Radiomics model based on contrast-enhanced computed tomography imaging for early recurrence monitoring after radical resection of AFP-negative hepatocellular carcinoma.

BACKGROUND: Although radical surgical resection is the most effective treatment for hepatocellular carcinoma (HCC), the high rate of postoperative recurrence remains a major challenge, especially in patients with alpha-fetoprotein (AFP)-negative HCC who lack effective biomarkers for postoperative recurrence surveillance. Emerging radiomics can reveal subtle structural changes in tumors by analyzing preoperative contrast-enhanced computer tomography (CECT) imaging data and may provide new ways to predict early recurrence (recurrence within 2 years) in AFP-negative HCC. In this study, we propose to develop a radiomics model based on preoperative CECT to predict the risk of early recurrence after surgery in AFP-negative HCC. PATIENTS AND METHODS: Patients with AFP-negative HCC who underwent radical resection were included in this study. A computerized tool was used to extract radiomic features from the tumor region of interest (ROI), select the best radiographic features associated with patient's postoperative recurrence, and use them to construct the radiomics score (RadScore), which was then combined with clinical and follow-up information to comprehensively evaluate the reliability of the model. RESULTS: A total of 148 patients with AFP-negative HCC were enrolled in this study, and 1,977 radiographic features were extracted from CECT, 2 of which were the features most associated with recurrence in AFP-negative HCC. They had good predictive ability in both the training and validation cohorts, with an area under the ROC curve (AUC) of 0.709 and 0.764, respectively. Tumor number, microvascular invasion (MVI), AGPR and radiomic features were independent risk factors for early postoperative recurrence in patients with AFP-negative HCC. The AUCs of the integrated model in the training and validation cohorts were 0.793 and 0.791, respectively. The integrated model possessed the clinical value of predicting early postoperative recurrence in patients with AFP-negative HCC according to decision curve analysis, which allowed the classification of patients into subgroups of high-risk and low-risk for early recurrence. CONCLUSION: The nomogram constructed by combining clinical and imaging features has favorable performance in predicting the probability of early postoperative recurrence in AFP-negative HCC patients, which can help optimize the therapeutic decision-making and prognostic assessment of AFP-negative HCC patients.

Multiplex-genome-editing based rapid directional improvement of complex traits in rice.

Although thousands of genes have been identified or cloned in rice (Oryza sativa) in the last two decades, the majority of them have only been separately characterized in specific varieties or single-gene modified backgrounds, thus limiting their practical application. We developed an optimized multiplex genome editing (MGE) toolbox that can efficiently assemble and stably express up to twelve sgRNA targets in a single plant expression vector. In this study, we established the MGE-based Rapid Directional Improvement (MRDI) strategy for directional improvement of complex agronomic traits in one small-scale rice transformation. This approach provides a rapid and practical procedure, encompassing sgRNA assembly, transgene-free screening and the creation of promising germplasm, by combining the precision of gene editing with phenotype-based field breeding. The MRDI strategy was used to generate the full diversity of twelve main agronomic genes in rice cultivar FXZ for the directional improvement of its growth duration and plant architecture. After applying the MRDI to FXZ, ideal plants with the desired traits of early heading date reduced plant height, and more effective panicles were generated without compromising yield, blast resistance and grain quality. Furthermore, the results of whole-genome sequencing (WGS), including the analysis of structural variations (SVs) and single nucleotide variations (SNVs) in the MGE plants, confirmed the high specificity and low frequency of unwanted mutations associated with this strategy. The MRDI breeding strategy would be a robust approach for exploring and applying crucial agronomic genes, as well as for generating novel elite germplasm in the future.

An algorithm for discovering vital nodes in regional networks based on stable path analysis.

Vital node discovery is a hotspot in network topology research. The key is using the Internet's routing characteristics to remove noisy paths and accurately describe the network topology. In this manuscript, a vital regional routing nodes discovery algorithm based on routing characteristics is proposed. We analyze the stability of multiple rounds of measurement results to overcome the single vantage point's path deviation. The unstable paths are eliminated from the regional network which is constructed through probing for target area, and the pruned topology is more in line with real routing rules. Finally, we weight the edge based on the actual network's routing characteristics and discover vital nodes in combination with the weighting degree. Unlike existing algorithms, the proposed algorithm reconstructs the network topology based on communication and transforms unweighted network connections into weighted connections. We can evaluate the node importance in a more realistic network structure. Experiments on the Internet measurement data (275 million probing results collected in 107 days) demonstrate that: the proposed algorithm outperforms four existing typical algorithms. Among 15 groups of comparison in 3 cities, our algorithm found more (or the same number) backbone nodes in 10 groups and found more (or the same number) national backbone nodes in 13 groups.

The clinical efficacy of ozone combined with steroid in the treatment of discogenic low back pain: a randomized, double-blinded clinical study.

Objective: This randomized double-blinded clinical study is to investigate the clinical efficacy of per-paravertebral disk ozone injection combined with steroids in the treatment of patients with chronic discogenic low back pain (CDLBP). Methods: Group A (N = 60) received a per-paravertebral injection of a steroid mixture of 10 mL with pure oxygen 20 mL, while group B (N = 60) received a per-paravertebral injection of a steroid mixture of 10 mL combined with ozone 20 mL (30 µg/mL). Injections were administered once a week for 3 weeks, with a follow-up of 6 months. Clinical outcomes were assessed at week 1, month 3, and month 6 with the help of Visual Analog Scale (VAS) scores and Macnab efficacy evaluation. Results: The VAS score of both group A (1.65 vs. 6.87, p = 0.000) and group B (1.25 vs. 6.85, p = 0.000) at week 1 was significantly reduced compared to baseline. The effect was sustained at the 3- and 6-month follow-up periods (p < 0.05). Group B had significantly lower VAS scores at month 3 (1.53 vs. 3.82, p = 0.000) and month 6 (2.80 vs. 5.05, p = 0.000) compared to group A, respectively. Based on Macnab criteria, 95 and 96.7% of patients in groups A and B had good rates "excellent plus good" at week 1, respectively. Good rates were significantly higher in group B at month 3 (91.7 vs. 78.3%, p = 0.041) and month 6 (85.0 vs. 68.3%, p = 0.031) compared to group A, respectively. No serious adverse events were noted in both groups. Conclusion: Per-paravertebral injection of steroid and ozone combination resulted in better relief of CDLBP compared to pure oxygen plus steroid. Clinical Trial Registration: ChiCTR2100044434 https://www.chictr.org.cn/showproj.html?proj=121571.

Radiomics model based on contrast-enhanced computed tomography to predict early recurrence in patients with hepatocellular carcinoma after radical resection.

BACKGROUND: Radical resection remains an effective strategy for patients with hepatocellular carcinoma (HCC). Unfortunately, the postoperative early recurrence (recurrence within 2 years) rate is still high. AIM: To develop a radiomics model based on preoperative contrast-enhanced computed tomography (CECT) to evaluate early recurrence in HCC patients with a single tumour. METHODS: We enrolled a total of 402 HCC patients from two centres who were diagnosed with a single tumour and underwent radical resection. First, the features from the portal venous and arterial phases of CECT were extracted based on the region of interest, and the early recurrence-related radiomics features were selected via the least absolute shrinkage and selection operator proportional hazards model (LASSO Cox) to determine radiomics scores for each patient. Then, the clinicopathologic data were combined to develop a model to predict early recurrence by Cox regression. Finally, we evaluated the prediction performance of this model by multiple methods. RESULTS: A total of 1915 radiomics features were extracted from CECT images, and 31 of them were used to determine the radiomics scores, which showed a significant difference between the early recurrence and nonearly recurrence groups. Univariate and multivariate Cox regression analyses showed that radiomics scores and serum alpha-fetoprotein were independent indicators, and they were used to develop a combined model to predict early recurrence. The area under the receiver operating characteristic curve values for the training and validation cohorts were 0.77 and 0.74, respectively, while the C-indices were 0.712 and 0.674, respectively. The calibration curves and decision curve analysis showed satisfactory accuracy and clinical utilities. Kaplan-Meier curves based on recurrence-free survival and overall survival showed significant differences. CONCLUSION: The preoperative radiomics model was shown to be effective for predicting early recurrence among HCC patients with a single tumour.

Metal Ion-Induced Porous MXene for All-Solid-State Flexible Supercapacitors.

MXenes are normally used for energy storage applications. However, large nanosheets and restacking are detrimental to the ion diffusion and thus limit its rate capability. Here, a strategy to prepare flexible and porous MXene-M supercapacitor electrodes can simultaneously enlarge the interlayer spacing between layers and create holes in the layers. As a result, Ti3C2Tx-Mn presents an excellent lifespan, with still 248 F g-1 after 100 000 cycles at a current density of 100 A g-1. Moreover, Ti3C2Tx-Mn-based symmetric all-solid-state supercapacitor exhibits outstanding volumetric energy up to 52.4 mWh cm-3 and retains 38.4 mWh cm-3 at an ultrahigh volumetric power density of 55.3 W cm-3. We believe this work provides an idea for the later regulation of MXene layer spacing and the design of porous structures, and can be widely used in the next-generation high-energy density and power density practical applications.

The impact of heterotrophic bacteria on recalcitrant dissolved organic carbon formation in a typical karstic river.

Recalcitrant dissolved organic carbon (RDOC) resulting from microbial carbon (MCPs) holds promise as a relatively long-term natural carbon sink in marine environments. However, the RDOC formation mechanism remains uncertain in terrestrial aquatic systems. To determine the microbial impacts on autochthonous dissolved organic carbon (DOC), RDOC formation, and the critical influencing bacteria species, spatial changes in hydrochemistry, carbon isotopes, and microbial diversity were investigated in water samples from the karstic Lijiang River, southwest China. Samples were collected at various locations along the river system in May and July 2017. The biodegradable DOC (BDOC), RDOC, soil sourced DOC (SDOC), submerged aquatic vascular plant sourced DOC (PDOC) and microbial sourced DOC (MDOC) were calculated using the in-situ microbial incubation method, stable carbon isotopes and C/N ratio. RDOC accounted for 67% to 93% of DOC concentrations, measuring 1.3 mg/L and 1.2 mg/L in May and July, respectively. In May, BDOC concentrations increased by 0.05 mg/L from 0.18 mg/L to 0.23 mg/L, but decreased by 0.43 mg/L from 0.66 mg/L to 0.23 mg/L in July. The spatiotemporal variation of BDOC indicated photosynthesis was the main BDOC source and induced high autochthonous DOC formation, especially in May. However, RDOC was the dominant accumulation component in Lijiang River. MDOC increased by 0.86 mg/L from 0 to 0.86 mg/L in May and 0.78 mg/L from 0.10 mg/L to 0.88 mg/L in July, which was the dominant accumulated DOC and RDOC component. The abundance of Sporichthyaceae accounted for 3.4%-22.6% in May and Novosphingobium accounted for 3.5%-34.0% in July. These were the critical bacteria species induced MDOC formation, which were confirmed by their abundances in KEGG pathway modules determined by PICRUAST2. These results demonstrate that heterotrophic bacteria dominate autochthonous DOC and RDOC formation in the karst surface river, which is valuable for understanding organic carbon cycling in karstic aquatic systems.

Downregulation of miR-485-3p promotes proliferation, migration and invasion in prostate cancer through activation of TGF-ß signaling.

BACKGROUND: Prostate cancer (PC) is the second leading cause of cancer-related death among men worldwide. Downregulation of miR-485-3p has been revealed to participate in the tumorigenesis and progression of many types of cancer. However, the clinical and biological role of miR-485-3p in PC remains largely unknown. METHODS: The expression of miR-485-3p was analyzed in the published databases and detected in our clinical samples and cell lines by RT-qPCR assay. CCK8, transwell invasion and migration, and colony formation assays were performed to investigate the biological function of miR-485-3p. Bioinformatical analysis, RIP, western blotting and luciferase reporter assays were carried out to explore the downstream mechanism of miR-485-3p. RESULTS: The level of miR-485-3p was downregulated in PC tissues, particularly in primary PC tissues with metastasis relative to normal prostate tissues. miR-485-3p downregulation was positively correlated with poor disease-free and overall survival in patients with PC. Functionally, miR-485-3p overexpression dramatically suppressed the proliferation, migration and invasion ability of PC cells in vitro. Mechanistically, miR-485-3p overexpression suppressed the activity of TGF-ß signaling by targeting TGFBR2 to play tumor-suppressive roles in PC progression. CONCLUSION: Our study reports the miR-485-3p/TGFBR2/ TGF-ß signaling axis in tumor development of PC, suggesting miR-485-3p may be a potential target to develop therapeutic strategies against PC.

Identification of Benign and Malignant Lung Nodules in CT Images Based on Ensemble Learning Method.

BACKGROUND AND OBJECTIVE: Under the background of urgent need for computer-aided technology to provide physicians with objective decision support, aiming at reducing the false positive rate of nodule CT detection in pulmonary nodules detection and improving the accuracy of lung nodule recognition, this paper puts forward a method based on ensemble learning to distinguish between malignant and benign pulmonary nodules. METHODS: Firstly, trained on a public data set, a multi-layer feature fusion YOLOv3 network is used to detect lung nodules. Secondly, a CNN was trained to differentiate benign from malignant pulmonary nodules. Then, based on the idea of ensemble learning, the confidence probability of the above two models and the label of the training set are taken as data features to build a Logistic regression model. Finally, two test sets (public data set and private data set) were tested, and the confidence probability output by the two models was fused into the established logistic regression model to determine benign and malignant pulmonary nodules. RESULTS: The YOLOv3 network was trained to detect chest CT images of the test set. The number of pulmonary nodules detected in the public and private test sets was 356 and 314, respectively. The accuracy, sensitivity and specificity of the two test sets were 80.97%, 81.63%, 78.75% and 79.69%, 86.59%, 72.16%, respectively. With CNN training pulmonary nodules benign and malignant discriminant model analysis of two kinds of test set, the result of accuracy, sensitivity and specificity were 90.12%, 90.66%, 89.47% and 88.57%, 85.62%, 90.87%, respectively. Fused model based on YOLOv3 network and CNN is tested on two test sets, and the result of accuracy, sensitivity and specificity were 93.82%, 94.85%, 92.59% and 92.31%, 92.68%, 91.89%, respectively. CONCLUSION: The ensemble learning model is more effective than YOLOv3 network and CNN in removing false positives, and the accuracy of the ensemble. Learning model is higher than the other two networks in identifying pulmonary nodules.

A low-cost microfluidic platform coupled with light emitting diode for optogenetic analysis of neuronal response in C. elegans.

Optogenetic method is widely used for dissecting the neuronal function and connectivity in a specific neural circuit, which can help understanding how the animal process information and generate behavior. The nematode C. elegans has a simple but complete nervous system, making it an attractive model to study the dynamics signals of neural circuits. However, in vivo analysis on neural circuits usually rely on the complex and expensive optical equipment to allow optogenetic stimulating the neuron while recording its activities in such a freely moving animal. Hence, in this paper we reported a portable optofluidic platform that works based on optical fiber illumination and functional imaging for worm optogenetic manipulation. A light beam from LED laser pen crossing the 3D-printed optical fiber channel is used to activate the neurons specific-expressed with light sensitive proteins ChR-2. The imaging light path is perpendicular to the stimulation light, which allows activating neuron precisely and measuring cellular signals simultaneously. By using such an easy-to-assemble device, optical stimulation of the specific neurons and detection of dynamic calcium responses of other neurons could be proceeded simultaneously. Thus, the developed microfluidic platform puts forward a simple, rapid and low-cost strategy for further neural circuits studies.

Transcriptional downregulation of miR-127-3p by CTCF promotes prostate cancer bone metastasis by targeting PSMB5.

Prostate cancer (PCa) is one of the most common cancers in males and particularly tends to metastasize to bone. Currently, metastatic bone disease is incurable, and new therapies need to be developed. Our study aims to determine the role of miR-127-3p in PCa metastasis to bone. The results demonstrate that miR-127-3p is markedly reduced in bone metastasis-positive PCa tissues relative to that in bone metastasis-negative PCa tissues. Furthermore, overexpressing miR-127-3p inhibits PCa cell invasion and migration in vitro by targeting the proteasome ß-subunit PSMB5. Moreover, CCCTC-binding factor (CTCF) transcriptionally inhibits miR-127-3p by interacting with the miR-127-3p promoter. Collectively, this study uncovers a novel mechanism of the CTCF/miR-127-3p/PSMB5 axis in promoting PCa bone metastasis, indicating that miR-127-3p could function as a promising therapeutic target against bone metastasis.

Joint and plantar loading in table tennis topspin forehand with different footwork.

Table tennis players often execute one-step, side-step or cross-step to move to an appropriate position for topspin forehand. However, to our knowledge, no studies have investigated the footwork effects on lower-limb kinetics and kinematics, which are related to playing performance and injury prevention. This study examined the ground reaction forces, joint kinetics and in-shoe plantar pressure distribution during topspin forehand with three typical footwork patterns. Fifteen male table tennis players performed cross-court topspin forehands in one-step, side-step and cross-step. Force plate, motion capturing, and instrumented insole systems were used to measure ground reaction force, joint moments and plantar pressure variables. One-way ANONA with repeated measures was performed to determine any significant differences between footwork. Results indicated that participants exhibited significantly higher ground reaction force loadings, knee flexion angle, knee moment, ankle inversion and moment during side-step and cross-step compared with one-step footwork condition (p < .01). Plantar pressure data indicated that the significantly higher peak pressure were observed in the total foot, toe, 1st, 2nd and 5th metatarsal regions during side-step and cross-step (p < .01). Additionally, cross-step had induced higher peak pressure in medial midfoot and heel regions than one-step and higher peak pressure in total and 1st metatarsal regions than side-step (p < .01). These results suggest that foot orthotic designs should consider the stronger emphasis on those high-pressured areas and that the differential joint and plantar loadings in side-step and cross-step may provide useful insights to injury mechanism and training protocol development.

Simvastatin functions as a heat shock protein 90 inhibitor against triple-negative breast cancer.

Acetylation plays an important role in regulating the chaperone activity of heat shock protein 90 (Hsp90) during malignant transformation through the stabilization and conformational maturation of oncogenic proteins. However, the functional acetylation sites, potential anticancer drug targets, are still emerging. We found that acetylation at K292 in Hsp90α is critical for the development and treatment of breast cancer. Acetylation at K292 not only augments the affinity of Hsp90 to ATP, cochaperones, and client proteins but it also promotes cancer cell colony formation, migration, and invasion in vitro as well as tumor growth in vivo. Importantly, K292-acetylated Hsp90 has been validated as an exciting anticancer drug target by interfering with the complex formation between K292-acetylated Hsp90 and cochaperone Cdc37, leading to diminishment of kinase client maturation and proteasome-dependent degradation of kinase substrates. Furthermore, we showed that simvastatin prevented, whereas LBH589 promoted, the progression of Hsp90 chaperone cycling and client maturation, resulting in an increment of cell apoptosis by the combination of simvastatin and LBH589 in a mouse xenograft model. These data suggest that simvastatin is a novel Hsp90 inhibitor to disrupt the formation of the K292-acetylated Hsp90/Cdc37 complex in triple-negative breast cancer cells. The combination of simvastatin with LBH589 could be used as a novel therapeutic strategy for triple-negative breast cancer.