Mechanical Strain Induces and Increases Vesicular Release Monitored by Microfabricated Stretchable Electrodes.

Exocytosis involving the fusion of intracellular vesicles with cell membrane, is thought to be modulated by the mechanical cues in the microenvironment. Single-cell electrochemistry can offer unique information about the quantification and kinetics of exocytotic events, however, the effects of mechanical force on vesicular release has been poorly explored. Herein, we developed a stretchable microelectrode with excellent electrochemical stability under mechanical deformation by microfabrication of functionalized poly(3,4-ethylenedioxythiophene) conductive ink, which achieved real-time quantitation of strain-induced vesicular exocytosis from a single cell for the first time. We found that mechanical strain could cause calcium influx via the activation of Piezo1 channel in chromaffin cell, initiating the vesicular exocytosis process. Interestingly, mechanical strain increases the amount of catecholamines release by accelerating the opening and prolonging the closing of fusion pore during exocytosis. This work is expected to provide a revealing insight on the regulatory effects of mechanical stimuli on vesicular exocytosis.

Definition, risk factors, and outcome analysis of prolonged mechanical ventilation in children.

OBJECTIVE: This study aims to explore the time threshold for defining prolonged mechanical ventilation (PMV) in children, along with its risk factors and outcomes. METHODS: A prospective cohort study was conducted on children aged 29 days-18 years, who were consecutively admitted to two Pediatric Intensive Care Units (PICUs) at Children's Hospital of Chongqing Medical University, from October 2020 to June 2021. The study included patients receiving mechanical ventilation (MV) for more than 2 days (each day >6 h). Participants were divided into five groups based on the duration of MV (2-7 days, 8-14 days, 15-21 days, 21-30 days, >30 days) to compare rates of extubation failure, all-cause mortality one month post-discharge, incidence of ventilator-associated pneumonia, tracheotomy rates, total hospital stay, PICU stay, and overall hospital costs. The most clinically and statistically significant outcome variables were selected. The Youden index was used to determine the MV duration with the most significant impact on overall outcomes, defining this as PMV. Baseline characteristics, treatment information, and outcomes were compared between PMV and non-PMV groups. Univariate and multivariate logistic regression analyses were used to identify risk factors for PMV occurrence. RESULTS: A total of 382 subjects were included in the study. The distribution of children across the five MV duration groups was 44.2%, 27.7%, 10.7%, 8.9%, and 8.4% respectively. The rates of at least one extubation failure in each group were 5.9%, 10.4%, 41.5%, 41.2%, and 46.9% (p < .05). Statistically significant differences were observed among groups in terms of tracheotomy rates, all-cause mortality at 1 month postdischarge, median total hospital stay, median PICU stay, and hospital costs (p < .05). Defining PMV, the most appropriate time point calculated was 12.5 days, based on at least one extubation failure and/or death within 1 month postdischarge. Higher PIM-3 scores, weight for age <-2SD, admission for respiratory distress/insufficient ventilation and/or hemodynamic instability/shock/arrhythmia, noninvasive ventilation on the first day, and undergoing blood transfusion treatment were identified as risk factors for PMV (p < .05). CONCLUSION: In children, MV for ≥13 days significantly increases mortality rates, extubation failure and tracheotomy rates, duration of PICU and total hospital stay and costs. We suggest defining PMV as MV ≥13 days, particularly for children undergoing MV for respiratory illnesses. This definition can assist clinicians in developing appropriate treatment strategies by focusing on risk factors and providing reliable prognostic consultation to patients' families.

Callicarpayongshunensis (Lamiaceae): A new species from Hunan, China.

This study provides detailed description of a newly-discovered Callicarpayongshunensis Wen B. Xu, Xiao D. Li & Yan Ling Liu (Lamiaceae) species from Hunan, China. The species shares similarities in the inflorescence, glandular colour and leaf shape features with C.luteopunctata H. T. Chang and C.giraldii Hesse ex Rehd., while its white fruits are similar to those of C.longifolia Lamk. However, its procumbent, evergreen shrub and white fruits are distinctly different from those of C.luteopunctata and C.giraldii, while its procumbent, scarless nodes and stellate pubescence free fruits distinguishes it from C.longifolia. Images, distribution, morphological features, molecular phylogenetic classification and conservation assessment of this new Callicarpa species are explored.

Inkjet printer prediction under complicated printing conditions based on microscopic image features.

A novel technique is introduced to predict the printer model used to produce a given document. Samples containing only a few letters printed under varying conditions (i.e., different printing modes, letter types, fonts) were collected to establish a dataset of 41 inkjet printer models from common manufacturers, such as HP, Canon, and Epson. Morphological features were analyzed by extraction of image features using several algorithms in a series of microscopic images and a Wilcoxon test was used to measure the significance of variations between printed samples. Significant differences between various printing conditions might post potential challenge to questioned document examination. Discriminant analysis and the k-nearest neighbor (KNN) algorithm were also employed for source printer prediction under varying printing condition on 30% images with the rest images as training dataset. The results of a validation experiment demonstrated that while quadratic discriminant analysis (QDA) achieved an accuracy of 96.3%, a combination of KNN and QDA reached 98.6%. As such, this technique could aid in the forensic examination of printed documents.

Self-Perceptional Soft Robotics by a Dielectric Elastomer.

Soft robotics has been a rapidly growing field in recent decades due to its advantages of softness, deformability, and adaptability to various environments. However, the separation of perception and actuation in soft robot research hinders its progress toward compactness and flexibility. To address this limitation, we propose the use of a dielectric elastomer actuator (DEA), which exhibits both an actuation capability and perception stability. Specifically, we developed a DEA array to localize the 3D spatial position of objects. Subsequently, we integrate the actuation and sensing properties of DEA into soft robots to achieve self-perception. We have developed a system that integrates actuation and sensing and have proposed two modes to achieve this integration. Furthermore, we demonstrated the feasibility of this system for soft robots. When the robots detect an obstacle or an approaching object, they can swiftly respond by avoiding or escaping the obstacle. By eliminating the need for separate perception and motion considerations, self-perceptional soft robots can achieve an enhanced response performance and enable applications in a more compact and flexible field.

Real-time monitoring of intracellular biochemical response in locally stretched single cell by a nanosensor.

Mechanotransduction is the essential process that cells convert mechanical force into biochemical responses, and electrochemical sensor stands out from existing techniques by providing quantitative and real-time information about the biochemical signals during cellular mechanotransduction. However, the intracellular biochemical response evoked by mechanical force has been poorly monitored. In this paper, we report a method to apply local stretch on single cell and simultaneously monitor the ensuing intracellular biochemical signals. Specifically, a ferromagnetic micropipette was fabricated to locally stretch a single cell labeled with Fe3O4 nanoparticles under the external magnetic field, and the SiC@Pt nanowire electrode (SiC@Pt NWE) was inserted into the cell to monitor the intracellular hydrogen peroxide (H2O2) production induced by the local stretch. As a proof of concept, this work quantitatively investigated the elevated amount of H2O2 levels in single endothelial cell under different stretching amplitudes. This work puts forward a new research modality to manipulate and monitor the mechanotransduction at the single-cell level.

Chemical constituents from stipes of Lentinus edodes and their protective effects against Aß25-35-induced N9 microglia cells injury.

Nine undescribed compounds, along with eight known compounds, were isolated from the stipes of Lentinus edodes. Their structures were established by extensive spectroscopic and circular dichroism analyses. The protective effects against Aß25-35-induced N9 microglia cells injury of these compounds were tested by MTT method, and the levels of apoptosis and ROS were detected by flow cytometry. In addition, the binding sites and interactions of compound with amyloid precursor protein were revealed using molecular docking simulations. These findings further establish the structural diversity and bioactivity of stipes of L. edodes, and provide an experimental basis for targeting Alzheimer's disease as a potential strategy.

A Significant Contribution of the Classical Pathway of Complement in SARS-CoV-2 Neutralization of Convalescent and Vaccinee Sera.

Although high titers of neutralizing Abs in human serum are associated with protection from reinfection by SARS-CoV-2, there is considerable heterogeneity in human serum-neutralizing Abs against SARS-CoV-2 during convalescence between individuals. Standard human serum live virus neutralization assays require inactivation of serum/plasma prior to testing. In this study, we report that the SARS-CoV-2 neutralization titers of human convalescent sera were relatively consistent across all disease states except for severe COVID-19, which yielded significantly higher neutralization titers. Furthermore, we show that heat inactivation of human serum significantly lowered neutralization activity in a live virus SARS-CoV-2 neutralization assay. Heat inactivation of human convalescent serum was shown to inactivate complement proteins, and the contribution of complement in SARS-CoV-2 neutralization was often >50% of the neutralizing activity of human sera without heat inactivation and could account for neutralizing activity when standard titers were zero after heat inactivation. This effect was also observed in COVID-19 vaccinees and could be abolished in individuals who were undergoing treatment with therapeutic anti-complement Abs. Complement activity was mainly dependent on the classical pathway with little contributions from mannose-binding lectin and alternative pathways. Our study demonstrates the importance of the complement pathway in significantly increasing viral neutralization activity against SARS-CoV-2 in spike seropositive individuals.

ATF3/EGR1 regulates myocardial ischemia/reperfusion injury induced autophagy and inflammation in cardiomyocytes.

Myocardial ischemia/reperfusion injury (MIRI) is an irreversible adverse event during the management of coronary heart disease that lacks effective controls. The underlying mechanism of MIRI still requires further investigation. Recent studies have suggested that overexpression of ATF3 protects against MIRI by regulating inflammatory responses, ferroptosis, and autophagy. The downstream target of ATF3, EGR1, also showed cardioprotective properties against MIRI by promoting autophagy. Therefore, further investigating the effect of ATF3/EGR1 pathway on MIRI-induced inflammation and autophagy is needed. Cardiomyocyte MIRI model was established by challenging H9C2 cells with hypoxia/reoxygenation (H/R). The ATF3 overexpression-H/R cell model by transfecting ATF3 plasmid into the H9C2 cell line. The transcription levels of ATF3 and EGR1 were determined using RT-qPCR, the levels of TNF-α and IL-6 were determined using ELISA kits, the protein expression of LC3 I, LC3 II, and P62 was determined via WB, and microstructure of H9C2 cell was observed by transmission electron microscopy (TEM). Overexpression of ATF3 significantly downregulated Egr1 levels, indicating that EGR1 might be the target of ATF3. By upregulating ATF3 levels, the extracellular levels of the inflammatory cytokines TNF-α and IL-6 significantly decreased, and the protein expression of the autophagy markers LC3 I, LC3 II, and P62 significantly increased. TEM results revealed that the cell line in the H/R-ATF3 group exhibited a higher abundance of autophagosome enclosures of mitochondria. The results indicated that ATF3/EGR1 may alleviate inflammation and improve autophagy in an H/R-induced MIRI model of cardiomyocytes.

Five new eremophilane-type sesquiterpenes from the fresh roots of Rehmannia glutinosa.

Five undescribed eremophilane-type sesquiterpenes, remophilanetriols E-I (1-5), along with seven known compounds (6-12) were isolated from the fresh roots of Rehmannia glutinosa. Their structures were characterized by extensive spectroscopic data analysis and their absolute configurations were determined by comparing their calculated electronic circular dichroism (ECD) spectra and experimental ECD spectra. The anti-pulmonary fibrosis activities of all compounds were evaluated in vitro by MTT methods, and compounds 2, 8, 10, and 12 exhibited excellent anti-pulmonary fibrosis activities. In addition, compound 2 can reduce the levels of ROS and apoptosis in TGF-ß1-induced BEAS-2B cells.

Xinmailong injection on left ventricular remodeling and inflammatory mediators in patients with CHF: a systematic review and meta-analysis.

Background: Chronic heart failure (CHF) is a prevalent and highly challenging cardiovascular disease associated with high mortality rates. The occurrence and progression of CHF are closely linked to left ventricular remodeling (LVR) and inflammation. Addressing LVR and reducing inflammation can significantly slow down the progression of CHF and improve patient prognosis. Objective: To evaluate the effects of Xinmailong injection (XMLI) on LVR and inflammatory mediators in CHF patients. Method: The randomized controlled trials investigating the effectiveness of XMLI treatment for CHF were retrieved from eight databases up until 31 December 2023. To evaluate the methodological quality of included studies, the Cochrane bias risk tool was employed. Furthermore, statistical analysis, sensitivity analysis, and publication bias assessment were conducted using Stata 17.0 software. Result: Compared with conventional treatment (CT), the combination therapy of XMLI and CT significantly improved LVR and reduced inflammatory mediators, mainly manifested by an increase in LVEF (MD = 6.40, 95% CI: 5.25 to 7.55, p = 0.000), a decrease in LVEDD (MD = -4.63, 95% CI: -5.69 to -3.57, p = 0.000) and LVESD (MD = -4.00, 95% CI: -5.50 to -2.50, p = 0.000), as well as a decrease in TNF-α (MD = -7.93, 95% CI: -9.86 to -6.00, p = 0.000), IL-6 (MD = -5.25, 95% CI: -6.59 to -3.92, p = 0.000), IL-18 (MD = -36.07, 95% CI: -46.76 to -25.38, p = 0.000), CRP (MD = -4.41, 95% CI: -6.40 to -2.42, p = 0.000), hs-CRP (MD = -4.90, 95% CI: -5.71 to -4.08, p = 0.000), and an increase in IL-10 (MD = 20.19, 95% CI: 10.42 to 29.97, p = 0.000). In addition, the combination therapy showed enhanced clinical efficacy (OR = 4.08, 95% CI: 3.10 to 5.37, p = 0.000), decreased expression levels of BNP (MD = -138.48, 95% CI: -155.48 to -121.48, p = 0.000), and NT-pro BNP (MD = -315.63, 95% CI: -359.25 to -272.00, p = 0.000), and increased the 6-MWD (MD = 71.02, 95% CI: 57.23 to 84.81, p = 0.000). It is noteworthy that the combination therapy did not lead to an increase in the incidence of adverse reactions (OR = 1.01, 95% CI: 0.68 to 1.50, p = 0.97). Conclusion: This systematic review and meta-analysis demonstrated the superiority of combining XMLI and CT therapies over CT alone in improving LVR and reducing inflammatory mediators in patients with CHF. Importantly, this combination therapy does not increase adverse reactions. However, it is crucial to exercise caution while interpreting the survey results due to the limited quality of the included studies.Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=492715, Identifier CRD42023492715.

Motilin, a Novel Orexigenic Factor, Involved in Feeding Regulation in Yangtze Sturgeon (Acipenser dabryanus).

Motilin is a gastrointestinal hormone that is mainly produced in the duodenum of mammals, and it is responsible for regulating appetite. However, the role and expression of motilin are poorly understood during starvation and the weaning stage, which is of great importance in the seeding cultivation of fish. In this study, the sequences of Yangtze sturgeon (Acipenser dabryanus Motilin (AdMotilin)) motilin receptor (AdMotilinR) were cloned and characterized. The results of tissue expression showed that by contrast with mammals, AdMotilin mRNA was richly expressed in the brain, whereas AdMotilinR was highly expressed in the stomach, duodenum, and brain. Weaning from a natural diet of T. Limnodrilus to commercial feed significantly promoted the expression of AdMotilin in the brain during the period from day 1 to day 10, and after re-feeding with T. Limnodrilus the change in expression of AdMotilin was partially reversed. Similarly, it was revealed that fasting increased the expression of AdMotilin in the brain (3 h, 6 h) and duodenum (3 h), and the expression of AdMotilinR in the brain (1 h) in a time-dependent manner. Furthermore, it was observed that peripheral injection of motilin-NH2 increased food intake and the filling index of the digestive tract in the Yangtze sturgeon, which was accompanied by the changes of AdMotilinR and appetite factors expression in the brain (POMC, CART, AGRP, NPY and CCK) and stomach (CCK). These results indicate that motilin acts as an indicator of nutritional status, and also serves as a novel orexigenic factor that stimulates food intake in Acipenser dabryanus. This study lays a strong foundation for the application of motilin as a biomarker in the estimation of hunger in juvenile Acipenser dabryanu during the weaning phase, and enhances the understanding of the role of motilin as a novel regulator of feeding in fish.

Competitive Video Game Exposure Increases Aggression Through Impulsivity in Chinese Adolescents: Evidence From a Multi-Method Study.

It is widely known controversies about the results of violent video game increase aggression. However, the role of competitive video games, has received less research attention, and the underlying mechanisms of their influence are unknown. This study aimed to expand the existing literature by systematically exploring the effects of competitive video game exposure on adolescent aggression and the mediating role of impulsivity. In so doing, three types of studies (collectively N = 2919, mean age varied from 13.75 to 15.44 years, with a balanced gender) combining cross-sectional, experimental, and longitudinal approaches, were conducted. The findings consistently show that competitive video game exposure increased adolescents' aggression and impulsivity. Also, impulsivity mediated the correlation and long-term effect of competitive video game exposure on aggression. However, the experimental study did not confirm the short-term mediating effect of impulsivity, which may be related to the type of aggression measured in the study. The results indicate that competitive video game exposure is an important antecedent factor for adolescent aggression, and impulsivity is the key underlying mechanism.

Quantitative proteomics analysis reveals an important role of the transcriptional regulator UidR in the bacterial biofilm formation of Aeromonas hydrophila.

Introduction: Bacterial biofilm is a well-known characteristic that plays important roles in diverse physiological functions, whereas the current intrinsic regulatory mechanism of its formation is still largely unknown. Methods: In the present study, a label-free based quantitative proteomics technology was conducted to compare the differentially expressed proteins (DEPs) between ΔuidR and the wild-type strain in the biofilm state. Results: The results showed that the deletion of gene uidR encoding a TetR transcriptional regulator significantly increased the biofilm formation in Aeromonas hydrophila. And there was a total of 220 DEPs, including 120 up-regulated proteins and 100 down-regulated proteins between ΔuidR and the wild-type strain based on the quantitative proteomics. Bioinformatics analysis suggested that uidR may affect bacterial biofilm formation by regulating some related proteins in glyoxylic acid and dicarboxylic acid pathway. The expressions of selected proteins involved in this pathway were further confirmed by q-PCR assay, and the results was in accordance with the quantitative proteomics data. Moreover, the deletion of four genes (AHA_3063, AHA_3062, AHA_4140 and aceB) related to the glyoxylic acid and dicarboxylic acid pathway lead to a significant decrease in the biofilm formation. Discussion: Thus, the results indicated that uidR involved in the regulatory of bacterial biofilm formation, and it may provide a potential target for the drug development and a new clue for the prevention of pathogenic A. hydrophila in the future.

Serum PYCARD may become a new diagnostic marker for rheumatoid arthritis patients.

BACKGROUND: The objective of this investigation is to analyze the levels and clinical relevance of serum PYCARD (Pyrin and CARD domain-containing protein, commonly known as ASC-apoptosis-associated speck-like protein containing a caspase activation and recruitment domain), interleukin-38 (IL-38), and interleukin-6 (IL-6) in individuals afflicted with rheumatoid arthritis (RA). METHODS: Our study comprised 88 individuals diagnosed with RA who sought medical attention at the Affiliated Hospital of Chengde Medical University during the period spanning November 2021 to June 2023, constituting the test group. Additionally, a control group of 88 individuals who underwent health assessments at the same hospital during the aforementioned timeframe was included for comparative purposes. The study involved the assessment of IL-38, IL-6, PYCARD, anti-cyclic citrullinated peptide antibody (anti-CCP), and erythrocyte sedimentation rate (ESR) levels in both groups. The research aimed to explore the correlations and diagnostic efficacy of these markers, employing pertinent statistical analyses for comprehensive evaluation. RESULTS: The test group had higher expression levels of PYCARD, IL-6, and IL-38 than the control group (P < 0.05). Based on the correlation analysis, there was a strong relationship between PYCARD and IL-38 (P < 0.01). The receiver operating characteristic (ROC) curve analysis revealed area under the curve (AUC) values of 0.97, 0.96, and 0.96 when using combinations of PYCARD and anti-CCP, IL-38 and anti-CCP, and IL-6 and anti-CCP for predicting RA, respectively. Importantly, all three of these pairs demonstrated superior AUC values compared to PYCARD, IL-38, IL-6, ESR, or anti-CCP used as standalone diagnostic indicators. CONCLUSION: PYCARD, IL-6, and IL-38 exhibit promising potential as novel diagnostic markers and may constitute valuable tools for supporting the diagnosis of RA.

The Effects of Family and School Interpersonal Relationships on Depression in Chinese Elementary School Children: The Mediating Role of Academic Stress and the Moderating Role of Self-Esteem.

This study explores the relative contributions and psychological mechanisms of the effects of family (father-child and mother-child) and school (teacher-student and student-student) interpersonal relationships on depression in elementary school children. The participants (n = 20,629) were elementary school children (48.19% male) aged nine to 13 years from Southwest China during the COVID-19 pandemic. They voluntarily completed questionnaires regarding parent-child, teacher-student, and student-student relationships, as well as academic stress and self-esteem. The results indicate that the effect of family interpersonal relationships on children's depression was stronger than that of school interpersonal relationships. The predictive effects of father-child and mother-child relationships on children's depression did not significantly differ; however, the effect of student-student relationships was significantly stronger than that of teacher-student relationships. Academic stress partially mediated the effect of interpersonal relationships on depression in elementary school children. The effects of family interpersonal relationships and academic stress on depression were moderated by self-esteem. These findings underscore the disparities and mechanisms pertaining to the impacts of diverse interpersonal associations on children's depression, thus signifying significant implications for the advancement of research and intervention strategies aimed at addressing this issue.

Polystyrene microplastic-induced endoplasmic reticulum stress contributes to growth plate endochondral ossification disorder in young rat.

BACKGROUND: Previous studies on the effects of microplastics (MPs) on bone in early development are limited. This study aimed to investigate the adverse effects of MPs on bone in young rats and the potential mechanism. METHODS: Three-week-old female rats were orally administered MPs for 28 days, and endoplasmic reticulum (ER) stress inhibitor salubrinal (SAL) and ER stress agonist tunicamycin (TM) were added to evaluate the effect of ER stress on toxicity of MPs. The indicators of growth and plasma markers of bone turnover were evaluated. Tibias were analyzed using micro-computed tomography (micro-CT). Histomorphological staining of growth plates was performed, and related gene expression of growth plate chondrocytes was tested. RESULTS: After exposure of MPs, the rats had decreased growth, shortened tibial length, and altered blood calcium and phosphorus metabolism. Trabecular bone was sparse according to micro-CT inspection. In the growth plate, the thickness of proliferative zone substantial reduced while the thickness of hypertrophic zone increased significantly, and the chondrocytes were scarce and irregularly arranged according to tibial histological staining. The transcription of the ER stress-related genes BIP, PERK, ATF4, and CHOP dramatically increased, and the transcription factors involved in chondrocyte proliferation, differentiation, apoptosis, and matrix secretion were aberrant according to RT-qPCR and western blotting. Moreover, the addition of TM showed higher percentage of chondrocyte death. Administration of SAL alleviated all of the MPs-induced symptoms. CONCLUSION: These results indicated that MPs could induce growth retardation and longitudinal bone damage in early development. The toxicity of MPs may attribute to induced ER stress and impaired essential processes of the endochondral ossification after MPs exposure.

An ultrasound-triggered injectable sodium alginate scaffold loaded with electrospun microspheres for on-demand drug delivery to accelerate bone defect regeneration.

Biological processes, such as bone defects healing are precisely controlled in both time and space. This spatiotemporal characteristic inspires novel therapeutic strategies. The sustained-release systems including hydrogels are commonly utilized in the treatment of bone defect; however, traditional hydrogels often release drugs at a consistent rate, lacking temporal precision. In this study, a hybrid hydrogel has been developed by using sodium alginate, sucrose acetate isobutyrate, and electrospray microspheres as the base materials, and designed with ultrasound response, and on-demand release properties. Sucrose acetate isobutyrate was added to the hybrid hydrogel to prevent burst release. The network structure of the hybrid hydrogel is formed by the interconnection of Ca2+ with the carboxyl groups of sodium alginate. Notably, when the hybrid hydrogel is exposed to ultrasound, the ionic bond can be broken to promote drug release; when ultrasound is turned off, the release returned to a low-release state. This hybrid hydrogel reveals not only injectability, degradability, and good mechanical properties but also shows multiple responses to ultrasound. And it has good biocompatibility and promotes osteogenesis efficiency in vivo. Thus, this hybrid hydrogel provides a promising therapeutic strategy for the treatment of bone defects.

DAE-CFR: detecting microRNA-disease associations using deep autoencoder and combined feature representation.

BACKGROUND: MicroRNA (miRNA) has been shown to play a key role in the occurrence and progression of diseases, making uncovering miRNA-disease associations vital for disease prevention and therapy. However, traditional laboratory methods for detecting these associations are slow, strenuous, expensive, and uncertain. Although numerous advanced algorithms have emerged, it is still a challenge to develop more effective methods to explore underlying miRNA-disease associations. RESULTS: In the study, we designed a novel approach on the basis of deep autoencoder and combined feature representation (DAE-CFR) to predict possible miRNA-disease associations. We began by creating integrated similarity matrices of miRNAs and diseases, performing a logistic function transformation, balancing positive and negative samples with k-means clustering, and constructing training samples. Then, deep autoencoder was used to extract low-dimensional feature from two kinds of feature representations for miRNAs and diseases, namely, original association information-based and similarity information-based. Next, we combined the resulting features for each miRNA-disease pair and used a logistic regression (LR) classifier to infer all unknown miRNA-disease interactions. Under five and tenfold cross-validation (CV) frameworks, DAE-CFR not only outperformed six popular algorithms and nine classifiers, but also demonstrated superior performance on an additional dataset. Furthermore, case studies on three diseases (myocardial infarction, hypertension and stroke) confirmed the validity of DAE-CFR in practice. CONCLUSIONS: DAE-CFR achieved outstanding performance in predicting miRNA-disease associations and can provide evidence to inform biological experiments and clinical therapy.

Thermal ablation for multifocal papillary thyroid microcarcinoma: a systematic review and meta-analysis.

BACKGROUND: Clinical studies have indicated the potential safety and efficacy of thermal ablation (TA) in treating multifocal papillary thyroid microcarcinoma (MPTMC). However, a comprehensive systematic evaluation of its effectiveness was still lack. METHODS: PubMed, EMBASE and Cochrane Library databases were systematically searched for studies published until October 23, 2023, that reported on the effectiveness of thermal ablation in the management of MPTMC. Data extraction and methodological quality assessment were independently conducted by two reviewers following the guidelines outlined in the PRISMA. RESULTS: This systematic review and meta-analysis identified 389 tumors in 169 patients from four studies. After treatment with different TA, the combined rate of complete disappearance of MPTMC was 92.8% [95% confidence interval (CI): 68.2-100] and the combined rate of overall complications was 4.4% [95% CI: 1.5-8.5]. During the follow-up period, local tumor recurrence was observed in only 2 patients with a combined rate of 0.2% [95% CI: 0.0-2.6]; lymph node metastasis (LNM) was observed in 3 patients with a combined rate of 1.2% [95% CI: 0-4.1]. Additionally, 6 patients developed new PTMC. It is noteworthy that no patients were observed to develop distant metastases during the follow-up period, and no patients had delayed surgery after underwent ablation. CONCLUSIONS: For patients grappling with MPTMC, TA emerges as an excellent approach for achieving localized tumor control. Nonetheless, achieving favorable outcomes necessitates stringent inclusion criteria and a profound level of expertize.