Spectral Characteristics and Displacement Sensing of U-Shaped Single-Mode-Multimode-Single-Mode Fiber Structure.

The U-shaped fiber configuration represents the elementary form of micro-displacement sensing, characterized by its exceptional freedom and flexibility. The study proposes the U-shaped bent single-mode-multimode-single-mode (SMS) fiber structure that integrates the multimode interference (MMI) effect for enhanced mode dispersion and the Mach-Zönder interference (MZI) effect for spectral sensitivity improvement. The transmission spectral properties of the U-shaped SMS fiber structure with a bent radius over 1 cm are experimentally measured as the change in displacement varied within the range of 5 mm in this work. As the radius decreases, the spectrum shows redshift, which is related to the central wavelength of the peak or dips-a smaller wavelength results in a stronger redshift for the same displacement change. The average sensitivity of micro-displacement measurement within a range of 5 mm is 5.41 pm/µm, and the linearity is 99.62%. The maximum sensitivity of U-shaped SMS fiber structure is 34.46 pm/µm, with the minimum displacement change of approximately 5.804 nm. The transmission spectral properties of the U-shaped SMS fiber structure within the ranges of 50 µm, 500 µm, and 5 mm are experimentally measured in this work. This experiment observed a relatively uniform spectral drift pattern in a large range of micro-displacement sensing. The measurement range is limited by the limited spectral range of the light source and the discontinuous variation in the effective refractive index. This provides an experimental reference for further understanding the characteristics of U-shaped fiber structures and applying its application in micro-displacement sensing.

Unveiling the genetic architecture and transmission dynamics of a novel multidrug-resistant plasmid harboring blaNDM-5 in E. Coli ST167: implications for antibiotic resistance management.

BACKGROUND: The emergence of multidrug-resistant (MDR) Escherichia coli strains poses significant challenges in clinical settings, particularly when these strains harbor New Delhi metallo-ß-lactamase (NDM) gene, which confer resistance to carbapenems, a critical class of last-resort antibiotics. This study investigates the genetic characteristics and implications of a novel blaNDM-5-carrying plasmid pNDM-5-0083 isolated from an E. coli strain GZ04-0083 from clinical specimen in Zhongshan, China. RESULTS: Phenotypic and genotypic evaluations confirmed that the E. coli ST167 strain GZ04-0083 is a multidrug-resistant organism, showing resistance to diverse classes of antibiotics including ß-lactams, carbapenems, fluoroquinolones, aminoglycosides, and sulfonamides, while maintaining susceptibility to monobactams. Investigations involving S1 pulsed-field gel electrophoresis, Southern blot analysis, and conjugation experiments, alongside genomic sequencing, confirmed the presence of the blaNDM-5 gene within a 146-kb IncFIB plasmid pNDM-5-0083. This evidence underscores a significant risk for the horizontal transfer of resistance genes among bacterial populations. Detailed annotations of genetic elements-such as resistance genes, transposons, and insertion sequences-and comparative BLAST analyses with other blaNDM-5-carrying plasmids, revealed a unique architectural configuration in the pNDM-5-0083. The MDR region of this plasmid shares a conserved gene arrangement (repA-IS15DIV-blaNDM-5-bleMBL-IS91-suI2-aadA2-dfrA12) with three previously reported plasmids, indicating a potential for dynamic genetic recombination and evolution within the MDR region. Additionally, the integration of virulence factors, including the iro and sit gene clusters and enolase, into its genetic architecture poses further therapeutic challenges by enhancing the strain's pathogenicity through improved host tissue colonization, immune evasion, and increased infection severity. CONCLUSIONS: The detailed identification and characterization of pNDM-5-0083 enhance our understanding of the mechanisms facilitating the spread of carbapenem resistance. This study illuminates the intricate interplay among various genetic elements within the novel blaNDM-5-carrying plasmid, which are crucial for the stability and mobility of resistance genes across bacterial populations. These insights highlight the urgent need for ongoing surveillance and the development of effective strategies to curb the proliferation of antibiotic resistance.

Efficacy and safety of robotic radical hysterectomy in cervical cancer compared with laparoscopic radical hysterectomy: a meta-analysis.

Introduction: Robotic radical hysterectomy (RRH) is a newly developed minimally invasive surgery that has been suggested as a substitute for laparoscopic radical hysterectomy (LRH). This meta-analysis aims to assess the clinical efficacy and safety of robot-assisted radical hysterectomy (RRH) for cervical cancer. Materials and methods: A systematic search was conducted in four databases (Medline, Embase, Web of Science, and CENTRAL) for studies comparing the utilization of RRH and LRH in the treatment of cervical cancer. The search included articles published from the inception of the databases up until July 18, 2023. Meta-analyses were conducted to assess several surgical outcomes, including operation time, estimated blood loss, length of hospital stay, pelvic lymph nodes, positive surgical margin, total complications, one-year recurrence rate, one-year mortality, and one-year disease-free survival rate. Results: Six studies were included for meta-analysis. In total, 234 patients were in the RRH group and 174 patients were in the LRH group. RRH had significantly longer operative time (MD=14.23,95% CI:5.27~23.20, P=0.002),shorter hospital stay (MD= -1.10,95% CI:-1.43~0.76, P <0.00001),more dissected pelvic lymph nodes(MD=0.89,95%CI:0.18~1.60, P =0.01) and less blood loss(WMD = -27.78,95%CI:-58.69 ~ -3.14, P=0.08, I2 = 80%) compared with LRH. No significant difference was observed between two groups regarding positive surgical margin (OR = 0.59, 95% CI 0.18~2.76, P=0.61), over complications (OR = 0.77, 95% CI, 0.46-1.28, P=0.31), one-year recurrence rate (OR = 0.19, 95% CI 0.03-1.15, P=0.13), one-year mortality rate (OR = 0.19, 95% CI 0.03-1.15, P=0.07) and disease-free survival at one year (OR = 1.92, 95% CI 0.32-11.50, P=0.48). Conclusion: RRH is an increasingly popular surgical method known for its high level of security and efficiency. It has many benefits in comparison to LRH, such as decreased blood loss, a higher quantity of dissected pelvic lymph nodes, and a shorter duration of hospitalization. Further multicenter, randomized controlled trials with extended follow-up durations are necessary to conclusively determine the safety and efficacy of RRH, as no significant differences were observed in terms of positive surgical margin, postoperative complications, 1-year recurrence, 1-year mortality, and 1-year disease-free survival. Systematic Review Registration: PROSPERO, identifier CRD42023446653.

The Incidence of Metabolic Syndrome in People Over 40 Years Old with Normal Fasting Plasma Glucose and the Predictive Cutoff Value of Effective Fasting Plasma Glucose for Metabolic Syndrome in Guiyang.

Purpose: This study aimed to investigate the incidence of metabolic syndrome (MS) in people over 40 years of age with normal blood glucose levels in Guiyang's urban areas and determine the effective glycemic cutoff value for predicting MS. Methods: The analysis was based on anthropometric and biochemical indicators of residents aged 40 years or older in urban areas of Guiyang City who participated in the "Epidemiological Study of Tumor Risk in Chinese Patients with Type 2 Diabetes" in 2011. This study included 3509 patients (2567 females and 942 males) with normal fasting plasma glucose (FPG) and no MS. Multivariate logistic regression was used to analyze the correlation between FPG and MS ROC was used to analyze the effective cutoff value of FPG for the incidence of MS. Results: After 3-year follow-up, 675 patients had MS (567 females and 108 males). MS incidence in the total population was 19.24%, 11.46% in males, and 22.09% in females, and it increased with FPG. After multivariate logistic regression analysis, the risk of MS corresponding to FPG in females and males was OR=4.607,95% CI (3.477-6.105) and OR=2.944, 95% CI (1.785-4.855), respectively. ROC results demonstrated that FPG could predict the onset of MS (AUC: 0.720 in males and 0.666 in females). Conclusion: Increased FPG correlated with the incidence of metabolic syndrome. Subjects with FPG in the normal range still had a high incidence of MS. The population cutoff value for predicting effective FPG for metabolic syndrome was 5.545 mmol/L in men and 5.605 mmol/L in women. Epidemiological investigations are needed to determine whether a lower FPG cutoff value is required to diagnose MS. FPG not only diagnoses diabetes but also serves as a cost-effective and convenient screening method for developing of MS in the general Chinese population.

Enzyme-Assisted Amplification and Copper Nanocluster Fluorescence Signal-Based Method for miRNA-122 Detection.

At present, a large number of studies have demonstrated that miRNAs can be used as biological indicators for the diagnosis and treatment of diseases such as tumours and cancer, so it is important to develop a new miRNA detection platform. In this work, miRNA-122 is used as the basis for targeting detection agents. We have designed an unlabelled DNA1 that undergoes partial hybridisation and has a 20 T base long strand. The fluorescent signal in this experiment is derived from copper nanoclusters (CuNCs) generated on the circular T-long strand of DNA1. At the same time, DNA1 is able to react with miRNA-122 and achieve hydrolysis of the part bound to miRNA-122 via the action of nucleic acid exonuclease III (Exo III), leaving a part of the DNA, called DNA3, while releasing miRNA-122 to participate in the next reaction, thus achieving circular amplification. DNA3 is able to react with DNA2, which is bound to streptavidin magnetic beads (SIBs) and separated from the reaction solution via the application of a magnetic field. Overall, this is a fluorescence signal reduction experiment, and the strength of the fluorescence signal from the copper nanoclusters can determine whether the target miRNA-122 is present or not. The degree of fluorescence reduction indicates how much DNA1, and thus the amount of target miRNA-122, has been hydrolysed. By evaluating the variations in the fluorescence signal under optimised conditions, we discovered that this method has good sensitivity, with a detection limit as low as 0.46 nM, better than many other previous works on fluorescence signal-based biosensors for miRNA detection. This technique offers high discrimination and selectivity and can serve as a persuasive reference for early diagnosis.

Electrochemical DNA Biosensors with Dual-Signal Amplification Strategy for Highly Sensitive HPV 16 Detection.

Cervical cancer is an important topic in the study of global health issues, ranking fourth among women's cancer cases in the world. It is one of the nine major cancers that China is focusing on preventing and treating, and it is the only cancer that can be prevented through vaccination. Systematic and effective screening for human papilloma (HPV) infection, which is closely linked to the development of cervical cancer, can reduce cervical cancer incidence and mortality. In this paper, an electrochemical sensor was designed to detect HPV 16 using dual-signal amplification. An APTES-modified glassy carbon electrode was used for improved stability. Gold nanoparticles and a chain amplification reaction were combined for signal amplification. The limit of detection (LOD) of this electrochemical sensor was 1.731 × 10-16 mol/L, and the linear response of the target detector range was from 1.0 × 10-13 mol/L to 1.0 × 10-5 mol/L (R2 = 0.99232). The test of serum sample recovery showed that it has good anti-interference, and the performance of all aspects was improved to different degrees compared with the previous research from the team. The designed sensor is centered around the principles of low cost, high sensitivity and stability, which provides new ideas for the future development of cervical cancer prevention and electrochemical biosensors.

Paper-based microfluidics and tailored gold nanoparticles for visual colorimetric detection of multiplex allergens.

The highly efficient and accurate recognition of targeted allergens is an essential element in the diagnosis of allergic diseases and follow-up desensitization treatment in clinic. The current clinical methods widely used to detect sIgE are high cost, time-consuming procedures, and bulky equipment. Herein, a multiplex microfluidic paper-based device (multi-µPAD) was developed that combined with tailored gold nanoparticles for simultaneously visual, colorimetric detection of different allergens in serum. This device could be used as quantitative detection of sIgE with LOD as low as 0.246 KUA/L in colorimetric method. In vitro results also showed that this device possessed good repeatability, high accuracy and incredible stability in different pH (6.0-7.4) and temperature (24-37 °C), as well as long-term storage within 90-day. Finally, this method was successfully utilized for assessing clinical multi-sample screening in 35 allergic patients. After the addition of the samples from allergic patients, the agreement rate of clinical results with commercial enzyme-linked immunosorbent assay (ELISA) kit reached more than 97%, which further indicated that this device had the advantages of efficient, accurate and sensitive to screen various allergens in real clinical serum samples. Therefore, by simply altering antigens and antibodies, this device can also be used for high-throughput detection of other allergens, making it considerable potential for clinical diagnosis of allergic diseases.

A novel risk model based on white blood cell-related biomarkers for acute kidney injury prediction in patients with ischemic stroke admitted to the intensive care unit.

Background: Conventional systemic inflammatory biomarkers could predict prognosis in patients with ischemic stroke (IS) admitted to the intensive care unit (ICU). Acute kidney injury (AKI) is common in patients with IS admitted to ICU, but few studies have used systemic inflammatory biomarkers to predict AKI in critically ill patients with IS. This study aimed to establish a risk model based on white blood cell (WBC)-related biomarkers to predict AKI in critically ill patients with IS. Methods: Data were extracted from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) for a training cohort, and data were extracted from the Medical Information Mart for eICU Collaborative Research Database (eICU-CRD) for a validation cohort. Logistic regression analysis was used to determine the significant predictors of WBC-related biomarkers on AKI prediction, and a risk model was established based on those significant indicators in multivariate logistic regression. The receiver operating characteristics (ROC) curve was utilized to obtain the best cut-off value of the risk model. The Kaplan-Meier curve was used to evaluate the prognosis-predictive ability of the risk model. Results: The overall incidence of AKI was 28.4% in the training cohort and 33.2% in the validation cohort. WBC to lymphocyte ratio (WLR), WBC to basophils ratio (WBR), WBC to hemoglobin ratio (WHR), and neutrophil to lymphocyte ratio (NLR) could independently predict AKI, and a novel risk model was established based on WLR, WBR, WHR, and NLR. This risk model depicted good prediction performance both in AKI and other clinical outcomes including hemorrhage, persistent AKI, AKI progression, ICU mortality, and in-hospital mortality both in the training set and in the validation set. Conclusion: A risk model based on WBC-related indicators exhibited good AKI prediction performance in critically ill patients with IS which could provide a risk stratification tool for clinicians in the ICU.

Gold Nanoparticle-Based Enzyme-Assisted Cyclic Amplification for the Highly-Sensitive Detection of miRNA-21.

Because microRNAs (miRNAs) are biological indicators for the diagnosis, treatment, and monitoring of tumors, cancers, and other diseases, it is significant to develop a rapid, sensitive, and reliable miRNA detection platform. In this study, based on miRNA-21 detection, DNA-a with a 3' end overhang and Texas Red fluorophore-labeled 5' end was designed, which reacts with miRNA-21 and hybridizes with exonuclease III (Exo III), where the part connected to miRNA-21 is hydrolyzed, leaving a-DNA. At the same time, miRNA-21 is released to participate in the following reaction, to achieve cyclic amplification. a-DNA reacts with DNA-b conjugated to gold nanoparticles to achieve fluorescence quenching, with the quenching value denoted as F; additionally, after adding DNA-d and linked streptavidin immunomagnetic beads (SIBs), fluorescence recovery was achieved using DNA-c, with the recovered fluorescence recorded as F0. By comparing the difference in the fluorescence (F0 - F) between the two experiments, the amount of DNA-a hydrolyzed to produce a-DNA was established to determine the target miRNA-21 content. Under optimized conditions, by comparing the changes in the fluorescence signal, the developed strategy shows good sensitivity and repeatability, with a detection limit of 18 pM, good discriminative ability and selectivity, and promise for the early diagnosis of breast and intestinal cancers.

APTES-Modified Remote Self-Assembled DNA-Based Electrochemical Biosensor for Human Papillomavirus DNA Detection.

High-risk human papillomavirus (HPV) infection is an important cause of cervical cancer formation; therefore, being able to detect high-risk HPV (e.g., HPV-16) is important for the early treatment and prevention of cervical cancer. In this study, a combination of a 3-aminopropyltriethoxysilane (APTES) modified gold electrode and a super sandwich structure was creatively developed, resulting in the development of a biosensor that is both sensitive and stable for the detection of HPV-16. The electrochemical biosensor possesses a lower detection limit compared with previous studies with an LOD of 5.475 × 10-16 mol/L and it possesses a wide linear range from 1.0 × 10-13 mol/L to 1.0 × 10-6 mol/L (R2 = 0.9923) for the target DNA. The experimental data show that the sensor has good stability, and there is no significant decrease in the current response value after 7 days in the low-temperature environment. In addition, the sensor proved to be a powerful clinical tool for disease diagnosis because it showed good interference resistance in complex human serum samples.

Peroxisome Proliferator-Activated Receptor Gene Knockout Promotes Podocyte Injury in Diabetic Mice.

Objective: To investigate the effects of peroxisome proliferator-activated receptor (PPARγ) expression on renal podocyte in diabetic mice by conditionally knockout mouse PPARγ gene. Methods: Wild-type C57BL mice and PPARγ gene knockout mice were used as research objects to establish the diabetic mouse model, which was divided into normal control group (NC group), normal glucose PPARγ gene knockout group (NK group), diabetic wild-type group (DM group), and diabetic PPARγ gene knockout group (DK group), with 8 mice in each group. After 16 weeks, the mice were sacrificed for renal tissue collection. Morphological changes of renal tissue were observed by HE and Masson staining, and ultrastructure of renal tissue was observed by transmission electron microscope. Protein expressions of PPARγ, podocin, nephrin, collagen IV, and fibronectin (FN) in renal tissues were detected by immunohistochemistry and Western blot, and mRNA changes of PPARγ, podocin, and nephrin in renal tissues were detected by qRT-PCR. Results: Compared with the NC group, the protein and mRNA expressions of PPARγ, podocin, and nephrin decreased in the kidney tissue of mice in the DM group, while the protein expressions of collagen IV and FN increased. The expression of various proteins in kidney tissues of the DK group was consistent with that of the DM group, and the difference was more obvious. The expression of PPARγ protein and mRNA decreased in the NK group, while the expression of podocin, nephrin protein and mRNA, collagen IV, and FN protein showed no significant difference. Conclusion: In diabetic renal tissue, the loss of PPARγ can aggravate podocellular damage and thus promote the occurrence of diabetic renal fibrosis. Increasing the expression of PPARγ may effectively relieve renal podocyte impairment in diabetic patients, which can be used for the treatment of diabetic nephropathy.

Study on the Cutting Damage Mechanism of Aramid Honeycomb Based on the Progressive Damage Model.

A progressive damage model for aramid honeycomb cutting was proposed to reveal its cutting damage mechanism. It established the relationship between the mesoscale failure modes and the macroscale cutting damage types of the aramid honeycomb. The proposed model addressed the material assignment problem of impregnated honeycomb by developing a material calculation method that simulates the real manufacturing process of the aramid honeycomb. Cutting experiment of aramid honeycomb specimen was conducted concerning on the cutting forces response and cutting damages, which validated that the proposed method was effective for investigating the cutting process and mechanism for the aramid honeycomb. Predicted cutting mechanism results show that: (a) cutting process of the aramid honeycomb can be divided into three stages with four characteristic states-initial state, cut-in state, cut-out state and final state; (b) cell wall bending in the cutting direction relieves the cutting force, and strong plasticity of the aramid fiber makes it hard to break, which lead to uncut fiber and burr damages; (c) using sharp tip cutting tool to reduce cutting force and bonding both top and bottom of the honeycomb to make it stiffer are beneficial to obtain good cutting quality with less damages.

Clinical predictors for nondiabetic kidney diseases in patients with type 2 diabetes mellitus: a retrospective study from 2017 to 2021.

BACKGROUND: Nondiabetic kidney disease (NDKD), which is prevalent among patients with diabetes mellitus (DM), is considerably different from diabetic kidney disease (DKD) in terms of the pathological features, treatment strategy and prognosis. Although renal biopsy is the current gold-standard diagnostic method, it cannot be routinely performed due to a range of risks. The aim of this study was to explore the predictors for differentiating NDKD from DKD to meet the urgent medical needs of patients who cannot afford kidney biopsy. METHODS: This is a retrospective study conducted by reviewing the medical records of patients with type 2 DM who underwent percutaneous renal biopsy at the Affiliated Hospital of Guizhou Medical University between January 2017 and May 2021. The demographic data, clinical data, blood test results, and pathological examination results of the patients were obtained from their medical records. Multivariate regression analysis was performed to evaluate the predictive factors for NDKD. RESULTS: A total of 244 patients were analyzed. The median age at biopsy was 55 (46, 62) years. Patients diagnosed with true DKD, those diagnosed with NDKD and those diagnosed with NDKD superimposed DKD represented 48.36% (118/244), 45.9% (112/244) and 5.74% (14/244), respectively, of the patient population. Immunoglobulin A nephropathy was the most common type of lesion in those with NDKD (59, 52.68%) and NDKD superimposed DKD (10, 71.43%). Independent predictive indicators for diagnosing NDKD included a DM duration of less than 5 years (odds ratio [OR] = 4.476; 95% confidence interval [CI]: 2.257-8.877; P < 0.001), an absence of diabetic retinopathy (OR = 4.174; 95% CI: 2.049-8.502; P < 0.001), a high RBC count (OR = 1.901; 95% CI: 1.251-2.889; P = 0.003), and a negative of urinary glucose excretion test result (OR = 2.985; 95% CI: 1.474-6.044; P = 0.002).. CONCLUSIONS: A DM duration less than 5 years, an absence of retinopathy, a high RBC count and an absence of urinary glucose excretion were independent indicators for the diagnosis of NDKD, suggesting that patients with NDKD may require a different treatment regimen than those with DKD.

The development of a candidate of desensitization vaccines against Der f 2 nearly without IgE-binding activity.

Considering the important role of Der f 2 in house dust mites mediating allergic diseases and allergic adverse effects during allergen-specific immunotherapy (AIT), we intend to develop a candidate of desensitization vaccines against Der f 2 without allergenicity. According to the reported immunoglobulin E (IgE)-binding B and T cell epitopes of Der f 2, four candidates of desensitization vaccines against Der f 2 were developed. Recombinant wild-type Der f 2 (rWt-Der f 2) preserved conformational and linear IgE-binding B epitopes. rWt-Der f 2 linearized by reduction and alkylation reactions (rWt-Der f 2 (red/alk)) and recombinant modified-type Der f 2 (rMt-Der f 2) were developed via destroying conformational and linear IgE-binding B epitopes respectively. rMt-Der f 2 linearized by reduction and alkylation reactions (rMt-Der f 2 (red/alk)) was developed by destroying conformational and linear IgE-binding B epitopes. T cell epitopes of 4 candidates were preserved. The change of their IgE-binding activity was determined by enzyme linked immunosorbent assay (ELISA), western blot and inhibition ELISA. Compared with rWt-Der f 2, the IgE-binding activity of rWt-Der f 2 (red/alk), rMt-Der f 2 and rMt-Der f 2 (red/alk) all decreased, which was consistent with the result of western blot. The IgE-binding activity of rMt-Der f 2 and rMt-Der f 2 (red/alk) was not significantly different (P = 0.0863 > 0.05), which was comparable to that of their corresponding negative controls (P = 0.3488 and 0.4459, both > 0.05). The result of inhibition ELISA also showed that their IgE-binding activity decreased, and rMt-Der f 2 (red/alk) was the lowest. Conclusively, we developed the candidate of desensitization vaccines against Der f 2, rMt-Der f 2 or rMt-Der f 2 (red/alk), nearly without allergenicity, which would potentially prevent HDM allergic patients from allergic adverse effects caused by AIT.

Chaperone Copolymer Assisted G-Quadruplex-Based Signal Amplification Assay for Highly Sensitive Detection of VEGF.

Vascular endothelial growth factor (VEGF) is a critical biomarker in the angiogenesis of several cancers. Nowadays, novel approaches to rapid, sensitive, and reliable VEGF detection are urgently required for early cancer diagnosis. Cationic comb-type copolymer, poly(L-lysine)-graft-dextran (PLL-g-Dex) accelerates DNA hybridization and chain exchange reaction while stabilizing the DNA assembly structure. In this work, we examined the chaperone activity of PLL-g-Dex to assist G-quadruplex-based fluorescent DNA biosensors for sensitive detection of VEGF. This convenient and effective strategy is based on chitosan hydrogel, c-myc, Thioflavin T (ThT), VEGF aptamer, and its partially complementary strand. The results show that chaperone copolymer PLL-g-Dex significantly promotes the accumulation of G-quadruplex and assembles into G-wires, allowing an effective signal amplification. Using this method, the detection limit of VEGF was as low as 23 pM, better than many previous works on aptamer-based VEGF detection. This chaperone copolymer-assisted signal amplification strategy has potential applications in the highly sensitive detection of target proteins, even including viruses.

Signal-On Fluorescence Biosensor for Highly Sensitive Detection of miRNA-21 Based on DNAzyme Assisted Double-Hairpin Molecular Beacon.

Although miRNAs exist in small quantities in the human body, they are closely related to the abnormal expression of genes in diseases such as tumors. Therefore, sensitive detection of miRNAs is very important for the prevention and treatment of various tumors and major diseases. The purpose of this study is to develop a label-free sensing strategy based on the co-action of double-hairpin molecular beacons and deoxyribozymes (DNAzymes) for highly sensitive detection of miRNA-21. The target miRNA-21 promotes the assembly of DNAzyme with a complete catalytic core region. At the presence of Mg2+, DNAzyme cuts a substrate into short chains, which open the double hairpin molecular beacon, and then form G-quadruplexs at both ends, specifically binding more ThT to generate a amplified fluorescent signal. The cut substrate will be replaced by the uncut ones in the next stage, increasing the concentration of reactants, and thus further improving the fluorescence intensity. This DNAzyme assisted double hairpin molecular beacon has a certain degree of discrimination for substances with single base mismatches, and the detection limit of miRNA-21 is 0.13 pM, lower than that of the many other analysis. Further, this detection has good selectivity and sensitivity in serum. Therefore, this strategy provides a simple, fast and low-cost platform for the sensitive detection of miRNA-21, having potential applications in early cancer diagnosis.

A DNA Electrochemical Sensor via Terminal Protection of Small-Molecule-Linked DNA for Highly Sensitive Protein Detection.

The qualitative and quantitative determination of marker protein is of great significance in the life sciences and in medicine. Here, we developed an electrochemical DNA biosensor for protein detection based on DNA self-assembly and the terminal protecting effects of small-molecule-linked DNA. This strategy is demonstrated using the small molecule biotin and its receptor protein streptavidin (SA). We immobilized DNA with a designed structure and sequence on the surface of the gold electrode, and we named it M1-Biotin DNA. M1-Biotin DNA selectively combines with SA to generate M1-Biotin-SA DNA and protects M1-Biotin DNA from digestion by EXO III; therefore, M1-Biotin DNA remains intact on the electrode surface. M1-Biotin-SA DNA was modified with methylene blue (MB); the MB reporter molecule is located near the surface of the gold electrode, which generates a substantial electrochemical signal during the detection of SA. Through this strategy, we can exploit the presence or absence of an electrochemical signal to provide qualitative target protein determination as well as the strength of the electrochemical signal to quantitatively analyze the target protein concentration. This strategy has been proven to be used for the quantitative analysis of the interaction between biotin and streptavidin (SA). Under optimal conditions, the detection limit of the proposed biosensor is as low as 18.8 pM, and the linear range is from 0.5 nM to 5 µM, showing high sensitivity. The detection ability of this DNA biosensor in complex serum samples has also been studied. At the same time, we detected the folate receptor (FR) to confirm that this strategy can be used to detect other proteins. Therefore, this electrochemical DNA biosensor provides a sensitive, low-cost, and fast target protein detection platform, which may provide a reliable and powerful tool for early disease diagnosis.

Clinical Observation of Prophylactic Extended-Field Intensity-Modulated Radiation Therapy with Synchronous Chemotherapy in Locally Advanced Cervical Cancer.

BACKGROUND We aimed to evaluate the value of prophylactic extended-field intensity-modulated radiation therapy (IMRT) in the treatment of locally advanced cervical cancer with multiple pelvic lymph node metastases (≥2) and negative common iliac and paraaortic lymph nodes. MATERIAL AND METHODS Thirty-four patient with newly diagnosed cervical cancer (IB1-IVA) and multiple pelvic lymph node metastases (≥2) confirmed by computed tomography and magnetic resonance imaging were randomly divided into an extended-field group (17 patients) and a pelvic-field group (17 patients). In the extended-field group, we added the drainage area of paraaortic lymph nodes on the pelvic field. The pelvic field was administered Dt 45.0 to 50.4 Gy, while the drainage area of paraaortic lymph nodes was administered Dt 40.0 to 45.0 Gy. Both groups were given Irl92 intracavitary radiotherapy after 3 weeks of external irradiation. The total dose of point A was 25.0 to 30.0 Gy, fractional 6.0 to 7.0 Gy. All patients had concurrent platinum-based chemotherapy once weekly until the end of radiotherapy. RESULTS No paraaortic lymph node metastasis was found in the extended-field group (P=0.0184), and disease-free survival (DFS) was prolonged (P=0.0286). Adverse effects in patients with III-IV degree myelosuppression were increased in the extended-field group (P=0.0324). However, all patients recovered after symptomatic treatment. CONCLUSIONS Prophylactic extended-field IMRT with chemotherapy reduced the metastasis rate of paraaortic lymph nodes and prolonged the DFS in patients with locally advanced cervical cancer and multiple pelvic lymph node metastases (≥2), while the toxic adverse effects were tolerated.

MMP-16 as a New Biomarker for Predicting Prognosis and Chemosensitivity of Serous Ovarian Cancer: A Study Based on Bioinformatics Analysis.

OBJECTIVE: To explore the prognostic value of MMP-16 expression in patients with serous ovarian cancer and the usefulness of MMP-16 expression to predict sensitivity to chemoradiotherapy. METHODS: The relationship between MMP-16 expression and clinicopathological parameters of serous ovarian cancer was evaluated in The Cancer Genome Atlas (TCGA) database. Cox proportional hazard regression analysis was performed to measure the prognostic significance of MMP-16 in serous ovarian cancer. Dataset GSE51373 was applied to estimate the difference of MMP-16 expression between chemotherapy-sensitive group and resistant group of serous ovarian cancer. Receiver operating characteristic (ROC) curve was also drawn. In addition, the online tool Kaplan-Meier Plotter was used to assess the prognostic value of MMP-16 in patients with serous ovarian cancer. RESULTS: A total of 235 patients with serous ovarian cancer were included in the TCGA database. Cox regression univariate analysis showed that high expression of MMP-16 was not conducive to the overall survival of patients with serous ovarian cancer (hazard ratio [HR] = 1.47, 95% CI: 1.03~2.08; P < 0.05). The results of Cox regression multivariate analysis also demonstrated that there was a statistically significant difference. The results of the online database Kaplan-Meier Plotter analysis showed that the high expression of MMP-16 was not conducive to the progression-free survival (PFS) of patients with serous ovarian cancer (HR = 1.26, 95% CI: 1.06~1.29; P < 0.05). The expression of MMP-16 in the chemotherapy-sensitive group was notably lower than that in the chemotherapy-resistant group, which had a moderate predictive value in predicting the chemosensitivity of serous ovarian cancer (AUC = 0.7187). CONCLUSION: High expression of MMP-16 is not conducive to chemotherapy sensitivity and survival of patients with serous ovarian cancer, and has predictive value for chemotherapy resistance and prognosis.

MiRNA Detection Using a Rolling Circle Amplification and RNA-Cutting Allosteric Deoxyribozyme Dual Signal Amplification Strategy.

A microRNA (miRNA) detection platform composed of a rolling circle amplification (RCA) system and an allosteric deoxyribozyme system is proposed, which can detect miRNA-21 rapidly and efficiently. Padlock probe hybridization with the target miRNA is achieved through complementary base pairing and the padlock probe forms a closed circular template under the action of ligase; this circular template results in RCA. In the presence of DNA polymerase, RCA proceeds and a long chain with numerous repeating units is formed. In the presence of single-stranded DNA (H1 and H2), multi-component nucleic acid enzymes (MNAzymes) are formed that have the ability to cleave substrates. Finally, substrates containing fluorescent and quenching groups and magnesium ions are added to the system to activate the MNAzyme and the substrate cleavage reaction, thus achieving fluorescence intensity amplification. The RCA-MNAzyme system has dual signal amplification and presents a sensing platform that demonstrates broad prospects in the analysis and detection of nucleic acids.