Radiation-Synthesized Metal-Organic Frameworks with Ligand-Induced Lewis Pairs for Selective CO2 Electroreduction.

The electrochemical activation of inert CO2 molecules through C─C coupling reactions under ambient conditions remains a significant challenge but holds great promise for sustainable development and the reduction of CO2 emission. Lewis pairs can capture and react with CO2, offering a novel strategy for the electrosynthesis of high-value-added C2 products. Herein, an electron-beam irradiation strategy is presented for rapidly synthesizing a metal-organic framework (MOF) with well-defined Lewis pairs (i.e., Cu- Npyridinic). The synthesized MOFs exhibit a total C2 product faradic efficiency of 70.0% at -0.88 V versus RHE. In situ attenuated total reflection Fourier transform infrared and Raman spectra reveal that the electron-deficient Lewis acidic Cu sites and electron-rich Lewis basic pyridinic N sites in the ligand facilitate the targeted chemisorption, activation, and conversion of CO2 molecules. DFT calculations further elucidate the electronic interactions of key intermediates in the CO2 reduction reaction. The work not only advances Lewis pair-site MOFs as a new platform for CO2 electrochemical conversion, but also provides pioneering insights into the underlying mechanisms of electron-beam irradiated synthesis of advanced nanomaterials.

Direct Comparative Studies Revealing the Contribution of TADF Activity of Organic Emitters Towards Efficient Electrochemiluminescence.

Electrochemiluminescence (ECL) featuring thermally activated delayed fluorescence (TADF) properties has attracted considerable interest, showcasing their potential for 100 % exciton harvesting, which marks a significant advancement in the realm of organic ECL. However, the challenge of elucidating the precise contribution of TADF to the enhanced ECL efficiency arises due to the lack of comparative studies of organic compounds with or without efficient TADF properties. In this study, we present four carbazole-benzonitrile molecules possessing similar chemical structures and comparable exchange energy (ΔEST). Despite their comparable properties, these compounds exhibited varying TADF efficiencies, warranting a closer examination of their underlying structural and electronic characteristics governing the optical properties. Consequently, intense ECL emission was only observed from 4CzBN with a remarkable TADF efficiency, underscoring the substantial difference in the ECL signal among molecules with comparable ΔEST and similar spectral properties but varying TADF activity.

Deep learning-based classification model for GPR151 activator activity prediction.

BACKGROUND: GPR151 is a kind of protein belonging to G protein-coupled receptor family that is closely associated with a variety of physiological and pathological processes.The potential use of GPR151 as a therapeutic target for the management of metabolic disorders has been demonstrated in several studies, highlighting the demand to explore its activators further. Activity prediction serves as a vital preliminary step in drug discovery, which is both costly and time-consuming. Thus, the development of reliable activity classification model has become an essential way in the process of drug discovery, aiming to enhance the efficiency of virtual screening. RESULTS: We propose a learning-based method based on feature extractor and deep neural network to predict the activity of GPR151 activators. We first introduce a new molecular feature extraction algorithm which utilizes the idea of bag-of-words model in natural language to densify the sparse fingerprint vector. Mol2vec method is also used to extract diverse features. Then, we construct three classical feature selection algorithms and three types of deep learning model to enhance the representational capacity of molecules and predict activity label by five different classifiers. We conduct experiments using our own dataset of GPR151 activators. The results demonstrate high classification accuracy and stability, with the optimal model Mol2vec-CNN significantly improving performance across multiple classifiers. The svm classifier achieves the best accuracy of 0.92 and F1 score of 0.76 which indicates promising applications for our method in the field of activity prediction. CONCLUSION: The results suggest that the experimental design of this study is appropriate and well-conceived. The deep learning-based feature extraction algorithm established in this study outperforms traditional feature selection algorithm for activity prediction. The model developed can be effectively utilized in the pre-screening stage of drug virtual screening.

Machine-learning assisted scheduling optimization and its application in quantum chemical calculations.

Easy and effective usage of computational resources is crucial for scientific calculations, both from the perspectives of timeliness and economic efficiency. This work proposes a bi-level optimization framework to optimize the computational sequences. Machine-learning (ML) assisted static load-balancing, and different dynamic load-balancing algorithms can be integrated. Consequently, the computational and scheduling engine of the ParaEngine is developed to invoke optimized quantum chemical (QC) calculations. Illustrated benchmark calculations include high-throughput drug suit, solvent model, P38 protein, and SARS-CoV-2 systems. The results show that the usage rate of given computational resources for high throughput and large-scale fragmentation QC calculations can primarily profit, and faster accomplishing computational tasks can be expected when employing high-performance computing (HPC) clusters.

Association of inactivated COVID-19 vaccination with maternal coagulation function in early pregnancy.

Reports of rare but severe thrombotic events after receiving some COVID-19 vaccines brought concerns for the possibility of vaccine-induced coagulation abnormality. However, no study has reported the impacts of COVID-19 vaccination on coagulation function in pregnant women. We aimed to explore whether vaccination with inactivated COVID-19 vaccines before pregnancy was associated with coagulation changes in pregnant women. We conducted a retrospective cohort study in a tertiary-care hospital in Shanghai, China. A total of 5166 pregnant women were included, of whom 2721 (52.7%) completed vaccination before conception. Compared with unvaccinated women, the mean serum levels of prothrombin time (PT) and fibrinogen (FIB) were lower in vaccinated women by 0.09 (ß = -0.09, 95% confidence interval [CI], -0.13, -0.05) mg/L and 0.11 (ß = -0.11, 95% CI, -0.15, -0.07) mg/L, and the mean D-Dimer (D-D) levels were higher by 0.12 (ß = 0.12, 95% CI, 0.09, 0.15) mg/L. However, no significant association was observed between COVID-19 vaccination and serum levels of activated partial thromboplastin time (APTT), fibrinogen degradation product (FDP) or thrombin time (TT). Our findings suggested that inactivated COVID-19 vaccination before conception resulted in a small change in maternal coagulation function, but this might not have clinical significance.

Research on the Relative Position Detection Method between Orchard Robots and Fruit Tree Rows.

The relative position of the orchard robot to the rows of fruit trees is an important parameter for achieving autonomous navigation. The current methods for estimating the position parameters between rows of orchard robots obtain low parameter accuracy. To address this problem, this paper proposes a machine vision-based method for detecting the relative position of orchard robots and fruit tree rows. First, the fruit tree trunk is identified based on the improved YOLOv4 model; second, the camera coordinates of the tree trunk are calculated using the principle of binocular camera triangulation, and the ground projection coordinates of the tree trunk are obtained through coordinate conversion; finally, the midpoints of the projection coordinates of different sides are combined, the navigation path is obtained by linear fitting with the least squares method, and the position parameters of the orchard robot are obtained through calculation. The experimental results show that the average accuracy and average recall rate of the improved YOLOv4 model for fruit tree trunk detection are 5.92% and 7.91% higher, respectively, than those of the original YOLOv4 model. The average errors of heading angle and lateral deviation estimates obtained based on the method in this paper are 0.57° and 0.02 m. The method can accurately calculate heading angle and lateral deviation values at different positions between rows and provide a reference for the autonomous visual navigation of orchard robots.

Effect of particle sizes of biochar on CO2 emissions in a poplar plantation of ancient Yellow River channel, China.

Forest soil is a vital pool of organic carbon, which is sensitive to management. Biochar addition could change the CO2 emissions from soil, but its effects are still ambiguous. Moreover, the impacts of particle sizes of biochar on CO2 emissions are still unknown. In this study, a series of field experiments were conducted to investigate the effects of biochar addition on CO2 emissions in a poplar plantation (Populus nigra), China. Biochar with two application rates of (10 and 50 t/ha) and three particle sizes (3-1 mm, 1-0.1 mm, and <0.1 mm) was applied into the surface soil (0-10 cm), and the soil without biochar was set as control. The results showed that a high level of fine biochar addition (1-0.1 mm and <0.1 mm) had similar and positive effects on CO2 emissions by increasing the contents of soil ammonium, available phosphorus, easily oxidizable carbon, soil moisture, soil capillary pore, and the activity of ß-glucosidase. However, biochar addition (1-0.1 mm and <0.1 mm) reduced the bioavailability of dissolved organic carbon (DOC), producing a negative relationship between DOC content and CO2 emissions. This investigation highlights the importance of biochar with different particle sizes in adjusting CO2 emissions from temperate soils.

Di(arylcarbazole) Substituted Oxetanes as Efficient Hole Transporting Materials with High Thermal and Morphological Stability for OLEDs.

A group of di(arylcarbazole)-substituted oxetanes has been prepared in Suzuki reactions by using the key starting material 3,3-di[3-iodocarbazol-9-yl]methyloxetane and various boronic acids (fluorophenylboronic acid, phenylboronic acid or naphthalene-1-boronic acid). Full characterization of their structure has been presented. The low molar mass compounds represent materials having high thermal stability with 5% mass loss thermal degradation temperatures in the range of 371-391 °C. Glass transition temperatures of the materials are also very high and range from 107 °C to 142 °C, which is a big advantage for formation of stable amorphous layers for optoelectronic devices, i.e., organic light emitting diodes. Hole transporting properties of the prepared materials were confirmed in formed organic light emitting diodes with tris(quinolin-8-olato)aluminium (Alq3) as a green emitter, which also served as an electron transporting layer. In the device's materials, 3,3-di[3-phenylcarbazol-9-yl]methyloxetane (5) and 3,3-di[3-(1-naphthyl)carbazol-9-yl]methyloxetane (6) demonstrated superior hole transporting properties than that of material 3,3-di[3-(4-flourophenyl)carbazol-9-yl]methyloxetane (4) based device. When material 5 was used in the device structure, the OLED demonstrated rather low turn-on voltage of 3.7 V, luminous efficiency of 4.2 cd/A, power efficiency of 2.6 lm/W and maximal brightness exceeding 11670 cd/m2. HTL of 6 based device also showed exclusive OLED characteristics. The device was characterized by turn-on voltage of 3.4 V, maximum brightness of 13193 cd/m2, luminous efficiency of 3.8 cd/A and power efficiency of 2.6 lm/W. An additional hole injecting-transporting layer (HI-TL) of PEDOT considerably improved functions of the device with HTL of compound 4. The modified OLED with a layer of the derivative 4 demonstrated exclusive characteristics with turn-on voltage of 3.9 V, high luminous efficiency of 4.7 cd/A, power efficiency of 2.6 lm/W and maximal brightness exceeding 21,000 cd/m2. These observations confirmed that the prepared materials have a big potential in the field of optoelectronics.

Superhydrophobic Functionalized Ti3C2Tx MXene-Based Skin-Attachable and Wearable Electrochemical pH Sensor for Real-Time Sweat Detection.

Sweat pH is a critical indicator for evaluating human health. With the extensive attention on the wearable and flexible biosensing devices, the technology for the monitoring of human sweat can be realized. In this study, a sensitive, miniaturized, and flexible electrochemical sweat pH sensor was developed for the continuous and real-time monitoring of the hydrogen-ion concentration in human sweat. A flexible electrode was fabricated on the poly(ethylene terephthalate) (PET) substrate by a simple and low-cost screen-printing technology, which was based on the integration of fluoroalkyl silane-functionalized Ti3C2Tx (F-Ti3C2Tx) and the polyaniline (PANI) membrane technology instead of the traditional ion-sensitive membrane. The surface functionalization strategy for Ti3C2Tx with perfluorodecyltrichlorosilane can provide environmental stability. Functionalized Ti3C2Tx (F-Ti3C2Tx) was doped with PANI to obtain improved responsiveness, sensitivity, and reversibility. The constructed microsize, portable, and wearable F-Ti3C2Tx/PANI pH sensor aimed to real-time monitor the pH value of human sweat during exercise. On-body sweat pH monitoring for females and males, respectively, exhibited high accuracy and continuous stability compared with ex situ analyses. This study thus offers a facile and practical solution for developing a highly reliable MXene-based mini-type pH sensor to realize the online monitoring of human sweat pH.

Global divergent trends of algal blooms detected by satellite during 1982-2018.

Algal blooms (ABs) in inland lakes have caused adverse ecological effects, and health impairment of animals and humans. We used archived Landsat images to examine ABs in lakes (>1 km2 ) around the globe over a 37-year time span (1982-2018). Out of the 176032 lakes with area >1 km2 detected globally, 863 were impacted by ABs, 708 had sufficiently long records to define a trend, and 66% exhibited increasing trends in frequency ratio (FRQR, ratio of the number of ABs events observed in a year in a given lake to the number of available Landsat images for that lake) or area ratio (AR, ratio of annual maximum area covered by ABs observed in a lake to the surface area of that lake), while 34% showed a decreasing trend. Across North America, an intensification of ABs severity was observed for FRQR (p < .01) and AR (p < .01) before 1999, followed by a decrease in ABs FRQR (p < .01) and AR (p < .05) after the 2000s. The strongest intensification of ABs was observed in Asia, followed by South America, Africa, and Europe. No clear trend was detected for the Oceania. Across climatic zones, the contributions of anthropogenic factors to ABs intensification (16.5% for fertilizer, 19.4% for gross domestic product, and 18.7% for population) were slightly stronger than climatic drivers (10.1% for temperature, 11.7% for wind speed, 16.8% for pressure, and for 11.6% for rainfall). Collectively, these divergent trends indicate that consideration of anthropogenic factors as well as climate change should be at the forefront of management policies aimed at reducing the severity and frequency of ABs in inland waters.

A scaffold of thermally activated delayed fluorescent polymer dots towards aqueous electrochemiluminescence and biosensing applications.

To achieve the most efficient, all-exciton-harvesting organic electrochemiluminescence (ECL) for biosensing, aqueous thermally activated delayed fluorescence (TADF)-ECL (aqueous TADF-ECL) was successfully launched to provide a breakthrough for the theoretical ECL efficiency limitation of aqueous fluorescence ECL (aqueous FL-ECL). However, achieving efficient TADF emitters suitable for aqueous TADF-ECL remains challenging. A previous strategy relied on TADF small molecular nanoparticles (NPs). However, the aggregation caused quenching of such TADF molecules within NPs is intense, which renders such NPs inefficient for ECL emission. Herein, we propose developing conjugated polymer dots (Pdots) based aqueous TADF-ECL. Compared to the intrinsic TADF polymer, the Pdots achieve a comparable TADF photophysical properties in water, i.e., the comparable PL spectra, similar PL quantum efficiency (ΦPL) and intense delayed fluorescent contributions via a fast reverse intersystem crossing rate (kRISC) of 1.5 × 106 s-1. The resultant relative ECL efficiency (ΦECL) of the oxidative-reduction ECL system (C2O42- as the co-reactant) is as high as 11.73% (vs. the Ru(bpy)32+ counterpart). Additionally, satisfactory dopamine biosensing was accomplished for such TADF-Pdots/C2O42- couple. All those results are combined to highlight the promising potential of such an aqueous TADF-ECL strategy.

Ultrasonography in the assessment of primary myxofibrosarcoma in the left atrium: a case report.

BACKGROUND: Cardiac myxofibrosarcoma is a rare cardiac malignant tumor, whose diagnosis is challenging due to its rare and non-specific manifestations. Ultrasound is the most important tool for detecting cardiac tumors. Yet, its diagnostic value in cardiac myxoidfibrosarcoma is rarely reported. Herein, we summarized the ultrasonic manifestations of myxofibrosarcoma in a 72-year-old Han woman. CASE PRESENTATION: The patient presented with crushing chest pain without obvious inducement, lasting 3-5 min each time, which would be relieved after rest, accompanied by palpitation, chest tightness, shortness of breath, dizziness, and syncope. The electrocardiogram (ECG) suggested atrial fibrillation. Ultrasound found two moderate echogenic masses in the left atrium; one was about 48 × 31 mm in size, and the other was about 25 × 24 mm in size. The clinical diagnosis was atrial mass and atrial fibrillation. The patient underwent the operation of left atrial tumor resection + mitral valvuloplasty + atrial fibrillation radiofrequency ablation + left atrial appendectomy. The tumor was completely removed, and the patient did not receive radiotherapy or chemotherapy after surgery. The patient was reexamined by ultrasound at 6, 42, and 91 days after surgery, and no obvious abnormalities were found. On day 115, moderate echoic mass was detected on the posterior wall of the left atrium, nearing the mitral valve ring, with a size of about 28 × 23 mm. Currently, the patient is under follow-up care. CONCLUSION: As the most important examination method for cardiac tumors, cardiac ultrasound has good diagnostic and differential diagnosis value and can be used regularly due to its simplicity and safety. The diagnosis rate of cardiac myxofibrosarcoma can be greatly improved by summarizing the ultrasonographic manifestations of cardiac myxofibrosarcoma and differentiating them from other lesions.

5,10-Methylenetetrahydrofolate reductase becomes phosphorylated during meiotic maturation in mouse oocytes.

The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) links the folate cycle that produces one-carbon units with the methionine cycle that converts these into S-adenosylmethionine (SAM), the universal methyl donor for almost all methyltransferases. Previously, MTHFR has been shown to be regulated by phosphorylation, which suppresses its activity. SAM levels have been shown to increase substantially soon after initiation of meiotic maturation of the mouse germinal vesicle (GV) stage oocyte and then decrease back to their original low level in mature second meiotic metaphase (MII) eggs. As MTHFR controls the entry of one-carbon units into the methionine cycle, it is a candidate regulator of the SAM levels in oocytes and eggs. Mthfr transcripts are expressed in mouse oocytes and preimplantation embryos and MTHFR protein is present at each stage. In mature MII eggs, the apparent molecular weight of MTHFR was increased compared with GV oocytes, which we hypothesized was due to increased phosphorylation. The increase in apparent molecular weight was reversed by treatment with lambda protein phosphatase (LPP), indicating that MTHFR is phosphorylated in MII eggs. In contrast, LPP had no effect on MTHFR from GV oocytes, 2-cell embryos, or blastocysts. MTHFR was progressively phosphorylated after initiation of meiotic maturation, reaching maximal levels in MII eggs before decreasing again after egg activation. As phosphorylation suppresses MTHFR activity, it is predicted that MTHFR becomes inactive during meiotic maturation and is minimally active in MII eggs, which is consistent with the reported changes in SAM levels during mouse oocyte maturation.

Circ_0067934 reduces JNK phosphorylation through a microRNA-545-3p/PPA1 axis to enhance tumorigenesis and cisplatin resistance in ovarian cancer.

BACKGROUND: Circular RNA 0067934 (circ_0067934) has been revealed as a cancer driver in multiple human malignancies, whereas its action in the pathogenesis of ovarian cancer (OC) remains unclear. This study focuses on the function of circ_0067934 in tumorigenesis and cisplatin (DDP) resistance in OC and the molecular mechanism. METHODS: Expression of circ_0067934 in OC tissues and cells was examined, and its correlation with the clinical characteristics of patients was analyzed. Candidate targets of circ_0067934 were predicted using bioinformatics systems. Binding relationships between circ_0067934 and microRNA (miR)-545-3p and between miR-545-3p and inorganic pyrophosphatase 1 (PPA1) were validated via luciferase assays. Gain- and loss-of functions of circ_0067934, miR-545-3p and PPA1 were performed to determine their functions in proliferation, invasion, apoptosis and DDP resistance of OC cells in vitro and in vivo. RESULTS: Circ_0067934 was overexpressed in OC samples and associated with advanced tumor staging and lymph node metastasis. Downregulation of circ_0067934 reduced DDP resistance of the DDP-resistant A2780/DDP cell line and reduced cell proliferation and invasion, but the malignant behaviors of OC cells were restored after further miR-545-3p downregulation. Circ_0067934 served as a sponge for miR-545-3p and diminished its suppressive effect on PPA1 translation. Artificial upregulation of PPA1 enhanced proliferation, invasion and DDP resistance of A2780/DDP cells, and it reduced phosphorylation of the pro-apoptotic JNK signaling. Similar results were found in vivo. CONCLUSION: This study suggests that circ_0067934 sequesters miR-545-3p and enhances PPA1 expression to promote tumorigenesis and DDP resistance in OC. This study may provide novel approaches in the management of OC.

Human Grasp Mechanism Understanding, Human-Inspired Grasp Control and Robotic Grasping Planning for Agricultural Robots.

As the end execution tool of agricultural robots, the manipulator directly determines whether the grasping task can be successfully completed. The human hand can adapt to various objects and achieve stable grasping, which is the highest goal for manipulator design and development. Thus, this study combines a multi-sensor fusion tactile glove to simulate manual grasping, explores the mechanism and characteristics of the human hand, and formulates rational grasping plans. According to the shape and size of fruits and vegetables, the grasping gesture library is summarized to facilitate the matching of optimal grasping gestures. By analyzing inter-finger curvature correlations and inter-joint pressure correlations, we investigated the synergistic motion characteristics of the human hand. In addition, the force data were processed by the wavelet transform algorithms and then the thresholds for sliding detection were set to ensure robust grasping. The acceleration law under the interaction with the external environment during grasping was also discussed, including stable movement, accidental collision, and placement of the target position. Finally, according to the analysis and summary of the manual gripping mechanism, the corresponding pre-gripping planning was designed to provide theoretical guidance and ideas for the gripping of robots.

Studies on Annihilation and Coreactant Electrochemiluminescence of Thermally Activated Delayed Fluorescent Molecules in Organic Medium.

Very recently, there is a great research interest in electrochemiluminescence (ECL) featuring thermally activated delayed fluorescence (TADF) properties, i.e., TADF-ECL. It is appealing since the earlier reports in this topic well-confirmed that this strategy has a great potential in achieving all-exciton-harvesting ECL efficiency under electrochemical excitation, which is a breakthrough in the topic of organic ECL. However, organic phase electrochemistry and ECL studies surrounding TADF-ECL are still extremely rare. Especially, the ECL spectra of previous reported TADF emitters are still very different from their PL spectra. In this work, we systematically measure and discuss the liquid electrochemistry and ECL behavior of two typical TADF molecules in organic medium. Most importantly, we verify for the first time that the ECL spectra of them (coreactant ECL mode) are identical to their PL spectra counterparts, which confirms the effectiveness of TADF photophysical properties in the coreactant ECL mode in practice.

Alterations of actin cytoskeleton and arterial protein level in patients with obstructive jaundice.

Vascular hypo-responsiveness to vasopressors in patients with obstructive jaundice (OJ) is a common anesthetic event, which leads to perioperative complications and increased mortality. The cause of this clinical issue remains unclear. In this study, we estimated the actin cytoskeleton and arterial protein level in the artery of OJ patients by proteomic analysis. Ten patients with OJ due to bile duct diseases or pancreatic head carcinoma were enrolled, while another ten non-jaundice patients with chronic cholecystitis or liver hemangioma as the control group. Vascular reactivity to noradrenaline was measured before anesthesia on the day of surgery. Artery samples in adjacent tissues of removed tumor were collected and evaluated by 2-dimensional electrophoresis. Proteins with differential expression were detected by MALDI-TOF mass spectrometry with immunoblot confirmation. The results confirmed the phenomenon of vascular hypo-reactivity in OJ patients as suppressed aortic response to noradrenaline were existed in these patients. We also found that actin cytoskeleton and several actin-binding proteins were up- or down-regulated in the artery of OJ patients. These proteins changed in OJ patents might be the basic mechanism of vascular hypo-reactivity, further studies to uncover the role of these proteins in OJ is critical for clinical treatment of these patients.

Single-Atom Electrocatalysts for Multi-Electron Reduction of CO2.

The multi-electron reduction of CO2 to hydrocarbons or alcohols is highly attractive in a sustainable energy economy, and the rational design of electrocatalysts is vital to achieve these reactions efficiently. Single-atom electrocatalysts are promising candidates due to their well-defined coordination configurations and unique electronic structures, which are critical for delivering high activity and selectivity and may accelerate the explorations of the activity origin at atomic level as well. Although much effort has been devoted to multi-electron reduction of CO2 on single-atom electrocatalysts, there are still no reviews focusing on this emerging field and constructive perspectives are also urgent to be addressed. Herein recent advances in how to design efficient single-atom electrocatalysts for multi-electron reduction of CO2 , with emphasis on strategies in regulating the interactions between active sites and key reaction intermediates, are summarized. Such interactions are crucial in designing active sites for optimizing the multi-electron reduction steps and maximizing the catalytic performance. Different design strategies including regulation of metal centers, single-atom alloys, non-metal single-atom catalysts, and tandem catalysts, are discussed accordingly. Finally, current challenges and future opportunities for deep electroreduction of CO2 are proposed.

A Noncoding Regulatory RNAs Network Driven by Circ-CDYL Acts Specifically in the Early Stages Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the fastest-rising causes of cancer-related death worldwide, but its deficiency of specific biomarkers and therapeutic targets in the early stages lead to severe inadequacy in the early diagnosis and treatment of HCC. Covalently closed circular RNA (circRNA), which was once considered an aberrant splicing by-product, is now drawing new interest in cancer research because of its remarkable functionality. Beneath the surface of the dominant functional proteins events, a hidden circRNA-centric noncoding regulatory RNAs network active in the very early stage of HCC is here revealed by a genome-wide analysis of mRNA, circRNA, and microRNA (miRNA) expression profiles. Circ-CDYL (chromodomain Y like) is specifically up-regulated in the early stages of HCC and therefore contributes to the properties of epithelial cell adhesion molecule (EPCAM)-positive liver tumor-initiating cells. Circ-CDYL interacts with mRNAs encoding hepatoma-derived growth factor (HDGF) and hypoxia-inducible factor asparagine hydroxylase (HIF1AN) by acting as the sponge of miR-892a and miR-328-3p, respectively. Subsequently, activation of the phosphoinositide 3-kinase (PI3K)-AKT serine/threonine kinase-mechanistic target of rapamycin kinase complex 1/ß-catenin and NOTCH2 pathways, which promote the expression of the effect proteins, baculoviral IAP repeat containing 5 (BIRC5 or SURVIVIN) and MYC proto-oncogene, is influenced by circ-CDYL. A treatment incorporating circ-CDYL interference and traditional enzyme inhibitors targeting PI3K and HIF1AN demonstrated highly effective inhibition of stem-like characteristics and tumor growth in HCC. Finally, we demonstrated that circ-CDYL expression or which combined with HDGF and HIF1AN are both independent markers for discrimination of early stages of HCC with the odds ratios of 1.09 (95% confidence interval [CI], 1.02-1.17) and 124.58 (95% CI, 13.26-1170.56), respectively. Conclusion: These findings uncover a circRNA-centric noncoding regulatory RNAs network in the early stages of HCC and thus provide a possibility for surveillance and early treatment of HCC.

Preoperative Estimated Risk of Microvascular Invasion is Associated with Prognostic Differences Following Liver Resection Versus Radiofrequency Ablation for Early Hepatitis B Virus-Related Hepatocellular Carcinoma.

OBJECTIVES: The aim of this study was to examine prognostic differences between liver resection (LR) and percutaneous radiofrequency ablation (PRFA) for hepatocellular carcinoma (HCC) based on preoperative predicted microvascular invasion (MVI) risk. METHODS: Data on consecutive patients who underwent LR (n = 1344) or PRFA (n = 853) for hepatitis B virus-related HCC within the Milan criteria (MC) were analyzed. A preoperative nomogram was used to estimate MVI risk. Overall survival (OS), time to recurrence, and patterns of recurrence were compared using propensity score matching. RESULTS: The concordance indices of the nomogram to predict MVI were 0.813 and 0.781 among LR patients with HCC within the MC or ≤ 3 cm, respectively. LR and PRFA resulted in similar 5-year recurrence and OS for patients with nomogram-predicted low-risk of MVI. LR provided better 5-year recurrence and OS versus PRFA for patients with high-risk of MVI (71.6% vs. 80.7%, p = 0.013; 47.9% vs. 34.0%, p = 0.002, for HCC within the MC; 62.3% vs. 78.8%, p = 0.020; 63.6% vs. 38.3%, p = 0.015, for HCC ≤ 3 cm). Among high-risk patients, LR was associated with lower recurrence and improved OS compared with PRFA, on multivariate analysis [hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.63-0.97, and HR 0.68, 95% CI 0.52-0.88, for HCC within the MC; HR 0.51, 95% CI 0.32-0.81, and HR 0.47, 95% CI 0.26-0.84, for HCC ≤ 3 cm], and resulted in less early and local recurrence than PRFA (42.4% vs. 54.8%, p = 0.007, and 31.2% vs. 46.1%, p = 0.007, for HCC within the MC; 27.9% vs. 50.8%, p = 0.016, and 15.6% vs. 39.5%, p = 0.046, for HCC ≤ 3 cm). CONCLUSIONS: LR was oncologically superior over PRFA for early HCC patients with predicted high-risk of MVI. LR was associated with better local disease control than PRFA in these patients.