surface enhanced Raman spectroscopy (SERS), resonance Light Scattering (RLS), chemiluminescence (CL), electrochemical, and electrochemiluminescence (ECL) technologies are systematically introduced, and their advantages and disadvantages are expounded. Importantly, the aptasensors for the detection of various pesticides (organochlorine, organophosphorus, neonicotinoids, carbamates, and pyrethroids) that have been developed so far are systematically analyzed and discussed. Finally, the furture prospects and challenges of the aptasensors are highlighted. It is expected to offer suggestions for the later creation of novel, highly effective and sensitive aptasensors for the detection of pesticide residues.

Smart Targeted Delivery Systems for Enhancing Antitumor Therapy of Active Ingredients in Traditional Chinese Medicine.

As a therapeutic tool inherited for thousands of years, traditional Chinese medicine (TCM) exhibits superiority in tumor therapy. The antitumor active components of TCM not only have multi-target treatment modes but can also synergistically interfere with tumor growth compared to traditional chemotherapeutics. However, most antitumor active components of TCM have the characteristics of poor solubility, high toxicity, and side effects, which are often limited in clinical application. In recent years, delivering the antitumor active components of TCM by nanosystems has been a promising field. The advantages of nano-delivery systems include improved water solubility, targeting efficiency, enhanced stability in vivo, and controlled release drugs, which can achieve higher drug-delivery efficiency and bioavailability. According to the method of drug loading on nanocarriers, nano-delivery systems can be categorized into two types, including physically encapsulated nanoplatforms and chemically coupled drug-delivery platforms. In this review, two nano-delivery approaches are considered, namely physical encapsulation and chemical coupling, both commonly used to deliver antitumor active components of TCM, and we summarized the advantages and limitations of different types of nano-delivery systems. Meanwhile, the clinical applications and potential toxicity of nano-delivery systems and the future development and challenges of these nano-delivery systems are also discussed, aiming to lay the foundation for the development and practical application of nano-delivery systems of TCM in clinical settings.

Intermittent energy restriction changes the regional homogeneity of the obese human brain.

Background: Intermittent energy restriction (IER) is an effective weight loss strategy. However, the accompanying changes in spontaneous neural activity are unclear, and the relationship among anthropometric measurements, biochemical indicators, and adipokines remains ambiguous. Methods: Thirty-five obese adults were recruited and received a 2-month IER intervention. Data were collected from anthropometric measurements, blood samples, and resting-state functional magnetic resonance imaging at four time points. The regional homogeneity (ReHo) method was used to explore the effects of the IER intervention. The relationships between the ReHo values of altered brain regions and changes in anthropometric measurements, biochemical indicators, and adipokines (leptin and adiponectin) were analyzed. Results: Results showed that IER significantly improved anthropometric measurements, biochemical indicators, and adipokine levels in the successful weight loss group. The IER intervention for weight loss was associated with a significant increase in ReHo in the bilateral lingual gyrus, left calcarine, and left postcentral gyrus and a significant decrease in the right middle temporal gyrus and right cerebellum (VIII). Follow-up analyses showed that the increase in ReHo values in the right LG had a significant positive correlation with a reduction in Three-factor Eating Questionnaire (TFEQ)-disinhibition and a significant negative correlation with an increase in TFEQ-cognitive control. Furthermore, the increase in ReHo values in the left calcarine had a significant positive correlation with the reduction in TFEQ-disinhibition. However, no significant difference in ReHo was observed in the failed weight loss group. Conclusion: Our study provides objective evidence that the IER intervention reshaped the ReHo of some brain regions in obese individuals, accompanied with improved anthropometric measurements, biochemical indicators, and adipokines. These results illustrated that the IER intervention for weight loss may act by decreasing the motivational drive to eat, reducing reward responses to food cues, and repairing damaged food-related self-control processes. These findings enhance our understanding of the neurobiological basis of IER for weight loss in obesity.

The design and straightforward synthesis of multifunctional DNA microgels for the improved targeted delivery of antitumor drugs.

Multifunctional drug delivery platforms represent ideal approaches to reliably targeting pharmacological agents of interest to the complex tumor microenvironment (TME), yet the complicated synthesis processes, high costs, and toxicities associated with these agents have hindered their clinical application to date. In this study, the properties of the TME are leveraged to develop a multifunctional pNAB/AS DNA microgel that is able to actively target tumors. This microgel is generated by a straightforward one-step free radical precipitation polymerization procedure, exhibiting extremely high drug encapsulation efficiency (∼90%), and is responsive to three environmental stimuli including temperature, reduction, and an acidic pH while showing minimal drug leakage under physiological conditions. Through a synergistic combination of appropriate size and aptamer recognition, this microgel is able to reliably facilitate intratumoral drug accumulation and nuclear drug delivery. Critically, pNAB/AS-Dox treatment is associated with specific antitumor activity in vitro and in vivo while retaining a good biosafety profile and causing lower levels of off-target toxicity as compared to free drug treatment. Together, these findings emphasize the potential value of this multifunctional pNAB/AS DNA microgel as a platform amenable to targeted drug delivery to the TME, providing a foundation for further efforts to readily develop multifunctional drug delivery systems.

A nomogram based on genotypic and clinicopathologic factors to predict the non-sentinel lymph node metastasis in Chinese women breast cancer patients.

Background: Sentinel lymph node biopsy (SLNB) is the standard treatment for breast cancer patients with clinically negative axilla. However, axillary lymph node dissection (ALND) is still the standard care for sentinel lymph node (SLN) positive patients. Clinical data reveals about 40-75% of patients without non-sentinel lymph node (NSLN) metastasis after ALND. Unnecessary ALND increases the risk of complications and detracts from quality of life. In this study, we expect to develop a nomogram based on genotypic and clinicopathologic factors to predict the risk of NSLN metastasis in SLN-positive Chinese women breast cancer patients. Methods: This retrospective study collected data from 1,879 women breast cancer patients enrolled from multiple centers. Genotypic features contain 96 single nucleotide polymorphisms (SNPs) associated with breast cancer susceptibility, therapy and prognosis. SNP genotyping was identified by the quantitative PCR detection platform. The genetic features were divided into two clusters by the mutational stability. The normalized polygenic risk score (PRS) was used to evaluate the combined effect of each SNP cluster. Recursive feature elimination (RFE) based on linear discriminant analysis (LDA) was adopted to select the most useful predictive features, and RFE based on support vector machine (SVM) was used to reduce the number of SNPs. Multivariable logistic regression models (i.e., nomogram) were built for predicting NSLN metastasis. The predictive abilities of three types of model (based on only clinicopathologic information, the integrated clinicopathologic and all SNPs information, and integrated clinicopathologic and significant SNPs information) were compared. Internal and external validations were performed and the area under ROC curves (AUCs) as well as a series of evaluation indicators were assessed. Results: 229 patients underwent SLNB followed by ALND and without any neo-adjuvant therapy, 79 among them (34%) had a positive axillary NSLN metastasis. The LDA-RFE identified the characteristics including lymphovascular invasion, number of positive SLNs, number of negative SLNs and two SNP clusters as significant predictors of NSLN metastasis. Furthermore, the SVM-RFE selected 29 significant SNPs in the prediction of NSLN metastasis. In internal validation, the median AUCs of the clinical and all SNPs combining model, the clinical and 29 significant SNPs combining model, and the clinical model were 0.837, 0.795 and 0.708 respectively. Meanwhile, in external validation, the AUCs of the three models were 0.817, 0.815 and 0.745 respectively. Conclusion: We present a new nomogram by combining genotypic and clinicopathologic factors to achieve higher sensitivity and specificity comparing with traditional clinicopathologic factors to predict NSLN metastasis in Chinese women breast cancer. It is recommended that more validations are required in prospective studies among different patient populations.

Dual-drug codelivery nanosystems: An emerging approach for overcoming cancer multidrug resistance.

Multidrug resistance (MDR) promotes tumor recurrence and metastasis and heavily reduces anticancer efficiency, which has become a primary reason for the failure of clinical chemotherapy. The mechanisms of MDR are so complex that conventional chemotherapy usually fails to achieve an ideal therapeutic effect and even accelerates the occurrence of MDR. In contrast, the combination of chemotherapy with dual-drug has significant advantages in tumor therapy. A novel dual-drug codelivery nanosystem, which combines dual-drug administration with nanotechnology, can overcome the application limitation of free drugs. Both the characteristics of nanoparticles and the synergistic effect of dual drugs contribute to circumventing various drug-resistant mechanisms in tumor cells. Therefore, developing dual-drug codelivery nanosystems with different multidrug-resistant mechanisms has an important reference value for reversing MDR and enhancing the clinical antitumor effect. In this review, the advantages, principles, and common codelivery nanocarriers in the application of dual-drug codelivery systems are summarized. The molecular mechanisms of MDR and the dual-drug codelivery nanosystems designed based on different mechanisms are mainly introduced. Meanwhile, the development prospects and challenges of codelivery nanosystems are also discussed, which provide guidelines to exploit optimized combined chemotherapy strategies in the future.

Dynamical alterations of brain function and gut microbiome in weight loss.

Objective: Intermittent energy restriction (IER) is an effective weight loss strategy. However, little is known about the dynamic effects of IER on the brain-gut-microbiome axis. Methods: In this study, a total of 25 obese individuals successfully lost weight after a 2-month IER intervention. FMRI was used to determine the activity of brain regions. Metagenomic sequencing was performed to identify differentially abundant gut microbes and pathways in from fecal samples. Results: Our results showed that IER longitudinally reduced the activity of obese-related brain regions at different timepoints, including the inferior frontal orbital gyrus in the cognitive control circuit, the putamen in the emotion and learning circuit, and the anterior cingulate cortex in the sensory circuit. IER longitudinally reduced E. coli abundance across multiple timepoints while elevating the abundance of obesity-related Faecalibacterium prausnitzii, Parabacteroides distasonis, and Bacterokles uniformis. Correlation analysis revealed longitudinally correlations between gut bacteria abundance alterations and brain activity changes. Conclusions: There was dynamical alteration of BGM axis (the communication of E. coli with specific brain regions) during the weight loss under the IER.

Current perspectives and trend of nanomedicine in cancer: A review and bibliometric analysis.

The limitations of traditional cancer treatments are driving the creation and development of new nanomedicines. At present, with the rapid increase of research on nanomedicine in the field of cancer, there is a lack of intuitive analysis of the development trend, main authors and research hotspots of nanomedicine in the field of cancer, as well as detailed elaboration of possible research hotspots. In this review, data collected from the Web of Science Core Collection database between January 1st, 2000, and December 31st, 2021, were subjected to a bibliometric analysis. The co-authorship, co-citation, and co-occurrence of countries, institutions, authors, literature, and keywords in this subject were examined using VOSviewer, Citespace, and a well-known online bibliometrics platform. We collected 19,654 published papers, China produced the most publications (36.654%, 7204), followed by the United States (29.594%, 5777), and India (7.780%, 1529). An interesting fact is that, despite China having more publications than the United States, the United States still dominates this field, having the highest H-index and the most citations. Acs Nano, Nano Letters, and Biomaterials are the top three academic publications that publish articles on nanomedicine for cancer out of a total of 7580 academic journals. The most significant increases were shown for the keywords "cancer nanomedicine", "tumor microenvironment", "nanoparticles", "prodrug", "targeted nanomedicine", "combination", and "cancer immunotherapy" indicating the promising area of research. Meanwhile, the development prospects and challenges of nanomedicine in cancer are also discussed and provided some solutions to the major obstacles.

Bioactivity-Guided Synthesis Accelerates the Discovery of Evodiamine Derivatives as Potent Insecticide Candidates.

Pests threaten worldwide food security by decreasing crop yields and damaging their quality. Natural product-based molecular design and structural optimization have been one of the most effective ways to innovate pesticides for integrated insect management. To continue our previous studies on the discovery of insecticidal lead, a series of evodiamine derivatives were designed, synthesized, and evaluated for their insecticidal activities. The bioassay results demonstrated that compounds Ian and Iao exhibited 90 and 80% insecticidal activities against Mythimna separata at 2.5 mg/L, respectively, which were superior to evodiamine (10% at 10 mg/L), matrine (45% at 600 mg/L), and rotenone (30% at 200 mg/L). Compounds Ian-Iap showed 90% insecticidal activities against Plutella xylostella at 1.0 mg/L, far more potent than those of evodiamine, matrine, and rotenone. Compound Ian displayed 60% insecticidal activity against Helicoverpa armigera at 5.0 mg/L, while evodiamine, matrine, and rotenone showed very poor activities. The study on the insecticidal mechanism of action by a calcium imaging experiment indicated that the insect ryanodine receptors (RyRs) could be the potential target of Ian. Furthermore, the molecular docking indicated that Ian anchored in the binding site of the RyR of P. xylostella. The above results manifested the potential of evodiamine derivatives as potent insecticide candidates.

Discovery of evodiamine derivatives as potent insecticide candidates.

In the search for novel more effective insecticides, natural products could be used as ideal template compounds due to their good environmental compatibility, various bioactivities, unique scaffolds and mode of action. We have found that natural product evodiamine, the main active component from the fruits of Evodia rutaecarpa (Juss.) Benth, displayed obvious insecticidal activities against lepidoptera pests. To continue our research, a series of evodiamine derivatives 3a-3aa were rationally designed and synthesized. The larvicidal activities results indicated that most of target compounds displayed better efficacy than evodiamine, matrine, and rotenone against Mythimna separata, Plutella xylostella and Helicoverpa armigera, among which 3z exhibited excellent larvicidal activities (65% at 2.5 mg/L against M. separata, 75% at 1.0 mg/L against P. xylostella, and 85% 10 mg/L against H. armigera, respectively), much better than evodiamine (0%), matrine (0%), and rotenone (0%). The preliminary structure activity relationships demonstrated that the fluorine atom at the E ring of evodiamine had a positive influence on the larvicidal activity. The calcium imaging experiment studies indicated that 3z could act on the ryanodine receptor (RyR) of M. separata and was an effective calcium activator for RyR.

A Reverse Transcription Recombinase-Aided Amplification Method for Rapid and Point-of-Care Detection of SARS-CoV-2, including Variants.

The worldwide pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its emergence of variants needs rapid and point-of-care testing methods for a broad diagnosis. The regular RT-qPCR is time-consuming and limited in central laboratories, so a broad and large-scale screening requirement calls for rapid and in situ methods. In this regard, a reverse transcription recombinase-aided amplification (RT-RAA) is proposed here for the rapid and point-of-care detection of SARS-CoV-2. A set of highly conserved primers and probes targeting more than 98% of SARS-CoV-2 strains, including currently circulating variants (four variants of concerns (VOCs) and three variants of interest (VOIs)), was used in this study. With the preferred primers, the RT-RAA assay showed a 100% specificity to SARS-CoV-2 from eight other respiratory RNA viruses. Moreover, the assay here is of a high sensitivity and 0.48 copies/µL can be detected within 25 min at a constant temperature (42 °C), which can be realized on portable equipment. Furthermore, the RT-RAA assay demonstrated its high agreement for the detection of SARS-CoV-2 in clinical specimens compared with RT-qPCR. The rapid, simple and point-of-care RT-RAA method is expected to be an appealing detection tool to detect SARS-CoV-2, including variants, in clinical diagnostic applications.

Supercontinuum generation of 314.7 W ranging from 390 to 2400 nm by tapered photonic crystal fiber.

To consider both high-power handling and blue-extended supercontinuum (SC) generation, a long-tapered photonic crystal fiber is pumped by a high-power laser source. An SC ranging from 390 to 2400 nm with 314.7 W output power is obtained. A spectral component below 960 nm accounts for 36.1% of the total output power, exceeding 113.5 W, with a spectral flatness within 16 dB. To the best of our knowledge, this is the first time an SC coverage of all visible wavelengths with more than 300 W output power has been achieved. This result increases the output power of the SC covering the visible range by a factor of three.

Target-triggered entropy-driven amplification system-templated silver nanoclusters for multiplexed microRNA analysis.

MicroRNAs (miRNAs) are important biomarkers for the diagnosis, prognosis, and treatment of human diseases. Sensitive and selective detection of multiple miRNAs simultaneously will greatly facilitate the early and accurate diagnosis of cancers. Herein, a novel entropy-driven amplification system-templated silver nanoclusters sensing platform was developed for the multiplexed analysis of tumor-associated miRNAs. The sensing platform was constructed by coupling target-triggered entropy-driven catalysis with luminescence adjustable DNA-templated silver nanoclusters (Ag NCs). In the presence of target miRNA, the sensing platform initiates the branch migration and strand displacement of the complex, which has a six-base cytosine loop for stabilizing the luminous Ag NCs. The target is cyclically generated for new catalysis while turning off the fluorescence of Ag NCs; this is accompanied by a significantly amplified optical readout. In this study, two different complex-stabilized Ag NCs systems were proposed, the yellow-emitting Ag NCs and red-emitting Ag NCs biosensors enabled the analysis of miRNA-141 and miRNA-155 with detection limits of 6.1 pM and 8.7 pM, respectively. Impressively, owing to the excellent selectivity, flexibility, and narrow-band excitation of the platform, the multiplexed synchronous detection of miRNA-141 and miRNA-155 were achieved in buffer, biological cell lysates and human serum samples with satisfactory results. The simple, flexible, and convenient strategy provides a powerful tool for multiple biomarkers analysis and related clinical applications.

Discovery of a polysubstituted phenyl containing novel N-phenylpyrazole scaffold as potent ryanodine receptor activator.

To develop the novel ryanodine receptors (RyRs) insecticides, encouraged by our previous research work, a series of novel N-phenylpyrazole derivatives containing a polysubstituted phenyl ring scaffold were designed and synthesized. The bioassays results indicated that some title compounds exhibited excellent insecticidal activity. For oriental armyworm (Mythimna separata), compounds 7f, 7g, 7i and 7o at 0.5 mg L-1 displayed 100% larvicidal activity, and even at 0.1 mg L-1, 7o was 30% larvicidal activity, comparable to chlorantraniliprole (30%) and better than cyantraniliprole (10%). Compounds 7f and 7o had the median lethal concentrations (LC50) of 8.83 × 10-2 and 7.12 × 10-2 mg L-1, respectively, close to chlorantraniliprole (6.79 × 10-2 mg L-1). Additionally, for diamondback moth (Plutella xylostella), the larvicidal activity of compounds 7f and 7i were 90% and 70% at 0.01 mg L-1, respectively, better than chlorantraniliprole (50%) and cyantraniliprole (40%). More impressively, the LC50 value of 7f was 4.2 × 10-3 mg L-1, slightly lower than that of chlorantraniliprole (5.0 × 10-3 mg L-1). The molecular docking between compound 7f and RyRs of diamondback moth validated our molecular designation. Furthermore, the calcium imaging experiment explored the influence of compound 7o on the calcium homeostasis in the central neurons of the third larvae of oriental armyworm. The results of this study indicated that 7o is a potent novel lead targeting at RyRs.

Sensitive homogeneous fluorescent detection of DNA glycosylase by target-triggering ligation-dependent tricyclic cascade amplification.

Abnormal DNA glycosylases are concerned with the aging process as well as numerous pathologies in humans. Herein, a sensitive fluorescence method utilizing target-induced ligation-dependent tricyclic cascade amplification reaction was developed for the detecting DNA glycosylase activity. The presence of DNA glycosylase triggered the cleavage of damaged base in hairpin substrate, successively activating ligation-dependent strand displacement amplification (SDA) and exponential amplification reaction (EXPAR) for the generation of large amount of reporter probes. The resultant reporter probes bound with the signal probes to form stable dsDNA duplexes. And then the signal probes could be digested circularly in the dsDNA duplexes by T7 exonuclease, leading to the generation of an enhanced fluorescence signal. Due to the high efficiency of tricyclic cascade amplification and the low background signal deriving from the inhibition of nonspecific amplification, this method exhibited a detection limit of 0.14 U/mL and a dynamic range from 0.16 to 8.0 U/mL. Moreover, it could be applied for detecting DNA glycosylase activity in human serum with good selectivity and high sensitivity, and even quantifying other types of enzyme with 5'-PO4 residue cleavage product by rationally designing the corresponding substrate. Importantly, this method could be performed in homogenous solution without any complicated separation steps, providing a new strategy for DNA glycosylase-related biomedical research.

Clinical efficacy of the partial rectus muscle transportation procedure for paralytic strabismus.

AIM: To analyze the clinical efficacy of the partial rectus muscle transportation (PRT) procedure for paralytic strabismus due to single rectus muscle palsy. METHODS: In total, 28 patients (31 eyes) who underwent the PRT procedure for paralytic strabismus due to single rectus muscle palsy were retrospectively examined. The following data were collected pre- and postoperatively: angle of deviation in the primary position, presence of diplopia in the primary position, presence of compensatory head posture, and motility of the affected eye. The follow-up period was 6mo. RESULTS: Based on the preoperative and intraoperative findings, different operations were performed: 2 eyes were treated with PRT, 26 eyes were treated with PRT combined with the recession of the antagonist muscle (Am) of the paralytic rectus muscle, and 3 eyes were treated with PRT along with the recession of the Am and the yoke muscle (Ym). On the first day after the operation, 24 patients were found to be orthophoric in the primary position, without diplopia or abnormal head posture. Moreover, 2 patients with monocular lateral rectus muscle palsy had mild overcorrection to 5 prism diopters (PD) and 8 PD, respectively, whereas 2 patients with binocular lateral rectus muscle palsy had mild undercorrection to 8 PD and 10 PD, respectively. During the 6-month follow-up period, the mean deviation was rectified from 96.79±41.21 PD to 0.64±2.38 PD (t=12.48, P<0.001), whereas the deviations in the 2 patients with mild overcorrection were corrected to orthotropia. The mean preoperative limitation of motility improved from -4.55±0.51 to -2.65±0.61 (t=-15.13, P<0.001) after 6mo postoperatively. CONCLUSION: PRT is an effective treatment for complete paralytic strabismus due to single rectus muscle palsy, and can achieve stable clinical efficacy.

Electric Field-Driven On-Request Instant in Situ Formation/Removal of Solid Hydrogel within Microchannels for Efficient Electrophoretic Separation.

Electrophoretic separation in short microchannels is a promising way for rapid analysis of biomolecules, but the pressurized laminar flow may compromise the separation efficiency. In this work, through an electric field, instant formation and removal of a solid chitosan/ß-glycerol phosphate (CS/ß-GP) hydrogel within microchannels of microchips were realized. In a typical cross-type microchip, the CS/ß-GP hydrogel was precisely formed in the separation microchannel within 15 s of the application of a voltage of 2000 V. Highly efficient separation of peptides and proteins was achieved, and theoretical plate numbers of 0.6 to 1.5 × 106/m were attained for proteins in 120 s. The used hydrogel could be swiftly removed also with an electric field, and the whole procedure was achieved on a standard microchip electrophoresis device with no extra accessory or special operation required.