Single polymeric microfiber waveguide platform for sensitive detection and discrimination of DNA methylation.

The development of a rapid and sensitive detection platform for DNA and DNA methylation in complex biological environments has attracted considerable attention. Herein, we describe a detection platform for p16 and p16 methylation in buffer and serum based on a single polymeric fluorescent microfiber waveguide with sandwich-structured hybridization designs. The target p16 could be captured by oligonucleotides conjugated on the surface of polymeric microfibers and oligonucleotides conjugated with gold nanoparticles, resulting in quenching the out-coupled tip emission of the microfiber waveguide. Then the restriction digestion enzyme HpaII was applied to specifically recognize the unmethylated 5'-CCGG-3' site and cut the formed sandwich structure. The gold nanoparticles could be removed from the surface of chitosan fiber so that the out-coupled tip emission of the polymeric fluorescent microfiber would be partially recovered. It is noteworthy that the proposed polymeric microfiber waveguide platform exhibited selective and sensitive detection of p16 with a low limit of 2 pM and excellent analytical performance of methylation as low as 5% difference. This strategy avoids the use of traditional PCR-based amplification and tedious operative processes, and we envisage that this technique could be extended to various DNA methylation analyses, which is meaningful for early clinical diagnosis of diseases.

Enantioselective cytotoxicity of chiral polymer vesicles with linear and hyperbranched structures.

Herein, we study the enantioselective cytotoxicity of vesicles self-assembled by optically active linear polymers (LNPs) and hyperbranched polymers (HBPs). Compared to HBP vesicles, LNP vesicles exhibit properties such as a higher surface charge density and more violent interaction with simulated biomembranes which results in larger cytotoxicity against HeLa cells. Specifically, racemic-LNP vesicles exhibit the largest cytotoxicity of all. More interestingly, there is no significant enantioselective dependence of HBP vesicles on the abovementioned properties. Overall, we proved that the cytotoxicity of vesicles is deeply related to chirality and topological-structures. This research is of great fundamental value for the design of novel bio-interface materials.

Identification of Independent Risk Factors for Complications: A Retrospective Analysis of 163 Fibular Free Flaps for Mandibulofacial Reconstruction.

PURPOSE: Fibular free flap transfer is a powerful tool available to the reconstructive surgeon when treating oral and maxillofacial defects, but complications still occasionally occur and predictive analysis focusing on this specific flap is limited in terms of risk factors for complication. The purpose of this study was to identify key variables associated with complications in patients undergoing fibular free flap transfer. PATIENTS AND METHODS: The data of 163 consecutive patients who underwent fibular free flap surgery at the Department of Oral and Maxillofacial Surgery, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, between 2012 and 2015 were reviewed retrospectively. Patient demographic data, laboratory data, surgical data, and fluid infusion-related data that may have an influence on free flap outcomes were recorded. Univariate and multivariate logistic regression analyses were used to identify relevant risk factors. RESULTS: A total of 163 fibular free flaps were transferred for mandibulofacial reconstruction in 163 patients with a mean age of 50.9 years. Postoperative complications developed in 33 (20.2%). Multivariate analysis showed that free flap complications were significantly associated with radiotherapy history (odds ratio [OR], 5.12; P = .001), postoperative anemia (OR, 1.048; P = .041), postoperative hypoalbuminemia (OR, 0.844; P = .002), and prolonged operative time (OR, 1.005; P = .004). CONCLUSIONS: Radiotherapy history, decreased postoperative hemoglobin and albumin levels, and prolonged operative time are potential predictors of postoperative complications after fibular free flap reconstruction for mandibulofacial defects.

Diagnostic value of combined ultrasound contrast and elastography for differentiating benign and malignant thyroid nodules: a meta-analysis.

The diagnostic value of contrast-enhanced ultrasound combined with ultrasound elastography for benign and malignant thyroid nodules is still controversial, so we used meta-analysis to seek controversial answers. The PubMed, OVID, and CNKI databases were searched according to the inclusion and exclusion criteria. The literature was selected from the establishment of each database to February 2024. The QUADAS-2 tool assessed diagnostic test accuracy. SROC curves and Spearman's correlation coefficient were made by Review Manager 5.4 software to assess the presence of threshold effects in the literature. Meta-Disc1.4 software was used for Cochrane-Q and χ2 tests, which be used to evaluate heterogeneity, with P-values and I2 indicating heterogeneity levels. The appropriate effect model was selected based on the results of the heterogeneity test. Stata18.0 software was used to evaluate publication bias. The diagnostic accuracy of contrast-enhanced ultrasound combined with ultrasound elastography for benign and malignant thyroid nodules was evaluated by calculating the combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, DOR, and area under the SROC curve. A total of 31 studies included 3811 patients with 4718 nodules were analyzed. There is no heterogeneity caused by the threshold effect, but there is significant non-threshold heterogeneity. Combined diagnostic metrics were: sensitivity = 0.93, specificity = 0.91, DOR = 168.41, positive likelihood ratio = 10.60, and negative likelihood ratio = 0.07. The SROC curve area was 0.97. Contrast-enhanced ultrasound and elastography show high diagnostic accuracy for thyroid nodules, offering a solid foundation for early diagnosis and treatment.Trial registration. CRD42024509462.

Sensitive discrimination of single nucleotide variants using a PDA microtube waveguide platform with heterogeneous CHA amplification and competitive inhibition strategy.

Here, we present a novel PDA microtube waveguide platform by combining heterogeneous CHA amplification with competitive inhibition. The heterogeneous CHA amplification system can preferentially amplify the signal of the correct target, while the competitive inhibition system will preferentially bind with the mutant targets and inactivate their signal.

LncRNA THOR promotes tongue squamous cell carcinomas by stabilizing IGF2BP1 downstream targets.

THOR, a highly conserved lncRNA, is potentially involved in various cancer development. However, its involvement in tongue squamous cell carcinoma (TSCC) remains unclear. The present study aims to explore the biological function and molecular mechanism of THOR in TSCC progression. The expressions of THOR and IGF2BP1 in TSCC tissues and adjacent non-cancerous tongue tissues (ANT) were examined through qRT-PCR. THOR levels were manipulated in TSCC cells to explore its function in cancer progression in vitro and in vivo, which were subsequently evaluated by CCK8, colony formation assay, flow cytometry, xenograft tumor assays. In situ hybridization, RIP and Western blot assay were performed to explore the underlying molecular mechanisms. We discovered that THOR and IGF2BP1 were dramatically upregulated in TSCC tissues. The expression of THOR is positively correlated with IGF2BP1 mRNA level. THOR mediated IGF2 expression via interacting with IGF2BP1, and affected the downstream MEK-ERK signaling pathway to regulate TSCC cells proliferation. THOR/IGF2BP1/IGF2-MEK-ERK axis regulated the proliferation of TSCC cells, implying that THOR would be a promising therapeutic target for TSCC patients.

Integrating PDA microtube waveguide system with heterogeneous CHA amplification strategy towards superior sensitive detection of miRNA.

Catalytic hairpin assembly (CHA) is a typical enzyme-free amplification strategy, in which the target can catalyze two hairpin probes to form a duplex and yield multiple outputs signal. However, the non-specific hybridization of two hairpin probes in CHA circuit usually occurred even in the absence of target, causing significant background leakage and impeding its practical applications in trace miRNA analysis. Herein, we proposed a novel heterogeneous CHA (hetero-CHA) design integrating with PDA microtube waveguide system, offering the advantages to enhance the target signal, but suppress the background leakage simultaneously. In hetero-CHA strategy, single-stranded targets are enriched nearby the surface of PDA microtube, facilitating the target-triggered CHA amplification and strand displacement reactions. In contrast, double-stranded DNA complexes formed by uncatalyzed hybridizations are isolated from PDA microtube, impeding the leakage signal. By combination with condensing enrichment effect, the proposed hetero-CHA probe exhibited high selectivity and sensitivity to miRNA target, giving a detection limit as low as 3.3 fM. More importantly, the proposed hetero-CHA probe can be applied directly to distinguish the expression of miRNA-21 in clinical serum of cancer patients (including lung, breast and pancreatic) from those of healthy human beings, favoring the cancer diagnosis and therapeutic evaluation.

Single polydiacetylene microtube waveguide platform for discriminating microRNA-215 expression levels in clinical gastric cancerous, paracancerous and normal tissues.

MicroRNAs (miRNAs) have emerged as novel biomarkers for human early-phase cancer diagnosis and disease prevention recently. Herein, we reported a novel miRNA-215 targeting biosensor, which was based on single polydiacetylene (PDA) microtube waveguide system integrated with sandwich-type hybridization design and condensing enrichment effect. The target miRNA could be captured by oligonucleotides conjugated on the surface of PDA microtube and Au nanorod (AuNR) respectively, resulting in the out-coupled fluorescence of PDA microtube quenching. In this strategy, the formation of a sandwich structure, as a result of co-hybridization of the target miRNA, enabled simplified preparation process, enhanced reaction efficiency, and increased recyclability and stability of the platform. Based on condensing enrichment effect, the co-hybridization reaction could be enriched on the surface of microtube and the proposed platform could easily achieve highly sensitive detection of miRNA-215 in one step. Remarkably, this platform could be directly applied to discriminate the miRNA-215 expression levels in clinical gastric cancerous, paracancerous and normal tissues samples. This assay offers a simple and convenient method for miRNA quantification in clinical samples, even with the potential for invasive, portable equipment for early clinical diagnosis of diseases.

Effect of c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (p38 MAPK) in morphine-induced tau protein hyperphosphorylation.

Opioids have been widely used in clinical practice as potent pain relievers for centuries. However, opioids have many deleterious effects. It has been reported that opioid increases tau protein phosphorylation. Hyperphosphorylation of tau is also a pathological feature of Alzheimer's disease and other chronic neurodegenerative disorders. However, the underlying mechanism by which opioids enhance tau phosphorylation is not yet known. In this study, we treated rat embryo cortical neurons with morphine and observed its effect on tau phosphorylation. We found that morphine induced tau hyperphosphorylation and increased levels of phospho-JNK and phospho-p38; these effects were blocked by pretreatment with naloxone. Inhibition of JNK by SP600125 significantly reduced tau hyperphosphorylation in neurons treated with morphine. Similarly, SB203580, an antagonist of p38 MAPK, abolished tau hyperphosphorylation in neurons treated with morphine. Our data suggest that JNK/p38 MAPK, activated by morphine in an opioid receptor-dependent manner, may lead to tau hyperphosphorylation.