Shining a light on liver health: advancements in fluorescence-enhanced enzyme biosensors for early disease detection.

Early detection of liver diseases holds paramount importance in optimizing treatment outcomes and prognosis, thereby significantly enhancing the likelihood of recovery while mitigating the risk of progression to liver cancer. Liver diseases encompass a spectrum of conditions, each potentially manifesting distinct enzymatic profiles. Monitoring these enzymes in situ facilitates timely intervention and therapeutic management. In recent years, the field of biosensor technology has witnessed remarkable advancement, owing to strides in biomedicine and computational sciences. Biosensors have garnered widespread utility across medical and biological domains, spanning the detection of disease biomarkers, drug release tracking, ion imaging, and fluorescence imaging within living organisms. These applications have markedly enhanced imaging resolution and have the potential to refine disease diagnosis accuracy for clinicians. A pivotal aspect in the successful application of this technology lies in the construction of fluorescence probes adept at swiftly and selectively identifying target enzymes by amalgamating liver disease enzymes with fluorescence probe technology. However, research in this niche area remains relatively scarce. Building upon this foundational understanding, the present review delineates the utilization of biosensors in the early diagnosis of liver disease. Serving as a theoretical framework, this review envisages the development of high-performance biosensors tailored for the early detection of liver cancer. Furthermore, it offers insights into the potential of biosensor technology to progress and broaden its practical applications, thus contributing to the advancement of diagnostic methodologies in liver disease management.

Crosstalk among disulfidptosis-related lncRNAs in lung adenocarcinoma reveals a correlation with immune profile and clinical prognosis.

Disulfidptosis refers to a specific programmed cell death process characterized by the accumulation of disulfides. It has recently been reported in several cancers. However, the impact of disulfidptosis-related long non-coding RNAs (lncRNAs) on malignant tumors has remained largely unknown. In the present work, we screened prognostic disulfidptosis-related lncRNAs and studied their effects on lung adenocarcinoma. Relevant clinical data of lung adenocarcinoma cases were retrieved from The Cancer Genome Atlas (TCGA) database. RNA sequencing was used to identify differentially expressed disulfidptosis-related lncRNAs within lung adenocarcinoma. In addition, prognostic disulfidptosis-related lncRNAs were obtained through univariate Cox regression analysis. LASSO-COX was used to construct new disulfidptosis-related lncRNA signatures. Different statistical approaches were used to validate the practicability and accuracy of the disulfidptosis-related lncRNAs signatures. Furthermore, several bioinformatic approaches were used to study relevant heterogeneities in biological processes and pathways of diverse risk groups. Reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) was conducted to analyze the expression of disulfidptosis-related lncRNAs. Finally, seven disulfidptosis-related lncRNA signatures were identified in lung adenocarcinoma cells. The prognosis prediction model constructed efficiently predicted patient survival. Subgroup analysis revealed significant differences in immune cell proportion, including T follicular helper cells and M0 macrophages. In addition, in vitro experimental results demonstrated significant differences in disulfidptosis-related lncRNAs. Altogether, the six disulfidptosis-related lncRNA signatures could serve as a potential prognostic biomarker for lung adenocarcinoma. Furthermore, these can be used as a prediction model in individualized immunotherapy for lung adenocarcinoma.

Transcriptome Analysis Reveals the Molecular Mechanisms of BR Negative Regulatory Factor StBIN2 Maintaining Tuber Dormancy.

Potato is an important food crop. After harvest, these tubers will undergo a period of dormancy. Brassinosteroids (BRs) are a new class of plant hormones that regulate plant growth and seed germination. In this study, 500 nM of BR was able to break the dormancy of tubers. Additionally, exogenous BR also upregulated BR signal transduction genes, except for StBIN2. StBIN2 is a negative regulator of BR, but its specific role in tuber dormancy remains unclear. Transgenic methods were used to regulate the expression level of StBIN2 in tubers. It was demonstrated that the overexpression of StBIN2 significantly prolonged tuber dormancy while silencing StBIN2 led to premature sprouting. To further investigate the effect of StBIN2 on tuber dormancy, RNA-Seq was used to analyze the differentially expressed genes in OE-StBIN2, RNAi-StBIN2, and WT tubers. The results showed that StBIN2 upregulated the expression of ABA signal transduction genes but inhibited the expression of lignin synthesis key genes. Meanwhile, it was also found that StBIN2 physically interacted with StSnRK2.2 and StCCJ9. These results indicate that StBIN2 maintains tuber dormancy by mediating ABA signal transduction and lignin synthesis. The findings of this study will help us better understand the molecular mechanisms underlying potato tuber dormancy and provide theoretical support for the development of new varieties using related genes.

A comparison of machine learning methods to find clinical trials for inclusion in new systematic reviews from their PROSPERO registrations prior to searching and screening.

Searching for trials is a key task in systematic reviews and a focus of automation. Previous approaches required knowing examples of relevant trials in advance, and most methods are focused on published trial articles. To complement existing tools, we compared methods for finding relevant trial registrations given a International Prospective Register of Systematic Reviews (PROSPERO) entry and where no relevant trials have been screened for inclusion in advance. We compared SciBERT-based (extension of Bidirectional Encoder Representations from Transformers) PICO extraction, MetaMap, and term-based representations using an imperfect dataset mined from 3632 PROSPERO entries connected to a subset of 65,662 trial registrations and 65,834 trial articles known to be included in systematic reviews. Performance was measured by the median rank and recall by rank of trials that were eventually included in the published systematic reviews. When ranking trial registrations relative to PROSPERO entries, 296 trial registrations needed to be screened to identify half of the relevant trials, and the best performing approach used a basic term-based representation. When ranking trial articles relative to PROSPERO entries, 162 trial articles needed to be screened to identify half of the relevant trials, and the best-performing approach used a term-based representation. The results show that MetaMap and term-based representations outperformed approaches that included PICO extraction for this use case. The results suggest that when starting with a PROSPERO entry and where no trials have been screened for inclusion, automated methods can reduce workload, but additional processes are still needed to efficiently identify trial registrations or trial articles that meet the inclusion criteria of a systematic review.

A Rapid and Simplified Method to Isolate Specific Regulators Based on Biotin-Avidin Binding Affinities in Crops.

Transcription factors (TFs) are indispensable components of transcriptional regulatory pathways involved in crop growth and development. Herein, we developed a new method for the identification of upstream TFs specific to genes in crops based on the binding affinities of biotin and avidin. First, we constructed and verified the new biotin and avidin system (BAS) by a coprecipitation assay. Subsequently, the feasibility of DNA-based BAS (DBAS) was further proved by in vivo and in vitro assays. Furthermore, we cloned the promoter of rice OsNRT1.1B and the possible regulators were screened and identified. Additionally, partial candidates were validated by the electrophoresis mobility shift assay (EMSA), yeast one-hybrid, and luciferase activity assays. Remarkably, the results showed that the candidates PIP3 and PIP19 both responded to nitrate immediately and overexpression of PIP3 caused retard growth, which indicates that the candidates are functional and the new DBAS method is useful to isolate regulators in crops.

StSN2 interacts with the brassinosteroid signaling suppressor StBIN2 to maintain tuber dormancy.

After harvest, potato tubers undergo an important period of dormancy, which significantly impacts potato quality and seed vigor. StSN2 has been reported as a key gene for maintaining tuber dormancy; in this study, we explored the molecular mechanism by which StSN2 maintains dormancy. StBIN2 was first identified as a candidate protein that interacts with StSN2 by co-immunoprecipitation/mass spectrometry, and both qPCR and enzyme activity experiments showed that StSN2 can promote the StBIN2 expression and activity. In addition, the interaction between StSN2 and StBIN2 was verified by yeast two-hybrid, luciferase complementation experiments and co-immunoprecipitation. Bioinformatics analysis and site-directed mutagenesis confirmed the critical role of cysteine residues of StBIN2 in its binding to StSN2. Similar to that of StSN2, overexpression of StBIN2 extended the dormancy of potato tuber. Interaction between StSN2 and StBIN2 increased the activity of the StBIN2 enzyme, inhibited the expression of StBZR1, and suppressed BR signaling. On the contrary, this interaction promoted the expression of StSnRK2.2/2.3/2.4/2.6 and StABI5, key genes of ABA signaling, and the phosphorylation of StSnRK2.3, thereby promoting ABA signaling. Altogether, our results indicate that StSN2 interacts with StBIN2 through key cysteine residues and StBIN2 maintains tuber dormancy by affecting ABA and BR signaling. Findings of this research offer new insights into the molecular mechanism by which StSN2 maintains potato tuber dormancy through interaction with StSIN2 and provide guidance for potato improvement.

StBIN2 Positively Regulates Potato Formation through Hormone and Sugar Signaling.

Potato is an important food crop worldwide. Brassinosteroids (BRs) are widely involved in plant growth and development, and BIN2 (brassinosteroid insensitive 2) is the negative regulator of their signal transduction. However, the function of BIN2 in the formation of potato tubers remains unclear. In this study, transgenic methods were used to regulate the expression level of StBIN2 in plants, and tuber related phenotypes were analyzed. The overexpression of StBIN2 significantly increased the number of potatoes formed per plant and the weight of potatoes in transgenic plants. In order to further explore the effect of StBIN2 on the formation of potato tubers, this study analyzed BRs, ABA hormone signal transduction, sucrose starch synthase activity, the expression levels of related genes, and interacting proteins. The results show that the overexpression of StBIN2 enhanced the downstream transmission of ABA signals. At the same time, the enzyme activity of the sugar transporter and the expression of synthetic genes were increased in potato plants overexpressing StBIN2, which also demonstrated the upregulation of sucrose and the expression of the starch synthesis gene. Apparently, StBIN2 affected the conversion and utilization of key substances such as glucose, sucrose, and starch in the process of potato formation so as to provide a material basis and energy preparation for forming potatoes. In addition, StBIN2 also promoted the expression of the tuber formation factors StSP6A and StS6K. Altogether, this investigation enriches the study on the mechanism through which StBIN2 regulates potato tuber formation and provides a theoretical basis for achieving a high and stable yield of potato.

Nanotechnology for brain tumor imaging and therapy based on π-conjugated materials: state-of-the-art advances and prospects.

In contemporary biomedical research, the development of nanotechnology has brought forth numerous possibilities for brain tumor imaging and therapy. Among these, π-conjugated materials have garnered significant attention as a special class of nanomaterials in brain tumor-related studies. With their excellent optical and electronic properties, π-conjugated materials can be tailored in structure and nature to facilitate applications in multimodal imaging, nano-drug delivery, photothermal therapy, and other related fields. This review focuses on presenting the cutting-edge advances and application prospects of π-conjugated materials in brain tumor imaging and therapeutic nanotechnology.

Study on Porosity of Thermal-Sprayed Commercially Pure Aluminum Coating.

Porosity is closely related to the corrosion and wear properties of a coating processed by thermal-spraying technology, and the quantitative characterization of porosity is a crucial part of the research on coating structures. The current image analysis method often uses the mechanical polishing method recommended by ISO to measure a coating porosity. This method has been proved to be an effective method for the characterization of oxide coatings. However, due to the significant differences in the physical and chemical properties between aluminum and oxides, this method may not be suitable for aluminum coatings, and a more appropriate approach needs to be explored. In this paper, the effects of three polishing technologies (mechanical polishing, argon-ion-beam polishing, and electrolytic polishing) on the porosity measurement of pure aluminum coatings were compared and studied. The research results showed that the commonly used mechanical polishing method and more advanced argon-ion-beam polishing method could not completely reveal the pore structure because SiC particles would be embedded in the pure aluminum coatings during mechanical polishing, filling large pores. Although electrolytic polishing technology had advantages in revealing the macroporous structure, it would introduce a microporous structure and oxides, which would affect the measurement of the coating porosity. The composite polishing technology (electrolytic polishing + argon-ion-beam polishing) could perfectly reveal the pore structure in the pure-aluminum coating, and the porosity of arc-sprayed aluminum coating was 9.9%, which was close to the macroscopic true value measured using the weighing method of 10.2%.

Clinical outcomes of radioactive seed brachytherapy and microwave ablation in inoperable stage I non-small cell lung cancer.

This study assessed the efficacy and safety of radioactive iodine-125 seed ablation brachytherapy (RSABT) in comparison to microwave ablation therapy (MWAT) for treating inoperable stage I non-small cell lung cancer (NSCLC). We conducted a retrospective analysis of data from stage I NSCLC patients who underwent CT-guided RSABT or MWAT. The primary outcomes measured were progression-free survival (PFS), overall survival (OS), and the occurrence of adverse events. Of the patients included in the study, 71 underwent RSABT and 105 received MWAT. The median follow-up time for these groups was 47.4 months and 60 months, respectively. The PFS rates at 1-year, 3-year, and 5-year for the RSABT group were 87.3%, 72.6%, and 65.8%, while for the MWAT group, they were 89.5%, 69.3%, and 43.7%, respectively (P = 0.011). The OS rates at 1-year, 3-year, and 5-year for the RSABT group were 97.2%, 78.1%, and 66.1%, and for the MWAT group, they were 99%, 75.8%, and 55%, respectively (P = 0.112). Upon multivariate analysis, the treatment modality was identified as an independent predictor of PFS (P = 0.008). Additionally, both sex and T stage were found to be independent predictors of both PFS and OS (P < 0.05). Adverse events, such as pneumothorax, occurred in 50% of the MWAT group and 39% of the RSABT group (P = 0.313). The incidence of pleural effusion was 44% in the MWAT group compared to 14% in the RSABT group (P < 0.001). Needle bleeding was observed in 32% of the RSABT group and 5% of the MWAT group (P < 0.001). We conclude RSABT demonstrates promising efficacy and safety in the treatment of stage I NSCLC. However, further studies are essential to validate these preliminary findings.

Humanized disulfide-stabilized diabody against fibroblast growth factor-2 inhibits PD-L1 expression and epithelial-mesenchymal transition in hepatoma cells through STAT3.

Fibroblast growth factor 2 (FGF2) plays an important role in tumor angiogenesis. Humanized disulfide-stable double-chain antibody against fibroblast growth factor-2 (anti-FGF2 ds-Diabody) is a small molecule antibody with good tissue permeability and low immunogenicity, which has potential in tumor-targeted therapy. This study intended to investigate the effect of anti-FGF2 ds-Diabody on the migration and expression of programmed death-ligand1 (PD-L1) in hepatocellular carcinoma (HCC) cells. The anti-FGF2 ds-Diabody was expressed under methanol induction and purified with Ni2+ -affinity chromatography. Anti-FGF2 ds-Diabody significantly inhibited cell viability and proliferation in SK-Hep1 and HepG2 cells as confirmed by CCK-8 assays and colony formation assays. Western blot assays indicated that the proliferation of SK-Hep1 and HepG2 cells was inhibited by anti-FGF2 ds-Diabody through inhibiting the phosphorylation activation of AKT and MAPK. The results of transwell and western blot assays showed that the migration and invasion of SK-Hep1 and HepG2 cells were suppressed by anti-FGF2 ds-Diabody by affecting the epithelial-mesenchymal transition (EMT) process. Meanwhile, anti-FGF2 ds-Diabody inhibited the expression of PD-L1, and STAT3 participated in this process. Analysis of RT-PCR and Western blot suggested that fibroblast growth factor receptor 4 inhibitor 1 (FGFR4-IN-1) suppressed the expression of PD-L1, while STAT3 overexpression reversed this inhibitory effect. In addition, overexpression of STAT3 promoted migration and invasion and restored the suppressive effect of anti-FGF2 ds-Diabody on EMT. In conclusion, anti-FGF2 ds-Diabody could inhibit the expression of PD-L1 and EMT of hepatoma cells through FGF2/FGFR4/STAT3 axis. These results suggested that anti-FGF2 ds-Diabody has potential clinical application in inhibiting metastasis and immune escape of hepatocellular carcinoma.

Coherent dual-frequency signal generation in an optoelectronic oscillator.

Coherent dual-frequency microwave signal generation using an optoelectronic oscillator (OEO) is presented and demonstrated. In the proposed OEO, a dual-band bandpass filter (DB-BPF) is utilized to select two oscillation modes. An external signal is injected into the OEO loop with its frequency equaling the frequency interval of the two oscillation modes. Owing to the modulation nonlinearity of the Mach-Zehnder modulator, the two oscillation frequencies interact with the injection frequency. When the phase and gain conditions are satisfied within the loop, injection locking between the two oscillation signals will be established, and their phases will be synchronized. The effect of gain competition in the OEO loop, which leads to single-frequency oscillation, is suppressed. An experiment is carried out, and two frequencies, of 16.083 GHz and 9.998 GHz, are generated at the same time. The phase noise values are -140.1 and -141.0 dBc/Hz @ 10 kHz, respectively. The coherence between the generated signals and sidemode suppression performance are evaluated.

Comparison of modified U-shaped and inverted L-shaped medial capsulorrhaphy in hallux valgus surgery: a prospective, randomized controlled trial of 75 patients.

PURPOSE: The purpose of this study was to report a modified U-shaped medial capsulorrhaphy and compare its clinical and radiological differences with an inverted L-shaped capsulorrhaphy in hallux valgus (HV) surgery. METHODS: A prospective study of 78 patients was performed between January 2018 and October 2021. All patients underwent chevron osteotomy and soft tissue procedures for HV, and the patients were randomly separated into 2 groups according to the medial capsule closing techniques: a modified U-shaped capsulorrhaphy (group U) and an L-shaped capsulorrhaphy (group L). All patients were followed for at least a year. The preoperative and follow-up data were collected for each patient and included patient demographics, weight-bearing radiographs of the foot, the active range of motion (ROM) of the first metatarsophalangeal (MTP) joint and the American Orthopedic Foot and Ankle Society (AOFAS) forefoot score. Mann-Whitney U test was used for the comparison of the postoperative measures between the groups. RESULTS: In total, 75 patients with 80 affected feet met the inclusion criteria, with 38 patients (41 feet) in group U and 37 patients (39 feet) in group L. One year after surgery, the mean hallux valgus angle (HVA), intermetatarsal angle (IMA), and AOFAS score in group U improved from 29.5 to 7.1, from 13.4 to 7.1, and from 53.4 to 85.5, respectively. The mean HVA, IMA, and AOFAS score in group L improved from 31.2 to 9.6, from 13.5 to 7.9, and from 52.3 to 86.6, respectively. Comparing the 1-year postoperative measures between the 2 groups, a significant difference was found in HVA (P = 0.02), but not found in IMA and AOFAS score (P = 0.25 and P = 0.24, respectively). The mean ROM of the first MTP joint was 66.3 degrees preoperatively and 53.3 degrees at the 1-year follow-up in group U, while 63.3 and 47.5 in group L. The degrees of ROM after 1 year in group U were better than those in group L (P = 0.04). CONCLUSION: Compared to the inverted L-shaped capsulorrhaphy, the modified U-shaped capsulorrhaphy provided a better ROM of the first MTP joint; at 1 year following surgery, the modified U-shaped capsulorrhaphy maintained the normal HVA better.

Template-Free Hydrothermal Synthesis of Octahedron-, Diamond-, and Plate-like ZrO2 Mono-Dispersions.

Anisotropic ZrO2 particles with octahedron-, diamond- and plate-like morphologies are successfully synthesized by a facile hydrothermal treatment approach using NaBF4 as mineralizer. The concentration of mineralizers play a crucial role on the formation of shape-controlled ZrO2 particles thus affect the particle size. With the increasing concentration of mineralizer, the crystalline sizes of the primary single-crystal and the secondary particle size both increase. With the introduction of NaBF4, F- plays an essential role in tuning the crystallinity and size of primary ZrO2 nanorods along [001] direction. The synergistic effect of F- and B3+ result in different epitaxial growth rate. And the secondary particles mainly crystallize on the small primary nanoparticles through the oriented attachment mechanism. The as-prepared ZrO2 particles with different sizes and shapes exhibit different photocatalytic efficiency for the degradation of organic dyes. Under UV irradiation, the highest MB degradation rate of 88% was observed within 60 min for ZrO2 photocatalyst synthesized with 0.01 mol/L NaBF4 mineralizer.

Microwave ablation combined with I125 seed implantation for treatment of residual lesions of liver cancer after TACE.

Context: To compare the efficacy and safety of microwave ablation (MWA) versus MWA combined with I125 seed implantation for the treatment of post-transcatheter arterial chemoembolization (TACE) residual lesions of primary liver cancer. Methods: A total of 38 patients with post-TACE residual lesions of liver cancer only received MWA, whereas 33 patients received combined treatment of MWA with I125 seed implantation. Enhanced magnetic resonance imaging (MRI) or positron emission tomography/computed tomography (PET/CT) was performed for review at 1, 3, and 6 months after treatment to observe and compare the short-term efficacy and complications between the two groups. Results: The tumor complete response (CR) rate of the MWA group after treatment was 55.3% (21/38) and that of the MWA + I125 group was 81.8% (27/33), indicating a significantly higher value than that of the MWA group (P < 0.05). There was no difference in the minor complications between the two groups, and no serious complications were recorded. Conclusions: MWA combined with I125 seed implantation for the treatment of post-TACE residual lesions of primary liver cancer is safe and effective, and its efficacy is better than that of the simple MWA treatment.

ME-PLAN: A deep prototypical learning with local attention network for dynamic micro-expression recognition.

As one of the important psychological stress reactions, Micro-expressions (MEs) are spontaneous and subtle facial movements, which usually occur in a high-stake situation and can reveal genuine human feelings and cognition. ME, Recognition (MER) has essential applications in many fields such as lie detection, criminal investigation, and psychological healing. However, due to the challenges of learning discriminative ME features via fleeting facial subtle reactions as well as the shortage of available MEs data, this research topic is still far from well-studied. To this end, in this paper, we propose a deep prototypical learning framework, namely ME-PLAN, with a local attention mechanism for the MER problem. Specifically, ME-PLAN consists of two components, i.e., a 3D residual prototypical network and a local-wise attention module, where the former aims to learn the precise ME feature prototypes through expression-related knowledge transfer and episodic training, and the latter could facilitate the attention to the local facial movements. Furthermore, to alleviate the dilemma that most MER methods need to depend on manually annotated apex frames, we propose an apex frame spotting method with Unimodal Pattern Constrained (UPC) and further extract ME key-frames sequences based on the detected apex frames to train our proposed ME-PLAN in an end-to-end manner. Finally, through extensive experiments and interpretable analysis regarding the apex frame spotting and MER on composite-database, we demonstrate the superiority and effectiveness of the proposed methods.

Dynamic Collaboration Model of Production Network Based on Cloud Service Bus.

The IT system of manufacturing enterprises usually has many problems, such as complex industrial software, different development languages, diverse communication protocols, and complex operation environment. Cloud service bus (CSB) technology based on service model encapsulates various applications existing in enterprises by means of the integration of cloud service bus and micro services, which can realize the rapid cloud migration and deployment of heterogeneous industrial application software. Theoretically, after the production system is connected to CSB, it can be arranged arbitrarily by service choreography technology to produce any possible products. However, in the context of industrial Internet, the production system connected to CSB corresponds to the equipment, materials, personnel, and other resources on the production line one by one. These production nodes need to consider the production capacity and cost of production service nodes and the output value of the whole production network, and cannot be combined arbitrarily. Therefore, when integrating production service nodes, we should not only consider the technical integration, but also consider whether the production conditions support this integration. To solve the problem of production node integration in CSB, a dynamic collaboration model of production network based on cloud service bus is proposed in this paper. The model takes the capacity, cost, and production relationship of production nodes as constraints, and the overall efficiency of production network as the optimization goal. The model can calculate the new creation, modification, deletion, and other scheduling operations of production line services in real time and give the production plan with the highest resource utilization and the greatest value in the current production network. The model can improve the rationality and economy of service choreography and give full play to the value of production network. Taking an enterprise with 11 production nodes and 5 production lines as an example, this paper discusses in detail how to use this model to calculate the optimal production organization scheme and the maximum output value of the enterprise.

The Epigenetic Regulation of OLIG2 by Histone Demethylase KDM6B in Glioma Cells.

Gliomas are common tumors that occur in the brain, accounting for 80% of all malignant brain tumors. Oligodendrocyte transcription factor 2 (OLIG2) is a key transcription factor and strongly expressed in gliomas, which drives proliferation and invasion of glioma cells. Our previous studies have shown that histone lysine (K) demethylase 6B (KDM6B) promotes glioma development. The data also showed that OLIG2 content was positively correlated with KDM6B. Based on this, we proposed that KDM6B may play biological roles by regulating OLIG2 expression. Subsequently, many experiments were performed including specific inhibitor treatment, gene knockdown, and chromatin immunoprecipitation (ChIP) array. These results indicated that inhibition of KDM6B enzymatic activity with GSK-J4 reduces OLIG2 gene expression and protein content. The KDM6B knockdown experiment yielded similar results, that is, it reduces the mRNA and protein level of OLIG2 in glioma cells. ChIP assay showed that the promoter of OLIG2 can be bound by KDM6B, which catalyzes the demethylation of H3K27me3 and increases the expression of OLIG2. This study reveals a new regulatory mechanism of OLIG2 by KDM6B, which has important implications for the future development of drugs for gliomas and other neurological diseases.

Identifying unreported links between ClinicalTrials.gov trial registrations and their published results.

A substantial proportion of trial registrations are not linked to corresponding published articles, limiting analyses and new tools. Our aim was to develop a method for finding articles reporting the results of trials that are registered on ClinicalTrials.gov when they do not include metadata links. We used a set of 27,280 trial registration and article pairs to train and evaluate methods for identifying missing links in both directions-from articles to registrations and from registrations to articles. We trained a classifier with six distance metrics as feature representations to rank the correct article or registration, using recall@K to evaluate performance and compare to baseline methods. When identifying links from registrations to published articles, the classifier ranked the correct article first (recall@1) among 378,048 articles in 80.8% of evaluation cases and 34.9% in the baseline method. Recall@10 was 85.1% compared to 60.7% in the baseline. When predicting links from articles to registrations, recall@1 was 83.4% for the classifier and 39.8% in the baseline. Recall@10 was 89.5% compared to 65.8% in the baseline. The proposed method improves on our baseline document similarity method to be feasible for identifying missing links in practice. Given a ClinicalTrials.gov registration, a user checking 10 ranked articles can expect to identify the matching article in at least 85% of cases, if the trial has been published. The proposed method can be used to improve the coupling of ClinicalTrials.gov and PubMed, with applications related to automating systematic review and evidence synthesis processes.

BDNF-overexpressing MSCs delivered by hydrogel in acute ischemic stroke treatment.

Background: Ischemic stroke treatment is a challenge worldwide. The efficacy and safety of mesenchymal stem cells (MSCs) for stroke have been confirmed. However, poor survival of MSCs in the ischemic environment limits the therapy efficacy. Changes in MSC status in the ischemic environment after transplantation is difficult to monitor. This study aimed to deliver brain-derived neurotrophic factor (BDNF)-overexpressing MSCs by hydrogel (H-B-MSCs) to promote recovery after ischemic stroke. Methods: MSCs were transfected with lentivirus carrying luc2 and BDNF cassette. The properties of hydrogel were tested after synthesis with thiolated gelatin (Gel-SH), thiolated hyaluronic acid (HA-SH), and polyethylene glycol diacrylate (PEGDA). Oxygen-glucose deprivation (OGD) test was carried out to confirm the protective effects of hydrogel in the ischemic environment. Three days after stroke induction, H-B-MSCs, hydrogel carrying MSCs (H-MSCs), or phosphate-buffered saline (PBS) was injected into the brains of mice, respectively. Bioluminescence imaging (BLI) was performed at 3, 7, 14, and 21 days post-cell-transplantation to monitor the dynamic status of MSCs. In the meantime, histology, quantitative polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA), western blot, and behavior tests were carried out at different time points. Results: Hydrogel with good biocompatibility was synthesized. Lentivirus transfection significantly increased the expression of BDNF. BDNF-MSCs could be tracked by BLI in vitro. In vitro OGD/reperfusion (OGD/R) test results suggested that MSCs carried by hydrogel could survive longer in an environment with low oxygen and glucose. H-B-MSCs significantly improved functional recovery after ischemic stroke. Furthermore, H-B-MSCs treatment promoted neurogenesis, white matter recovery, and angiogenesis after ischemic stroke. MSC dynamics could be monitored in vivo with BLI. Conclusions: We effectively established a robust MSC delivery system with hydrogel. Prolonged survival of transplanted BDNF-MSCs with a hydrogel delivery system could promote the recovery of ischemic stroke via the continuous release of BDNF.