Multi-layered computational gene networks by engineered tristate logics.

So far, biocomputation strictly follows traditional design principles of digital electronics, which could reach their limits when assembling gene circuits of higher complexity. Here, by creating genetic variants of tristate buffers instead of using conventional logic gates as basic signal processing units, we introduce a tristate-based logic synthesis (TriLoS) framework for resource-efficient design of multi-layered gene networks capable of performing complex Boolean calculus within single-cell populations. This sets the stage for simple, modular, and low-interference mapping of various arithmetic logics of interest and an effectively enlarged engineering space within single cells. We not only construct computational gene networks running full adder and full subtractor operations at a cellular level but also describe a treatment paradigm building on programmable cell-based therapeutics, allowing for adjustable and disease-specific drug secretion logics in vivo. This work could foster the evolution of modern biocomputers to progress toward unexplored applications in precision medicine.

An integrated machine learning model enhances delayed graft function prediction in pediatric renal transplantation from deceased donors.

BACKGROUND: Kidney transplantation is the optimal renal replacement therapy for children with end-stage renal disease; however, delayed graft function (DGF), a common post-operative complication, may negatively impact the long-term outcomes of both the graft and the pediatric recipient. However, there is limited research on DGF in pediatric kidney transplant recipients. This study aims to develop a predictive model for the risk of DGF occurrence after pediatric kidney transplantation by integrating donor and recipient characteristics and utilizing machine learning algorithms, ultimately providing guidance for clinical decision-making. METHODS: This single-center retrospective cohort study includes all recipients under 18 years of age who underwent single-donor kidney transplantation at our hospital between 2016 and 2023, along with their corresponding donors. Demographic, clinical, and laboratory examination data were collected from both donors and recipients. Univariate logistic regression models and differential analysis were employed to identify features associated with DGF. Subsequently, a risk score for predicting DGF occurrence (DGF-RS) was constructed based on machine learning combinations. Model performance was evaluated using the receiver operating characteristic curves, decision curve analysis (DCA), and other methods. RESULTS: The study included a total of 140 pediatric kidney transplant recipients, among whom 37 (26.4%) developed DGF. Univariate analysis revealed that high-density lipoprotein cholesterol (HDLC), donor after circulatory death (DCD), warm ischemia time (WIT), cold ischemia time (CIT), gender match, and donor creatinine were significantly associated with DGF (P < 0.05). Based on these six features, the random forest model (mtry = 5, 75%p) exhibited the best predictive performance among 97 machine learning models, with the area under the curve values reaching 0.983, 1, and 0.905 for the entire cohort, training set, and validation set, respectively. This model significantly outperformed single indicators. The DCA curve confirmed the clinical utility of this model. CONCLUSIONS: In this study, we developed a machine learning-based predictive model for DGF following pediatric kidney transplantation, termed DGF-RS, which integrates both donor and recipient characteristics. The model demonstrated excellent predictive accuracy and provides essential guidance for clinical decision-making. These findings contribute to our understanding of the pathogenesis of DGF.

Remnant cholesterol and the risk of aortic valve calcium progression: insights from the MESA study.

BACKGROUND: Remnant cholesterol (RC) is implicated in the risk of cardiovascular disease. However, comprehensive population-based studies elucidating its association with aortic valve calcium (AVC) progression are limited, rendering its precise role in AVC ambiguous. METHODS: From the Multi-Ethnic Study of Atherosclerosis database, we included 5597 individuals (61.8 ± 10.1 years and 47.5% men) without atherosclerotic cardiovascular disease at baseline for analysis. RC was calculated as total cholesterol minus high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), as estimated by the Martin/Hopkins equation. Using the adjusted Cox regression analyses, we examined the relationships between RC levels and AVC progression. Furthermore, we conducted discordance analyses to evaluate the relative AVC risk in RC versus LDL-C discordant/concordant groups. RESULTS: During a median follow-up of 2.4 ± 0.9 years, 568 (10.1%) participants exhibited AVC progression. After adjusting for traditional cardiovascular risk factors, the HRs (95% CIs) for AVC progression comparing the second, third, and fourth quartiles of RC levels with the first quartile were 1.195 (0.925-1.545), 1.322 (1.028-1.701) and 1.546 (1.188-2.012), respectively. Notably, the discordant high RC/low LDL-C group demonstrated a significantly elevated risk of AVC progression compared to the concordant low RC/LDL-C group based on their medians (HR, 1.528 [95% CI 1.201-1.943]). This pattern persisted when clinical LDL-C threshold was set at 100 and 130 mg/dL. The association was consistently observed across various sensitivity analyses. CONCLUSIONS: In atherosclerotic cardiovascular disease-free individuals, elevated RC is identified as a residual risk for AVC progression, independent of traditional cardiovascular risk factors. The causal relationship of RC to AVC and the potential for targeted RC reduction in primary prevention require deeper exploration.

Non-contrast-enhanced magnetic resonance urography for measuring split kidney function in pediatric patients with hydronephrosis: comparison with renal scintigraphy.

BACKGROUND: Split kidney function (SKF) is critical for treatment decision in pediatric patients with hydronephrosis and is commonly measured using renal scintigraphy (RS). Non-contrast-enhanced magnetic resonance urography (NCE-MRU) is increasingly used in clinical practice. This study aimed to investigate the feasibility of using NCE-MRU as an alternative to estimate SKF in pediatric patients with hydronephrosis, compared to RS. METHODS: Seventy-five pediatric patients with hydronephrosis were included in this retrospective study. All patients underwent NCE-MRU and RS within 2 weeks. Kidney parenchyma volume (KPV) and texture analysis parameters were obtained from T2-weighted (T2WI) in NCE-MRU. The calculated split KPV (SKPV) percent and texture analysis parameters percent of left kidney were compared with the RS-determined SKF. RESULTS: SKPV showed a significant positive correlation with SKF (r = 0.88, p < 0.001), while inhomogeneity was negatively correlated with SKF (r = - 0.68, p < 0.001). The uncorrected and corrected prediction models of SKF were established using simple and multiple linear regression. Bland-Altman plots demonstrated good agreement of both predictive models. The residual sum of squares of the corrected prediction model was lower than that of the uncorrected model (0.283 vs. 0.314) but not statistically significant (p = 0.662). Subgroup analysis based on different MR machines showed correlation coefficients of 0.85, 0.95, and 0.94 between SKF and SKPV for three different scanners, respectively (p < 0.05 for all). CONCLUSIONS: NCE-MRU can be used as an alternative method for estimating SKF in pediatric patients with hydronephrosis when comparing with RS. Specifically, SKPV proves to be a simple and universally applicable indicator for predicting SKF.

Goal-directed fluid therapy during post-resection phase in low central venous pressure assisted laparoscopic hepatectomy: a randomized controlled superiority trial.

PURPOSE: The purpose of this prospective single blinded randomized controlled trial was to find out whether goal-directed fluid therapy (GDFT) strategy in post-transection period in low central venous pressure (CVP) assisted laparoscopic hepatectomy (LH) has more benefit than traditional fluid strategy. METHODS: Between April 2020 and Dec 2021, patients who were scheduled for laparoscopic liver resection surgery were eligible to participate in the study. Patients were randomly divided into two groups: control group that received traditional fluid strategy in post-transection period in low CVP assisted laparoscopic hepatectomy and GDFT strategy group that received GDFT strategy in post-transection period. The primary outcome parameter is the incidence of postoperative complications. Secondary outcome parameters include perioperative clinical outcomes, postoperative clinical outcomes, length of hospital stay after surgery, postoperative lactic acid, fluids and vasoactive medications during the operation. RESULTS: A total of 159 patients in the control group and 160 patients in the GDFT were included. Two groups had no significant difference in the incidence of postoperative complications including pneumonia (P = 0.34), acute kidney injury (P = 0.72), hepatic insufficiency (P = 0.25), pleural effusion (P = 0.08) and seroperitoneum (P = 1.00), respectively. The amount of perioperative urine output is fewer in GDFT group than in the control group (P = 0.0354), while other perioperative variables and postoperative variables were comparable between two groups. CONCLUSIONS: The results show the implementation of GDFT strategy is not associated with fewer postoperative complications. GDFT strategy did not result in improved outcomes in low CVP-assisted laparoscopic hepatectomy.

The role of regulatory T cells in the pathogenesis of acute kidney injury.

The incidence of acute kidney injury (AKI) is on the rise and is associated with high mortality; however, there are currently few effective treatments. Moreover, the relationship between Tregs and other components of the immune microenvironment (IME) in the pathogenesis of AKI remains unclear. We downloaded four publicly accessible AKI datasets, GSE61739, GSE67401, GSE19130, GSE81741, GSE19288 and GSE106993 from the gene expression omnibus (GEO) database. Additionally, we gathered two kidney single-cell sequencing (scRNA-seq) samples from the Department of Organ Transplantation at Zhujiang Hospital of Southern Medical University to investigate chronic kidney transplant rejection (CKTR). Moreover, we also collected three samples of normal kidney tissue from GSE131685. By analysing the differences in immune cells between the AKI and Non-AKI groups, we discovered that the Non-AKI group contained a significantly greater number of Tregs than the AKI group. Additionally, the activation of signalling pathways, such as inflammatory molecules secretion, immune response, glycolytic metabolism, NOTCH, FGF, NF-κB and TLR4, was significantly greater in the AKI group than in the Non-AKI group. Additionally, analysis of single-cell sequencing data revealed that Tregs in patients with chronic kidney rejection and in normal kidney tissue have distinct biology, including immune activation, cytokine production, and activation fractions of signalling pathways such as NOTCH and TLR4. In this study, we found significant differences in the IME between AKI and Non-AKI, including differences in Tregs cells and activation levels of biologically significant signalling pathways. Tregs were associated with lower activity of signalling pathways such as inflammatory response, inflammatory molecule secretion, immune activation, glycolysis.

Noninvasive Assessment of the Renal Function, Oxford Classification and Prognostic Risk Stratification of IgAN by Using Intravoxel Incoherent Motion Diffusion-Weighted Imaging and Blood Oxygenation Level-Dependent MRI.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Oxford classification including mesangial hypercellularity (M), endothelial hypercellularity (E), segmental sclerosis (S), interstitial fibrosis/tubular atrophy (T), and crescent (C) were recommended to predict the prognosis of IgAN. PURPOSE: To explore whether multiparametric magnetic resonance imaging (MRI) can be applied to assess the renal function, Oxford classification, and risk of progression to end-stage kidney disease within 5 years of IgAN. STUDY TYPE: Prospective. POPULATION: A total of 46 patients with pathologically confirmed IgAN and 20 healthy volunteers. FIELD STRENGTH/SEQUENCE: A 3-T, blood oxygenation level-dependent (BOLD)-MRI, intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI). ASSESSMENT: Two radiologists measured the cortex and medulla T2*, apparent diffusion coefficient (ADC), true diffusion (Dt), pseudo-diffusion (Dp), perfusion fraction (fp). All participants were divided into three groups: group 1, healthy volunteers; group 2, patients with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 ; group 3, patients with eGFR <60 mL/min/1.73 m2 . Or two groups: group A, 5-year risk scores ≤10% and group B, 5-year risk scores >10%. STATISTICAL TESTS: Intraclass correlation coefficient, one-way analysis of variance, least-significant difference, Student's t-test, Pearson product-moment correlation, Spearman's rank correlation, and receiver operating characteristics (ROC) with the area under the curve (AUC). A P value <0.05 was considered statistically significant. RESULTS: Except for cortical Dp, all other MRI parameters showed significant differences between group 1 and group 2. None of the MRI parameters showed a significant correlation with M, E, or C scores. Cortical T2*, Dt, fp, and medullary Dt and fp showed low-to-moderate significant correlations with S scores. Except for cortical and medullary Dp, all other MRI parameters were significantly correlated with T scores. Cortical Dt showed the largest AUC for differentiating group A from group B (AUC = 0.927) and T0 from T1/T2 (AUC = 0.963). DATA CONCLUSION: Imaging by IVIM-DWI and BOLD-MRI could facilitate noninvasive assessment of the renal function, Oxford classification, and prognostic risk of IgAN patients. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 3.

WHO/ISUP grade and pathological T stage of clear cell renal cell carcinoma: value of ZOOMit diffusion kurtosis imaging and chemical exchange saturation transfer imaging.

OBJECTIVES: To evaluate the value of ZOOMit diffusion kurtosis imaging (DKI) and chemical exchange saturation transfer (CEST) imaging in predicting WHO/ISUP grade and pathological T stage in clear cell renal cell carcinoma (ccRCC). METHODS: Forty-six patients with ccRCC were included in this retrospective study. All participants underwent MRI including ZOOMit DKI and CEST. The non-Gaussian mean kurtosis (MK), mean diffusivity (MD), magnetization transfer ratio asymmetry (MTRasym (3.5 ppm)), and Ssat (3.5 ppm)/S0 were analyzed based on different WHO/ISUP grades and pT stages. Binary logistic regression was used to identify the best combination of the parameters. Pearson's correlation coefficients were calculated between CEST and diffusion-related parameters. RESULTS: The ADC, MD, and Ssat (3.5 ppm)/S0 values were significantly lower for higher WHO/ISUP grade tumors, whereas the MK and MTRasym (3.5 ppm) were higher in higher WHO/ISUP grade and higher pT stage tumors. MTRasym (3.5 ppm) combined with MD (AUC, 0.930; 95% CI, 0.858-1.000) showed the best diagnostic efficacy in evaluating the WHO/ISUP grade. MTRasym (3.5 ppm) and MK were mildly positively correlated (r = 0.324, p = 0.028). Ssat (3.5 ppm)/S0 was moderately positively correlated with ADC (r = 0.580, p < 0.001), mildly positively correlated with MD (r = 0.412, p = 0.005), and moderately negatively correlated with MK (r = -0.575, p < .001). CONCLUSION: The microstructural and biochemical assessment of ZOOMit DKI and CEST allowed for the characterization of different WHO/ISUP grades and pT stages in ccRCC. MTRasym (3.5 ppm) combined with MD showed the best diagnostic performance for WHO/ISUP grading. KEY POINTS: • Both diffusion kurtosis imaging (DKI) and chemical exchange saturation transfer (CEST) can be used to predict the WHO/ISUP grade and pathological T stage. • MTRasym (3.5 ppm) combined with MD showed the highest AUC (0.930; 95% CI, 0.858-1.000) in WHO/ISUP grading. • MTRasym at 3.5 ppm showed a positive correlation with mean kurtosis.

Deep Reinforcement Learning-Based One-to-Multiple Cooperative Computing in Large-Scale Event-Driven Wireless Sensor Networks.

Emergency event monitoring is a hot topic in wireless sensor networks (WSNs). Benefiting from the progress of Micro-Electro-Mechanical System (MEMS) technology, it is possible to process emergency events locally by using the computing capacities of redundant nodes in large-scale WSNs. However, it is challenging to design a resource scheduling and computation offloading strategy for a large number of nodes in an event-driven dynamic environment. In this paper, focusing on cooperative computing with a large number of nodes, we propose a set of solutions, including dynamic clustering, inter-cluster task assignment and intra-cluster one-to-multiple cooperative computing. Firstly, an equal-size K-means clustering algorithm is proposed, which activates the nodes around event location and then divides active nodes into several clusters. Then, through inter-cluster task assignment, every computation task of events is alternately assigned to the cluster heads. Next, in order to make each cluster efficiently complete the computation tasks within the deadline, a Deep Deterministic Policy Gradient (DDPG)-based intra-cluster one-to-multiple cooperative computing algorithm is proposed to obtain a computation offloading strategy. Simulation studies show that the performance of the proposed algorithm is close to that of the exhaustive algorithm and better than other classical algorithms and the Deep Q Network (DQN) algorithm.

Safety and Feasibility of Minimally Invasive (Laparoscopic/Robotic-Assisted) Nipple-Sparing Mastectomy Combined with Prosthesis Breast Reconstruction in Breast Cancer: A Single-Center Retrospective Study.

BACKGROUND: Minimally invasive (robotic or laparoscopic-assisted) nipple-sparing mastectomy combined with prosthesis breast reconstruction (NSM-PBR) is associated with smaller scars and greater patient satisfaction. However, the oncological safety of minimally invasive NSM-PBR remains controversial. PATIENTS AND METHODS: This was a retrospective study of patients with breast cancer who underwent breast reconstruction between 1 January 2006 and 20 February 2021. Demographic and clinicopathological characteristics, operation information, postoperative complications, and survival outcomes were analyzed. RESULTS: In all, 292 patients underwent minimally invasive NSM-PBR and 205 underwent open NSM-PBR for breast cancer. In the minimally invasive NSM-PBR group, 268 (91.8%) patients underwent laparoscopy and 24 (8.2%) patients underwent robot-assisted NSM-PBR. Mean operation time in the minimally invasive NSM-PBR group was significantly longer than that in the open NSM-PBR group (P = 0.023). Mean intraoperative blood loss was significantly less in the minimally invasive NSM-PBR group (P < 0.05). There was no significant between-group difference in total complications. Similarly, there were no significant between-group differences in overall survival, recurrence-free survival, and local recurrence rate (P = 0.450, P = 0.613, and P = 0.679, respectively). CONCLUSIONS: The complication, recurrence, and mortality rates in minimally invasive NSM-PBR group were comparable to those in open NSM-PBR group. Our preliminary results are encouraging and suggest that minimally invasive NSM-PBR affords good cosmetic results and its oncological safety is comparable to that of open surgery.

All-in-one approaches for triple-negative breast cancer therapy: metal-phenolic nanoplatform for MR imaging-guided combinational therapy.

BACKGROUND: Conventional chemotherapy has poor efficacy in triple-negative breast cancer (TNBC) which is highly heterogeneous and aggressive. Imaging-guided therapy is usually combined with diverse treatment modalities, could realize the integration of diagnosis and treatments. Therefore, the primary challenge for combinational therapy is designing proper delivery systems to accomplish multiple synergistic effects. RESULTS: Herein, a facile nanoplatform was manufactured to fulfill the all-in-one approaches for TNBC combinational therapy. Fe3+-based metal-phenolic networks (MPNs) with bovine serum albumin (BSA) modification served as drug delivery carriers to encapsulate bleomycin (BLM), forming BFE@BSA NPs. The self-assembly mechanism, pH-responsive drug release behavior, and other physicochemical properties of this system were characterized. The potential of BFE@BSA NPs as photothermal transduction agents and magnetic resonance imaging (MRI) contrast agents was explored. The synergistic anti-tumor effects consisting of BLM-induced chemotherapy, Fenton reactions-mediated chemodynamic therapy, and photothermal therapy-induced apoptosis were studied both in vitro and in vivo. Once internalized into tumor cells, released BLM could cause DNA damage, while Fenton reactions were initiated to produce highly toxic •OH. Upon laser irradiation, BFE@BSA NPs could convert light into heat to achieve synergistic effects. After intravenous administration, BFE@BSA NPs exhibited great therapeutic effects in 4T1 tumor xenograft model. Moreover, as T1-weighted MRI contrast agents, BFE@BSA NPs could provide diagnosis and treatment monitoring for individualized precise therapy. CONCLUSIONS: A nano-system that integrated imaging and combinational therapy (chemotherapy, chemodynamic therapy and photothermal therapy) were developed to kill the tumor and monitor therapeutic efficacy. This strategy provided an all-in-one theranostic nanoplatform for MRI-guided combinational therapy against TNBC.

A New Hypersonic Wind Tunnel Force Measurement System to Reduce Additional Bending Moment and Avoid Time-Varying Stiffness.

In order to improve traditional hypersonic wind tunnel airframe/propulsion integrated aerodynamic testing technology for hypersonic vehicles, a new force measurement system called the aerodynamic force measuring support (AFMS) was designed. The AFMS effectively overcomes the defect that the traditional internal box-balance occupies a large amount of internal space in the aircraft test model, which makes the airframe/propulsion integrated aerodynamic test more difficult. The AFMS also alleviates the interference of the additional bending moment caused by the non-coincidence between the calibration center of traditional external box-balance and the gravity center of the aircraft test model, innovatively designing a convex structure in the joint part of the force measuring system. Furthermore, the AFMS effectively overcomes the time-varying stiffness of joints caused by test model vibration in hypersonic wind tunnel testing, which eventually leads to test errors. Compared with the traditional box-balance, the AFMS proposed in this study has sufficient design space. This ensures more thorough aerodynamic decomposition of the AFMS and less interference between channels, whilst also having the advantages of the large support stiffness of traditional box-balance. Thus, the AFMS provides a new technical path for airframe/propulsion integrated aerodynamic testing of air-breathing hypersonic vehicles in a hypersonic wind tunnel.

Palladium-Catalyzed Oxidative Coupling of the Allenic C-H Bond with α-Diazo Esters: Synthesis of [3]Dendralenes.

A palladium-catalyzed highly regio- and stereoselective allenic C-H oxidative coupling with α-diazo esters is developed. The reaction pathway involves allylic palladium carbene as the key intermediate, which is followed by a carbene migratory insertion process. The reaction proceeds efficiently under mild conditions without external base, providing substituted [3]dendralenes bearing various functional groups.

A magnetic resonance nanoprobe with STING activation character collaborates with platinum-based drug for enhanced tumor immunochemotherapy.

BACKGROUND: Immunochemotherapy is a potent anti-tumor strategy, however, how to select therapeutic drugs to enhance the combined therapeutic effect still needs to be explored. METHODS AND RESULTS: Herein, a magnetic resonance nanoprobe (MnP@Lip) with STING (Stimulator of INterferon Genes) activation character was synthesized and co-administered with platinum-based chemotherapeutics for enhanced immunochemotherapy. MnP@Lip nanoparticles was prepared by simple fabrication process with good reproducibility, pH-sensitive drug release behavior and biocompatibility. In vitro experiments elucidated that Mn2+ can promote the polarization of M0 and/or M2 macrophages to M1 phenotype, and promote the maturation of BMDC cells. Upon Mn2+ treatment, the STING pathway was activated in tumor cells, mouse lung epithelial cells, and immune cells. More importantly, anti-tumor experiments in vivo proved that MnP@Lip combined with platinum-based chemotherapeutics increased T cells infiltration in the tumor microenvironment, and inhibited tumor growth in the orthotopic therapeutic and postoperative tumor models. CONCLUSIONS: This kind of therapeutic strategy that combined MnP@Lip nanoparticles with platinum-based chemotherapeutics may provide a novel insight for immunochemotherapy.

ß-Glucan Extracted from Highland Barley Alleviates Dextran Sulfate Sodium-Induced Ulcerative Colitis in C57BL/6J Mice.

Inflammatory bowel disease (IBD), which significantly affects human health, has two primary presentations: Crohn's disease and ulcerative colitis (UC). Highland barley is the most common food crop for Tibetans and contains much more ß-glucan than any other crop. Highland barley ß-glucan (HBBG) can relieve the gastrointestinal dysfunction and promote intestines health. This study aimed to evaluate whether HBBG can relieve UC in mice. A mouse model of UC was established by adding 2% dextran sulfate sodium (DSS) to drinking water for 1 week. UC was alleviated after the introduction of the HBBG diet, as indicated by reductions in the disease activity index (DAI) score, histopathological damage, and the concentration of colonic myeloperoxidase (MPO), along with an improvement in colonic atrophy. Furthermore, we found that HBBG can increase the relative transcriptional levels of genes encoding ZO-1, claudin-1, occludin, and mucin2 (MUC2), thereby reducing intestinal permeability. Additionally, HBBG maintained the balance of proinflammatory and anti-inflammatory cytokines and modulated the structure of the intestinal flora.

Myofibroblast-Derived Exosomes Contribute to Development of a Susceptible Substrate for Atrial Fibrillation.

OBJECTIVE: Atrial fibrosis plays a critical role in atrial fibrillation (AF). A key event in the pathogenesis of fibrosis is the activation of fibroblasts (FBs) into myofibroblasts (MFBs). Paracrine factors released from MFBs lead to ion channel expression changes in cardiomyocytes (CMs). Downregulation of L-type calcium channel Cav1.2 expression is a hallmark of AF-associated ionic remodeling. However, whether exosome (Exo)-mediated crosstalk between MFBs and CMs regulates Cav1.2 expression remains unknown. METHODS: Atrial FBs and CMs were isolated and cultured from neonatal rats by enzymatic digestion. The activation of FBs into MFBs was induced by angiotensin II. Co-culture assay and in vitro Exo treatment were used to determine the effect of MFB-derived Exos on Cav1.2 expression. Confocal Ca2+ imaging was performed to examine the adrenergic stimulation-elicited Ca2+ influx signals. The levels of potential Cav1.2-inhibitory microRNAs (miRNAs) were measured by qRT-PCR. RESULTS: Untreated FBs expressed limited amounts of alpha smooth muscle actin (α-SMA), while angiotensin II induced a significant upregulation of α-SMA-expressing MFBs. Co-cultures of MFBs and CMs resulted in downregulation of Cav1.2 expression in CMs, which was largely abolished by pretreatment of MFBs with exosomal inhibitor GW4869. More importantly, treatment with MFB-derived Exos caused repression of Cav1.2 expression in CMs. Additionally, the adrenergic receptor agonist-elicited Ca2+ influx signals in CMs were remarkably attenuated by pretreatment with MFB-derived Exos, corresponding to the paralleled change in Cav1.2 expression. Finally, miR-21-3p, a potential Cav1.2-inhibitory miRNA, was enriched in MFB-derived Exos and upregulated in CMs in response to MFB-derived Exos. CONCLUSION: We uncover an Exo-mediated crosstalk between MFBs and CMs, contributing to increased vulnerability to AF by reducing the expression of Cav1.2 in CMs.

Cumulative Sum Analysis of the Operator Learning Curve for Robot-Assisted Mayo Clinic Level I-IV Inferior Vena Cava Thrombectomy Associated with Renal Carcinoma: A Study of 120 Cases at a Single Center.

BACKGROUND This study aimed to use cumulative sum analysis of the operator learning curve for robot-assisted Mayo Clinic level I-IV inferior vena cava (IVC) thrombectomy associated with renal carcinoma, and describes the development of an optimized operative procedure at a single center. MATERIAL AND METHODS A retrospective study included 120 patients with Mayo Clinic level I-IV IVC thrombus who underwent robotic surgery between 2013 and 2018. Points in the learning curve were identified using cumulative sum analysis, and their impact was assessed by multiple regression analysis. Perioperative indicators analyzed included operative time, estimated blood loss, early complications, and the 90-day progression rate. RESULTS Cumulative sum analysis identified three phases in the learning curve of robot-assisted IVC thrombectomy. The median operative time decreased from 265 min (range, 212-401 min) to 207 min (range, 146-276 min) (p=0.003), the median estimated blood loss decreased from 775 ml (range, 413-1500 ml) to 300 ml (range, 163-813 ml) (p=0.006), and the early complication rate decreased from 52.5% to 15.0% (p<0.001). Multivariate analysis showed that for an initial 40 cases and a further 80 cases, the learning phase, the affected side, the Mayo Clinic level, and the surgical method were independent factors that affected operative time, estimated blood loss, and the rate of early complications. CONCLUSIONS Experience from an initial 40 cases and a further 80 cases of Mayo Clinic level I-IV IVC thrombectomy associated with renal carcinoma were found to provide acceptable surgical and clinical outcomes.

Automatic Recognition of Sucker-Rod Pumping System Working Conditions Using Dynamometer Cards with Transfer Learning and SVM.

Sucker-rod pumping systems are the most widely applied artificial lift equipment in the oil and gas industry. Accurate and intelligent working condition recognition of pumping systems imposes major impacts on oilfield production benefits and efficiency. The shape of dynamometer card reflects the working conditions of sucker-rod pumping systems, and different conditions can be indicated by their typical card characteristics. In traditional identification methods, however, features are manually extracted based on specialist experience and domain knowledge. In this paper, an automatic fault diagnosis method is proposed to recognize the working conditions of sucker-rod pumping systems with massive dynamometer card data collected by sensors. Firstly, AlexNet-based transfer learning is adopted to automatically extract representative features from various dynamometer cards. Secondly, with the extracted features, error-correcting output codes model-based SVM is designed to identify the working conditions and improve the fault diagnosis accuracy and efficiency. The proposed AlexNet-SVM algorithm is validated against a real dataset from an oilfield. The results reveal that the proposed method reduces the need for human labor and improves the recognition accuracy.

Single Image De-Raining via Improved Generative Adversarial Nets.

Capturing images under rainy days degrades image visual quality and affects analysis tasks, such as object detection and classification. Therefore, image de-raining has attracted a lot of attention in recent years. In this paper, an improved generative adversarial network for single image de-raining is proposed. According to the principles of divide-and-conquer, we divide an image de-raining task into rain locating, rain removing, and detail refining sub-tasks. A multi-stream DenseNet, termed as Rain Estimation Network, is proposed to estimate the rain location map. A Generative Adversarial Network is proposed to remove the rain streaks. A Refinement Network is proposed to refine the details. These three models accomplish rain locating, rain removing, and detail refining sub-tasks, respectively. Experiments on two synthetic datasets and real world images demonstrate that the proposed method outperforms state-of-the-art de-raining studies in both objective and subjective measurements.

Oncofetal HLF transactivates c-Jun to promote hepatocellular carcinoma development and sorafenib resistance.

BACKGROUND AND AIMS: The unique expression pattern makes oncofetal proteins ideal diagnostic biomarkers and therapeutic targets in cancer. However, few oncofetal proteins have been identified and entered clinical practice. METHODS: Fetal liver, adult liver and hepatocellular carcinoma (HCC) tissues were employed to assess the expression of hepatic leukaemia factor (HLF). The impact of HLF on HCC onset and progression was investigated both in vivo and in vitro. The association between HLF and patient prognosis was determined in patient cohorts. The correlation between HLF expression and sorafenib benefits in HCC was further evaluated in patient cohorts and patient-derived xenografts (PDXs). RESULTS: HLF is a novel oncofetal protein which is reactivated in HCC by SOX2 and OCT4. Functional studies revealed that HLF transactivates c-Jun to promote tumour initiating cell (TIC) generation and enhances TIC-like properties of hepatoma cells, thus driving HCC initiation and progression. Consistently, our clinical investigations elucidated the association between HLF and patient prognosis and unravelled the close correlation between HLF levels and c-Jun expression in patient HCCs. Importantly, HLF/c-Jun axis determines the responses of hepatoma cells to sorafenib treatment, and interference of HLF abrogated c-Jun activation and enhanced sorafenib response. Analysis of patient cohorts and PDXs further suggests that HLF/c-Jun axis might serve as a biomarker for sorafenib benefits in HCC patients. CONCLUSIONS: Our findings uncovered HLF as a novel oncofetal protein and revealed the crucial role of the HLF/c-Jun axis in HCC development and sorafenib response, rendering HLF as an optimal target for the prevention and intervention of HCC.