Search

The quality of covert communications is determined by the choice of communication channels and the design of data embedding schemes. Recently, the Bitcoin system is prevalent as a covert communication channel. The consensus mechanism requires participants to spread their found valid blocks under an adjustable difficulty, which provides a stable periodic broadcast channel. Moreover, senders and receivers are difficult to be traced, because the Bitcoin system is pseudonymous. However, since the historical data in the ledger cannot be removed from the Bitcoin system, the openness and the persistent storage of the ledger in the Bitcoin system post new challenges when designing data embedding schemes. More concreteness, most traditional data embedding schemes either design by heuristic or empirical algorithms or use a fixed field to embed data in the transactions. Therefore, the covert data can be recognized once the algorithm is leaked or the pattern is explored. In this article, we first propose a Hash Chain-based Covert Data Embedding (HC-CDE) Scheme. The embedded transactions are difficult to be discovered. We further propose an Elliptic Curve Diffie-Hellman Chain-based Covert Data Embedding (ECDHC-CDE) Scheme to enhance the security of the HC-CDE scheme. Experimental analysis on the Bitcoin Testnet verifies the security and the efficiency of the proposed schemes.

Mobilized peripheral blood has become the primary source of hematopoietic stem cells for both autologous and allogeneic stem cell transplantation. Granulocyte colony-stimulating factor (G-CSF) is currently the standard agent used in the allogeneic setting. Despite the high mobilization efficacy in most donors, G-CSF requires 4–5 days of daily administration, and a small percentage of the donors fail to mobilize an optimal number of stem cells necessary for a safe allogeneic stem cell transplant. In this study, we retrospectively reviewed 1361 related allogeneic donors who underwent stem cell mobilization at Washington University. We compared the standard mobilization agent G-CSF with five alternative mobilization regimens, including GM-CSF, G-CSF+GM-CSF, GM-CSF + Plerixafor, Plerixafor and BL-8040. Cytokine-based mobilization strategies (G-CSF or in combination with GM-CSF) induce higher CD34 cell yield after 4–5 consecutive days of treatment, while CXCR4 antagonists (plerixafor and BL-8040) induce significantly less but rapid mobilization on the same day. Next, using a large dataset containing the demographic and baseline laboratory data from G-CSF–mobilized donors, we established machine learning (ML)–based scoring models that can be used to predict patients who may have less than optimal stem cell yields after a single leukapheresis session. To our knowledge, this is the first prediction model at the early donor screening stage, which may help identify allogeneic stem cell donors who may benefit from alternative approaches to enhance stem cell yields, thus ensuring safe and effective stem cell transplantation.

OBJECTIVE Delta-24-RGD is an oncolytic adenovirus that is capable of replicating in and killing human glioma cells. Although intratumoral delivery of Delta-24-RGD can be effective, systemic delivery would improve its clinical application. Bone marrow–derived human mesenchymal stem cells (BM-hMSCs) obtained from healthy donors have been investigated as virus carriers. However, it is unclear whether BM-hMSCs can be derived from glioma patients previously treated with marrow-toxic chemotherapy or whether such BM-hMSCs can deliver oncolytic viruses effectively. Herein, the authors undertook a prospective clinical trial to determine the feasibility of obtaining BM-hMSCs from patients with recurrent malignant glioma who were previously exposed to marrow-toxic chemotherapy. METHODS The authors enrolled 5 consecutive patients who had been treated with radiation therapy and chemotherapy. BM aspirates were obtained from the iliac crest and were cultured to obtain BM-hMSCs. RESULTS The patient-derived BM-hMSCs (PD-BM-hMSCs) had a morphology similar to that of healthy donor–derived BM-hMSCs (HD-BM-hMSCs). Flow cytometry revealed that all 5 cell lines expressed canonical MSC surface markers. Importantly, these cultures could be made to differentiate into osteocytes, adipocytes, and chondrocytes. In all cases, the PD-BM-hMSCs homed to intracranial glioma xenografts in mice after intracarotid delivery as effectively as HD-BM-hMSCs. The PD-BM-hMSCs loaded with Delta-24-RGD (PD-BM-MSC-D24) effectively eradicated human gliomas in vitro. In in vivo studies, intravascular administration of PD-BM-MSC-D24 increased the survival of mice harboring U87MG gliomas. CONCLUSIONS The authors conclude that BM-hMSCs can be acquired from patients previously treated with marrow-toxic chemotherapy and that these PD-BM-hMSCs are effective carriers for oncolytic viruses.

Background Atherosclerosis is a chronic inflammatory disease in which macrophage polarization plays an important role in contribution to atherosclerotic plaque formation and stability. Here we tested the effect of miR-92 regulation on the development of atherosclerosis beyond tumorigenesis and explored the potential mechanism. Methods and results In the present study, bone marrow derived macrophages (BMDMs), mouse peritoneal macrophages (MPMs), and human macrophages were used to test the expression of miR-92. Here we noticed miR-92 levels were enhanced in classic M1 macrophage but decreased in alternative M2 macrophage, respectively. In vitro, we demonstrated that macrophages transfected with miR-92 inhibitor attenuated proinflammatory cytokine secretion represented by polarized M1 markers but promoted anti-inflammatory state that was indicative of an M2 phenotype. Mechanistically, miR-92 was found to directly interact with KLF4 and we further identified a requirement role of KLF4 in mediating the effect of miR-92 silencing macrophage polarization. Concomitantly, miR-92 inhibition treated ApoE-/- mice promoted macrophage polarization toward alternative M2 macrophage, thus protecting against atherosclerotic plaque formation and preventing a vulnerable phenotype. Conclusion miR-92 inhibition promoted alternative macrophage activation and attenuated atherosclerosis regression partially regulated in a KLF4-dependent manner, which indicated that miR-92/KLF4 axis may serve as a promising strategy for prevention of atherosclerotic diseases.

Natural killer (NK) cells are a promising alternative to T cells for cancer immunotherapy. Adoptive therapies with allogeneic, cytokine-activated NK cells are being investigated in clinical trials. However, the optimal cytokine support after adoptive transfer to promote NK cell expansion, and persistence remains unclear. Correlative studies from 2 independent clinical trial cohorts treated with major histocompatibility complex-haploidentical NK cell therapy for relapsed/refractory acute myeloid leukemia revealed that cytokine support by systemic interleukin-15 (IL-15; N-803) resulted in reduced clinical activity, compared with IL-2. We hypothesized that the mechanism responsible was IL-15/N-803 promoting recipient CD8 T-cell activation that in turn accelerated donor NK cell rejection. This idea was supported by increased proliferating CD8+ T-cell numbers in patients treated with IL-15/N-803, compared with IL-2. Moreover, mixed lymphocyte reactions showed that IL-15/N-803 enhanced responder CD8 T-cell activation and proliferation, compared with IL-2 alone. Additionally, IL-15/N-803 accelerated the ability of responding T cells to kill stimulator-derived memory-like NK cells, demonstrating that additional IL-15 can hasten donor NK cell elimination. Thus, systemic IL-15 used to support allogeneic cell therapy may paradoxically limit their therapeutic window of opportunity and clinical activity. This study indicates that stimulating patient CD8 T-cell allo-rejection responses may critically limit allogeneic cellular therapy supported with IL-15. This trial was registered at www.clinicaltrials.gov as #NCT03050216 and #NCT01898793.

Recent works on salient object detection (SOD) mainly focus on pixel-level classification by leveraging fully convolutional network (FCN)-based encoder-decoder models. In this paper, considering that the context relation plays a critical role in defining a salient object appearing in a scene, we propose a local-to-global context-aware feature augmentation network, namely LGCNet. A two-branch attention-based context relation modeling structure is designed by considering global context-aware information based on foreground/background cues and global feature representations. A pixel-wise self-attention mechanism is then incorporated for both branches to propagate global context information to local feature representations. As a result, a coarse-to-fine salient object detection model is formulated. The whole framework can be trained in an end-to-end manner under a deeply supervised framework. Experimental results demonstrate the effectiveness of key components proposed in our LGCNet. Our LGCNet achieves promising results in comparison with 18 state-of-the-art methods on six widely-used benchmark datasets.

Objective To evaluate the proprioceptive and clinical function of the knee joint after anterior cruciate ligament reconstruction (ACLR) with various amounts of remnant preserved with as few confounding factors as possible. Methods This retrospective study included 46 patients who underwent ACLR with remnant preservation between March 2013 and February 2019. These patients had less than 6 months injury‐to‐surgery interval and no concomitant injuries. The researchers divided these subjects into two groups based on the length of the remnant preserved after ACLR, with group A defined as having more than 1/3 of the original length preserved and group B defined as less than 1/3 of the original length preserved. Clinical scores were obtained using the Lysholm knee scoring scale and the Tegner activity scale. The Lysholm score was calculated preoperatively, at 3, 6, and 12 months postoperatively, and at the last follow up. The Tegner score was calculated preoperatively, at 12 months postoperatively and at the last follow up. Anterior laxity was measured using the KT2000 arthrometer preoperatively and at 12 months postoperatively. Proprioceptive function was evaluated through reproduction of passive positioning (RPP) and threshold to detection of passive motion (TDPM). Both RPP and TDPM were measured at the angle of 15° at 3, 6, and 12 months postoperatively. Unpaired t‐tests were performed to investigate the difference in each parameters between the two groups. Results In the present study, 20 patients were classified into group A and 26 into group B. All patients were followed up for an average of 34.70 ± 12.79 months. All 46 patients were satisfied with the outcome of the surgery and no complications were reported at the end of the study. No significant differences were found between the two groups in terms of the Lysholm score and anterior laxity by KT2000 at all time points. The Tegner score was significantly higher in group A at 12 months postoperatively and at the final follow‐up. In addition, group A's RPP was significantly better than that of group B's when tested at the angles of 15° and 30° at 3 months postoperatively, and at the angle of 15° at 6 months postoperatively. Group A's TDPM was also significantly better than that of group B's at all three tested angles at 3 months postoperatively, and at the angle of 15° at 6 months postoperatively. Conclusion Patients with ACLR with more than 1/3 of the original length preserved demonstrated a higher activity level 12 months postoperatively and better proprioceptive function at 15° of extension at 3 and 6 months postoperatively.

Detecting circularly polarized light (CPL) signals is the key technique in many advanced sensing technologies. Over recent decades, many efforts have been devoted to both the material design and the device engineering of CPL photodetectors. CPL detectors with different sensing wavelengths have distinct applications in bio-imaging, drug discovery, and information encryption. In this review, we first introduce the working principle of state-of-the-art CPL photodetectors followed by a general material design strategy. We then systematically summarize the recent progress on the chiral materials developed for CPL detection, including inorganic metamaterials, organics, hybridized materials, etc. We compare and analyse the photocurrent dissymmetry factors of these systems and provide perspectives on strategies to improve the dissymmetry factors and extend the detection wavelength. We believe that the information we include in this review would attract broader interest from researchers working on different aspects of organic and hybridized semiconductor materials and devices.

Enteroviruses (EVs) are common causes of viral encephalitis in children. To better understand the epidemiological and pathological characteristics of EV encephalitis, we enrolled suspected encephalitis patients younger than 15 years old in Hangzhou, China, from October, 2016 to September, 2019 for cerebrospinal fluid (CSF) collection and analyses. A total of 7735 CSF samples were collected, among which 330 (4.27%) were positive for the EV genome. The positivity rate was significantly higher in boys than girls (χ2 = 5.68, P = 0.02). The monthly case numbers peaked from June to August (80.30%). Among the different age groups, the 0-2 months age group showed the highest number of cases (28.48% of all cases). The 6-7 years (10.82%) and 9-10 years (9.29%) age groups showed the highest EV-positivity rates among suspected encephalitis cases. Sixty-two EV-positive and 53 control CSF samples were collected for Bio-Plex Pro human cytokine assays that simultaneously tested 48 cytokines. Principle component analyses showed significant separation between EV-positive and control samples, but insignificant separation between children and newborns. The levels of 28 cytokines and chemokines were significantly elevated in EV-positive group including many pro-inflammatory and a few anti-inflammatory cytokines, as well as chemokines belonging to the CC and CXC subfamilies. Only one cytokine, SCGF-β, showed a decrease in the EV-positive group. Thus, this study revealed age, sex and seasonal preferences for EV encephalitis incidences in children and identified many cytokines dysregulated during EV encephalitis. This article is protected by copyright. All rights reserved.

Highlights • Exercise induces a profound alteration in epigenetics, which mediates the beneficial effects of exercise. • Exercise not only modifies epigenetics in the heart to promote cardiac health, but also modifies epigenetics in other tissues, which reduces risks of cardiac disease or affords cardioprotection through exerkines. • Exercise-modulated circulating non-coding RNAs are secreted from multiple tissues and shuttled by exosomes, acting as a new kind of exerkine that plays an important role in cardioprotection., With the rising incidence of cardiovascular diseases, the concomitant mortality and morbidity impose huge burdens on quality of life and societal costs. It is generally accepted that physical inactivity is one of the major risk factors for cardiac disease and that exercise benefits the heart in both physiological and pathologic conditions. However, the molecular mechanisms governing the cardioprotective effects exerted by exercise remain incompletely understood. Most recently, an increasing number of studies indicate the involvement of epigenetic modifications in the promotion of cardiac health and prevention of cardiac disease. Exercise and other lifestyle factors extensively induce epigenetic modifications, including DNA/RNA methylation, histone post-translational modifications, and non-coding RNAs in multiple tissues, which may contribute to their positive effects in human health and diseases. In addition, several studies have shown that maternal or paternal exercise prevents age-associated or high-fat diet-induced metabolic dysfunction in the offspring, reinforcing the importance of epigenetics in mediating the beneficial effects of exercise. It has been shown that exercise can directly modify cardiac epigenetics to promote cardiac health and protect the heart against various pathological processes, or it can modify epigenetics in other tissues, which reduces the risk of cardiac disease and affords cardioprotection through exerkines. An in-depth understanding of the epigenetic landscape of cardioprotective response to exercise will provide new therapeutic targets for cardiac diseases. This review, therefore, aimed to acquaint the cardiac community with the rapidly advancing and evolving field of exercise and epigenetics., Graphical abstract Image, graphical abstract

Summary Mimicking the natural photosynthetic process, the artificial photosynthesis for CO2 conversion based on chemical photocatalyst has depicted an excellent blueprint for achieving artificial carbon cycle. However, the current artificial chemical photocatalysts do not have the upper hand in biological systems regarding the activity and selectivity for conversion of CO2 to multi-carbon products. In this regard, natural photosynthesis could offer numerous sources of bioinspiration for artificial chemical photocatalysts to solve their bottlenecks. In this perspective, we highlight the recent successes in this emerging field to show the development of bioinspired photosynthetic systems from semi-artificial photosynthetic biohybrids to biomimetic photocatalytic systems. Meanwhile, the common fundamentals behind various designed biohybrids and biomimetic systems are elucidated. Toward future development, we discuss the challenges and opportunities in the research field.

Background and Purpose: Prognostic factors for outcome of endovascular treatment remains to be investigated in patients with acute basilar artery occlusion. We aimed to assess the prognostic value of a novel pretreatment diffusion-weighted imaging score: The Pons-Midbrain and Thalamus (PMT) score. Methods: Eligible patients who underwent endovascular treatment due to acute basilar artery occlusion were reviewed. The PMT score was a diffusion-weighted imaging–based semiquantitative scale in which the infarctions of pons, midbrain, and thalamus were fully considered. The PMT score was assessed as well as the posterior circulation Acute Stroke Prognosis Early Computed Tomography Score and Brain Stem Score. Good outcomes were defined as a modified Rankin Scale score of ≤3 at 90-day and successful reperfusion as Thrombolysis in Cerebral Infarction grades 2b/3. The associations between baseline clinical parameters and good outcomes were evaluated with logistic regression. Results: A total of 107 patients with pretreatment magnetic resonance imaging were included in this cohort. The baseline PMT score (median [interquartile range], 3 [1–5] versus 7 [5–9]; P P =0.001) were significantly lower in good outcome group; the posterior circulation Acute Stroke Prognosis Early Computed Tomography Score was higher in good outcome group without statistical significance. As a result of receiver operating characteristic curve analyses, the posterior circulation Acute Stroke Prognosis Early Computed Tomography Score showed poor prognostic accuracy for good outcome (area under the curve, 0.60 [95% CI, 0.49–0.71]; P =0.081); The baseline PMT score showed significantly better prognostic accuracy for 90-day good outcome than the Brain Stem Score and National Institutes of Health Stroke Scale (area under the curve, 0.80 versus 0.68 versus 0.78, P =0.003). In addition, favorable PMT score P P P Conclusions: In patients with acute basilar artery occlusion following endovascular treatment, the pretreatment diffusion-weighted imaging based PMT score showed good prognostic value for clinical outcome.

Battery energy-storage system (BESS) based on the modular multilevel converter (MMC) can flexibly manage the battery packs integrated into submodules, where the battery pack can directly or through a small capacitor connect to the rear-end half-bridge circuit for reducing cost and volume caused by an additional dc–dc converter. But the alternating current ripples will cause substantial additional charge throughput for battery packs and, consequently, reduce the battery lifetime in theory. Therefore, this article proposes a variable dc-link voltage regulation method for a single-phase MMC-BESS. In specific, the phase disposition (PD) modulation scheme is improved to properly bypass the gating signals with unnecessary conduction during operation and the modified gating signals will be rearranged for balancing the states-of-charge and states-of-health. Doing so, the additional charge throughput could be significantly reduced compared with the traditional phase-shift modulation and PD modulation. Even comparing with the ideal dc current charging/discharging, the proposed method will only increase slight additional charge throughput and nearly negligible capacity loss. The experimental results of a 6.6 kW/6.6 kWh single-phase MMC-BESS prototype verified the performance of the proposed method.

Vascular mitochondria constantly integrate signals from environment and respond accordingly to match vascular function to metabolic requirements of the organ tissues, while mitochondrial dysfunction contributes to vascular aging and pathologies such as atherosclerosis, stenosis, and hypertension. As an effective lifestyle intervention, exercise induces extensive mitochondrial adaptations through vascular mechanical stress and the increased production and release of reactive oxygen species and nitric oxide that activate multiple intracellular signaling pathways, among which peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) plays a critical role. PGC-1α coordinates mitochondrial quality control mechanisms to maintain a healthy mitochondrial pool and promote endothelial nitric oxide synthase activity in vasculature. The mitochondrial adaptations to exercise improve bioenergetics, balance redox status, protect endothelial cells against detrimental insults, increase vascular plasticity, and ameliorate aging-related vascular dysfunction, thus benefiting vascular health. This review highlights recent findings of mitochondria as a central hub integrating exercise-afforded vascular benefits and its underlying mechanisms. A better understanding of the mitochondrial adaptations to exercise will not only shed light on the mechanisms of exercise-induced cardiovascular protection, but may also provide new clues to mitochondria-oriented precise exercise prescriptions for cardiovascular health.

Endovascular treatment's (EVT) safety and efficacy have been proven in treating acute ischemic stroke (AIS) due to large vessel occlusion (LVO). However, limited data exist in different stroke subtypes. We aimed to investigate the differences in efficacy and safety of EVT for acute LVO according to different stroke subtypes.A total of 1635 AIS patients with LVO undergoing EVT from a prospective cohort of the Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke (ANGEL-ACT) registry were classified into three types according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria. We compared the primary outcome: 90-day modified Rankin Scale (mRS) score, the secondary outcomes: 90-day mRS (0-1, 0-2, and 0-3), successful recanalization (mTICI 2b/3), and complete recanalization (mTICI 3), and the safety outcomes: death within 90 days, parenchymal hemorrhage (PH), and symptomatic intracranial hemorrhage (SICH) among the three subtypes of stroke patients. Then, multivariable logistic regression models adjusting for potential baseline-confounding variables to determine the associations between stroke subtypes and safety and efficacy endpoints were performed. Finally, we performed subgroup analyses to explore discrepancies in the relationships.EVT of cardioembolic LVO (CE-LVO) had a higher rate of mTICI 3 (71.7% vs. 65.9% and 63.2%; P = 0.024) and a higher rate of PH (13.8% vs. 5.4% and 6.7%; P 0.001) when compared to other stroke subtypes. Even multivariable analysis demonstrated that CE-LVO was associated with mTICI 3 [adjusted odds ratio (OR), 1.50 (95% CI 1.04-2.17)] and PH [adjusted OR, 1.97 (95% CI 1.09-3.55)]. However, the 90-day mRS distribution and 90-day mRS (0-1, 0-2, and 0-3) did not differ among the stroke subtypes, and nor did the SICH (P 0.05).Functional outcomes were similar among different stroke subtypes. Despite a higher rate of complete recanalization, there is an increased risk of parenchymal hemorrhage in CE-LVO.Clinical trial registration number: NCT03370939.

Three-dimensional magnetic resonance elastography (3D-MRE) allows for multiparametric modeling of both elastic and viscous tissue characteristics. Our aim was to compare 3D-MRE with conventional liver shear stiffness assessment in gauging obstructive jaundice (OJ), predicting the adequacy of biliary decompression after drainage, and discriminating OJ from liver fibrosis. Patients with no histories of liver disease (n = 201) were studied in retrospect, grouped by bilirubin levels as no jaundice (NJ ≤ 2 mg/dL; n = 75), mild OJ (>2 mg/dL and ≤ 4 mg/dL; n = 56), and severe OJ (> 4 mg/dL; n = 70). For comparison, another 75 patients with chronic hepatitis B and C infections and histologically proven liver fibrosis were similarly analyzed. Each patient underwent spin-echo echo-planar-imaging MRE at 60 Hz with 3D wave postprocessing. Logistic regression and ordinary regression models were used to compare the 3D-MRE model with liver shear stiffness. Liver shear stiffness, loss modulus, and damping ratio were incorporated into a 3D-MRE model, which significantly outperformed shear stiffness in predicting OJ severity (accuracy: 0.801 vs 0.672; p

BACKGROUND Severe bony Bankart lesions are a difficult challenge in clinical treatment and research. The current treatment methods consist mostly of Latarjet-Bristow surgery and its modified procedures. While good results have been achieved, there are also complications such as coracoid fracture, bone graft displacement, and vascular and nerve injury. AIM To analyze the techniques and biomechanical properties of transversely fixing a bone block from the scapular spine using bone allograft pins with suture threads to repair bony Bankart lesions. METHODS Fresh human shoulder joint specimens and a cadaver specimen model for scapular bone grafting with allograft pin fixation for repair of bony Bankart lesions were used. When the humeral rotation angles were 0°, 30°, 60° and 90°, and the axial loads were 30 N, 40 N, and 50 N, the humerus displacement was studied by biomechanical experiments. RESULTS When the angle of external rotation of the humerus was 0°, 30°, 60°, and 90°, with axial loads of 30 N, 40 N, and 50 N, the data of the normal control group, allograft pin repair group, and titanium alloy hollow screw repair group were compared with each other by the q-test, which showed that there were no statistically differences among the three groups (P > 0.05). CONCLUSION The joints repaired with bone block from the scapular spine transversely fixed with allograft bony pins to repair bony Bankart lesions show good mechanical stability. The bone block has similar properties to normal glenohumeral joints in terms of biomechanical stability.

Many patients with ocular myasthenia gravis (OMG) progress to generalized disease within the first 2 years of the onset of ocular symptoms. Several retrospective studies have identified risk factors associated with generalization, however these studies included patients on immunosuppression therapy or those undergoing thymectomy, which may reduce the generalization risk. In this study we explored the risk factors for generalization in non-immunosuppressed and non-thymectomized patients with OMG. Data from patients with OMG treated at seven tertiary hospitals in China were retrospectively reviewed. Clinical characteristics, including sex, age at onset, symptoms at onset, comorbid autoimmune diseases, neostigmine test response, repetitive nerve stimulation (RNS) findings, presence of serum anti-acetylcholine receptor antibody (AChR-Ab), and thymic status based on radiological and pathological studies, were collected. The main outcome measure was disease generalization. The follow-up period was defined as the date of ocular symptom onset to the date of confirmation of generalization or immunotherapy initiation, or last follow-up (defined as 60 months). The Cox proportional hazards model was used to assess the risk factors for generalization. Overall, 572 patients (269 women) were eligible for inclusion in the analysis, of whom 144 developed generalization. The mean (standard deviation) onset age was 45.5 (19.8) years, and the median (interquartile range) follow-up period was 14.5 (7.0–47.3) months. Multivariable Cox regression analysis demonstrated that both early-onset (adjusted hazard ratio [aHR] 5.34; 95% confidence interval [CI] 1.64–17.36; p = 0.005) and late-onset (aHR 7.18; 95% CI 2.22–23.27; p = 0.001) in adulthood, abnormal RNS findings (aHR 3.01; 95% CI 1.97–4.61; p

Photometric stereo aims to reconstruct 3D geometry by recovering the dense surface orientation of a 3D object from multiple images under differing illumination. Traditional methods normally adopt simplified reflectance models to make the surface orientation computable. However, the real reflectances of surfaces greatly limit applicability of such methods to real-world objects. While deep neural networks have been employed to handle non-Lambertian surfaces, these methods are subject to blurring and errors, especially in high-frequency regions (such as crinkles and edges), caused by spectral bias: neural networks favor low-frequency representations so exhibit a bias towards smooth functions. In this paper, therefore, we propose a self-learning conditional network with multi-scale features for photometric stereo, avoiding blurred reconstruction in such regions. Our explorations include: (i) a multi-scale feature fusion architecture, which keeps high-resolution representations and deep feature extraction, simultaneously, and (ii) an improved gradient-motivated conditionally parameterized convolution (GM-CondConv) in our photometric stereo network, with different combinations of convolution kernels for varying surfaces. Extensive experiments on public benchmark datasets show that our calibrated photometric stereo method outperforms the state-of-the-art.

Aims The purpose of our study was to evaluate the feasibility and efficacy of cardiac resynchronization therapy (CRT) via left bundle branch pacing (LBBP-CRT) compared with optimized biventricular pacing (BVP) with adaptive algorithm (BVP-aCRT) in heart failure with reduced left ventricular ejection fraction ≤35% (HFrEF) and left bundle branch block (LBBB). Methods and results One hundred patients with HFrEF and LBBB undergoing CRT were prospectively enrolled in a non-randomized fashion and divided into two groups (LBBP-CRT, n = 49; BVP-aCRT, n = 51) in four centres. Implant characteristics and echocardiographic parameters were accessed at baseline and during 6-month and 1-year follow-up. The success rate for LBBP-CRT and BVP-aCRT was 98.00% and 91.07%. Fused LBBP had the greatest reduced QRS duration compared to BVP-aCRT (126.54 ± 11.67 vs. 102.61 ± 9.66 ms, P Conclusions The feasibility and efficacy of LBBP-CRT demonstrated better electromechanical resynchronization and higher clinical and echocardiographic response, especially higher super-response than BVP-aCRT in HFrEF with LBBB.

Objective. To investigate the clinical application of microsurgery using the cerebellar medulla fissure approach in severe ventricular hemorrhage with casting of the fourth ventricle and its effect on neurological recovery. Methods. A total of 80 patients with severe intraventricular hemorrhage accompanied by casting and dilation of the fourth ventricle who were admitted to the neurosurgery department between July 2019 and December 2020 were randomly divided into an observation group and a control group, with 40 patients in each group. The drainage tube extubation time and length of hospital stay of the two groups were compared. The 3-day hematoma clearance of the two groups was observed. Postoperative consciousness was evaluated by GCS, and the patients’ recovery was evaluated by GOS at three months. The activities of daily living (ADL) scores of the two groups were compared to evaluate patients’ postoperative self-care ability. The incidence of postoperative complications in the two groups was collected. Independent risk factors for poor prognosis were analyzed by logistics regression. Results. The postoperative hospitalization time and the drainage tube extubation time in the observation group were significantly lower than those in the control group. The ratio of hematoma clearance ≥90% in the observation group was significantly higher than that of the control group. Postoperative GCS scores and GOS scores in the observation group were significantly higher than those of the control group. The rate of postoperative complications in the observation group was significantly lower than that of the control group. The rate of good ADL grading in the observation group was significantly higher than that in the control group. Age and surgical method were independent risk factors for poor prognosis. Conclusion. Microsurgery using the cerebellar medulla fissure approach can effectively improve the condition of severe ventricular hemorrhage with casting of the fourth ventricle and promote the recovery of patients’ neurological function.

Purpose For ball screw feed system, a sudden start or stop has a great influence on the transmission stiffness, so the axial stiffness mutation of feed system will occur. The purpose of this paper is to study the influence of acceleration on the transmission stiffness and dynamic characteristics of the ball screw feed system. Design/methodology/approach Taking the ball screw feed system as a research object, on the basis of the Hertz contact theory and the mixed element method, axial stiffness model and dynamic model are established. And the system stability was analyzed by the time history diagram and Phase-plane portrait diagram. The feed system was analyzed theoretically and experimentally, the experimental results are in good agreement with the model results. Findings Lead screw lead angle, preload, load and start acceleration affected ball-screw pair, bearing and transmission stiffness. And the load, nut contact stiffness, bearing contact stiffness, preload have a large effect on the transmission stiffness. The results show that a certain acceleration value will make the axial stiffness abrupt change. Originality/value This research provides a useful theoretical support for ensuring a good dynamic for the ball screw feed system.

Rapid and sensitive point-of-care testing (POCT) is an extremely critical mission in practical applications, especially for rigorous military medicine, home health care, and in the third world. Here, we report a visual POCT method for adenosine triphosphate (ATP) detection based on Taylor rising in the corner of quadratic geometries between two rod surfaces. We discuss the principle of Taylor rising, demonstrating that it is significantly influenced by contact angle, surface tension, and density of the sample, which are controlled by ATP-dependent rolling circle amplification (RCA). In the presence of ATP, RCA reaction effectively suppresses Taylor-rising behavior, due to the increased contact angle, density, and decreased surface tension. Without addition of ATP, untriggered RCA reaction is favorable for Taylor rising, resulting in a significant height. With this proposed method, visual sensitive detection of ATP without the aid of other instruments is realized with only a 5 μL droplet, which has good selectivity and a low detection limit (17 nM). Importantly, this visual method provides a promising POCT tool for user-friendly molecular diagnostics.

BackgroudThe goal of this study was to determine if the choice of imaging paradigm performed in the emergency department influences the procedural or clinical outcomes after mechanical thrombectomy (MT).MethodsThis is a retrospective comparative outcome study which was conducted from the ANGEL-ACT registry. Comparisons were made between baseline characteristics and clinical outcomes of patients with acute ischemic stroke undergoing MT with non-contrast head computed tomography (NCHCT) alone versus patients undergoing NCHCT plus non-invasive vessel imaging (NVI) (including CT angiography (with or without CT perfusion) and magnetic resonance angiography). The primary outcome was the modified Rankin Scale (mRS) score at 90 days. Secondary outcomes included change in mRS score from baseline to 90 days, the proportions of mRS 0–1, 0–2, and 0–3, and dramatic clinical improvement at 24 hours. The safety outcomes were any intracranial hemorrhage (ICH), symptomatic ICH, and mortality within 90 days.ResultsA total of 894 patients met the inclusion criteria; 476 (53%) underwent NCHCT alone and 418 (47%) underwent NCHCT + NVI. In the NCHCT alone group, the door-to-reperfusion time was shorter by 47 min compared with the NCHCT + NVI group (219 vs 266 min, PConclusionsIn patients selected for MT using NCHCT alone versus NCHCT + NVI, there were improved procedural outcomes and smaller increases in baseline mRS scores at 90 days.

OBJECTIVE: The goal of this study was to develop rat models of partial body irradiation with bone-marrow sparing (leg-out PBI), to test medical countermeasures (MCM) of both acute radiation syndrome (ARS) and delayed effects of acute radiation exposure (DEARE) under the FDA animal rule. METHODS: The leg-out PBI models were developed in female and male WAG/RijCmcr rats at doses of 12.5–14.5 Gy. Rats received supportive care consisting of fluids and antibiotics. Gastrointestinal ARS (GI-ARS) was assessed by lethality to day 7 and diarrhea scoring to day 10. Differential blood counts were analyzed between days 1–42 for the natural history of hematopoietic ARS (H-ARS). Lethality and breathing intervals (BI) were measured between days 28–110 to assess delayed injury to the lung (L-DEARE). Kidney injury (K-DEARE) was evaluated by measuring elevation of blood urea nitrogen (BUN) between days 90–180. RESULTS: The LD(50/30), including both lethality from GI-ARS and H-ARS, for female and male rats is 14.0 Gy and 13.5 Gy respectively, while the LD(50/7) for only GI-ARS is 14.3 Gy and 13.6 Gy respectively. The all-cause mortality, including ARS and L-DEARE, through 120 days (LD(50/120)) is 13.5 Gy and 12.9 Gy respectively. Secondary end points confirmed occurrence of 4 distinct sequelae representing GI, hematopoietic, lung and kidney toxicities after leg-out PBI. CONCLUSION: Adult rat models of leg-out PBI developed showed the acute and long-term sequelae of radiation damage that has been reported in human radiation exposure case studies. Sex-specific differences were observed in the DRR between females and males. These rat models are among the most useful for the development and approval of countermeasures for mitigation of radiation injuries under the FDA animal rule.

A tunable bandwidth add-drop filter in ideal quasi-critical coupling (QCC) state was analyzed in theory in detail and demonstrated in experiment, with two vector modes HE $^{\rm X}_{11}$ and HE $^{\rm Y}_{11}$ coupled single whispering gallery mode (WGM) as its basic configuration. In the experiment, the bandwidth tuning range at the Drop port was from 54.0 MHz to 775.8 MHz with the conversion efficiency maintained above 95%, and bandwidth tuning range at the Through port was from 6.6 MHz to 720.6 MHz with the insertion loss fluctuation less than 5%. The demonstrated filter gains advantages of stable efficiency, narrow band, and broad bandwidth tuning range, which will be helpful for its application in microwave photonics, narrow linewidth lasers and nonlinear optics.

This paper presents a trilevel risk-averse strategy to configure the grid-scale energy storage systems (ESS) in active distribution network. Unlike the traditional planning framework, which presumes that ESS and renewable energy sources (RES) are cooperatively planned, we consider a practical situation that the siting choice of individual RES owners could be conflict with systems operation target of hosting capacity improvement. To address this challenge, a trilevel ESS planning formulation with “min-max” risk constraint is developed. Also, a scenario-based stochastic program model is incorporated in the lower level problem to handle the random fluctuation of RES outputs. As the resulting risk-constrained trilevel formulation is computationally difficult, we develop a customized column-and-constraint generation algorithm with finite convergence. Numerical studies on 33-bus test system and a real-world 56-bus distribution network indicate that the proposed methodology can effectively enhance the robustness of look-ahead ESS configuration against those non-cooperative and uncertain integration choices for renewable energy construction. Moreover, our customized algorithm demonstrates a superior solution capacity and scalability to support the efficient decisions for risk-averse storage planning.

Optimal charging scheduling of electric vehicles with renewable energy could greatly save the electricity cost in parking lots, and also helps for environment protection. However, uncertainties of renewable energy and electric vehicles charging demand bring great challenges to obtaining the optimal charging policy. To this end, in this paper, a state aggregation based dynamic programming method is presented for such a stochastic charging scheduling problem. Specifically, first, a new Markov decision process based formulation is established for the multi‐stage stochastic programming problem. Second, a novel state‐aggregation method is proposed to relieve the dimension curse due to large state‐action space without sacrificing the optimality of the charging policy. Besides, the consistency of the problem before and after state aggregation also could be verified by proposed theorems both on feasibility and optimality. Moreover, economic efficiency and computational efficiency are both improved in numerical testing, which shows the effectiveness of the proposed method.

Small-signal models (SSM) of modular multilevel converter (MMC) based HVDC grid under unbalanced grid conditions in recent literatures do not consider interactions between MMC and dc network. Therefore, it is necessary to correctly model the double-fundamental-frequency zero-sequence circulating currents (DFF-ZSCC) existing under unbalanced grid conditions, although they can be suppressed to avoid penetrating into dc side. In view of that, a general and modular small-signal modeling method of MMC-HVDC grid under unbalanced grid condition is developed. Firstly, a general d-q transformation process for multi-sequence and multi-frequency components is introduced to build the state-space model of MMC electric part in d-q frame. Secondly, the SSM of dc network, which is divided into dc- and double-fundamental-frequency parts, is developed based on the existing frequency-dependent-cascaded-pi (FDC-PI) cable model. Then, to interface MMC stations with dc network under unbalanced grid conditions, a general method to synchronize the variables of double fundamental frequency at dc side of each MMC station is introduced to compose the SSM of the entire HVDC grid from SSMs of each MMC and dc network. Finally, taking a three-terminal MMC-HVDC grid as an example, two SSMs of the MMC-HVDC grid with FDC-PI cable model and single-PI cable model are developed in Matlab, respectively. The small-signal dynamics and stability of both SSMs of the grid under unbalanced grid conditions are compared to validate the accuracy and stability of the proposed SSM of the whole HVDC grid. The simulation results validate the correctness and effectiveness of the proposed modular modeling method.

Background Cancer-associated fibroblasts (CAFs) in the tumour microenvironment are associated with poor prognosis and chemoresistance in multiple solid tumours. However, there is a lack of universal measures of CAFs in colorectal cancer (CRC). The aim of this study was to assess the utility of a fibroblast-related gene signature (FRGS) for predicting patient outcomes and reveal its relevant mechanism. Methods The GSE39582 dataset, which includes 316 CRC patients who did not receive adjuvant chemotherapy was used as a discovery cohort to identify the prognostic fibroblast-related genes (FRGs). A total of 1352 CRC patients were divided into one training cohort (GSE39582, n = 461) and two validation cohorts (TCGA, n = 338; meta-validation, n = 553) for the construction of the FRGS and the verification of its prognostic value in stage II/III CRC patients. Functional annotation and analysis were performed to explore the underlying mechanism. The ability of the FRGS to predict immunotherapy response was further tested in a clear cell renal cell carcinoma (ccRCC) cohort. Results An 11-gene signature that had prognostic value for stage II/III CRC patients in both validation cohorts was developed (TCGA cohort: HR = 1.90, 95% CI 1.16–3.12, P P P P P > 0.05). Similar results were found in the TCGA cohort. Integrated with clinical characteristics, the FRGS was confirmed to be an independent prognostic factor in the multivariate analysis after adjustment for tumour TNM stage (GSE39582 cohort: HR = 3.19, 95% CI 1.88–5.41, P P = 0.007; meta-validation cohort: HR = 2.99, 95% CI 1.44–6.21, P = 0.003). Furthermore, the enrichment analysis found that the antitumour immune response was suppressed and the infiltration of CD4 T cells and M1 macrophages was depressed in the high CAF group. The FRGS was also found to have value in predicting for immunotherapy response in the ccRCC cohort. Conclusions The 11-gene FRGS had independent prognostic value for CRC patients, as well as utility in the prediction of benefit from chemotherapy. CAFs in the tumour microenvironment might have an impact on the prognosis of CRC patients via inhibiting immune response.

Gas is associated with coal mining; it commonly exists in the coal seam. It is one of the major dangers during the production because its reaction between the coal masses may induce the gas-coal outburst as well as it being an expositive matter. The gas accident has caused a huge amount of property damage and casualties. Therefore, the primary precaution for coal mining is gas control. At present, drilling and extraction are the main approaches for gas accident prevention. After drilling, the ground pressure will be released; the gas which is in a free state or absorbed in the coal seam will be easy to extract as the migration channel is enhanced. Hence, one of the most concerned problems is the stress redistribution of the coal and rock mass around the borehole. In practical engineering, there are many joints distributed in the coal and rock strata, so it is necessary to investigate the effect of the drilling in the jointed coal and rock mass. In this paper, the boundary element model of the borehole in the jointed coal and rock mass is established to study the influence of joints on the stress and displacement field. The following results can be obtained. The number of joints has a significant effect on the maximum displacement of the coal and rock mass. The maximum displacement increases with the number of the joint. The position of the maximum displacement shifts from the boundary of the borehole to the far field. Meanwhile, it can be found that the displacement may reach a peak value when the joint angle is 30° and if the joint number is less than 4, and the maximum displacement may occur under the joint angle of 45° and if the joints number continuous increases. The von Mises stress has a trend of increasing with the number of joints when the joint angle is less than 30°, while it has a decreasing trend when the joint angle is larger than 30°. The max stress may occur at the joint angle of 15°. The maximum shear stress occurs mostly in the No. 4 joint and the No.7 joint. When the joint angle is 30°, the maximum shear stress occurs in the No. 3 joint and the No. 4 joint. The overlap of the position of the maximum von Mises stress or the maximum displacement with different joint angles or different numbers of joint leads to a reexploration of such positions. The position of the maximum von Mises stress and the maximum displacement o is relatively steady, which locates symmetrically around the borehole. The line between the points that behaves as the maximum von stress is approximately perpendicular to the joint direction.

BackgroundEarly neurological deterioration (END) may occur in some patients with acute large vessel occlusion (LVO) undergoing endovascular treatment (EVT). Despite several clear causes of END, such as symptomatic intracranial hemorrhage, failure of recanalization, and intraprocedure complications, a particular END, termed unexplained END (ENDunexplained), exists. We aimed to investigate the incidence, independent predictors, and clinical impact of ENDunexplained after EVT in patients with acute LVO.MethodsSubjects were selected from the ANGEL-ACT registry. ENDunexplained was defined as ≥4-point increase in the National Institutes of Health Stroke Scale (NIHSS) score between baseline and 24 hours after EVT, without the causes listed above. Logistic regression analyses were performed to determine the independent predictors of ENDunexplained, as well as the association between ENDunexplained and 90-day outcomes assessed by modified Rankin Scale (mRS) score.ResultsAmong the 1557 enrolled patients, the incidence of ENDunexplained was 4.3% (67/1557). Admission NIHSS ≤8 (OR=6.88, 95% CI 3.86 to 12.26, p5 (OR=2.82, 95% CI 1.61 to 4.94, p3 (OR=2.11, 95% CI 1.14 to 3.89, p=0.018) were associated independently with a high risk of ENDunexplained. Furthermore, patients with ENDunexplained were associated with a shift toward worse 90-day outcomes (mRS 5 vs 3, common OR=5.24, 95% CI 3.22 to 8.52, pConclusionsENDunexplained associated with poor 90day outcomes occurred in 4.3% of patients with acute LVO undergoing EVT. Several independent predictors of ENDunexplained were identified in this study, which should be considered in daily practice to improve acute LVO management.Clinical trial Registrationhttp://wwwclinicaltrialsgovNCT03370939.

Dimensional optimization is important for planetary rovers to reach good performance, such as high mobility, stability, and low energy consumption. The paper presents a dimensional optimization for a planetary rover with rocker-bogie suspension. During the optimization process, the influence of dimensions on the actuation requirements is studied based on kinetostatics and terramechanics. The objective function is built considering the average driving torque requirements in the most common type of windblown terrain in Mars called megaripples. The optimal dimension design is reached through the genetic algorithm, and the influences of dimensional parameters on rover performances are studied by drawing performance atlases. This work realizes the consideration of energy consumption in the design phase of a planetary rover. Finally, the results guide the design of a rover prototype and are validated by a series of experiments.

Celiac disease (CD) is a chronic immune-mediated intestinal disease with genetic susceptibility. It is characterized by inflammatory damage to the small intestine after ingestion of cereals and products containing gluten protein. In recent years, the global prevalence rate of CD has been approximately 1%, and is gradually increasing. CD patients adhere to a gluten-free diet (GFD) throughout their entire life. However, it is difficult to adhere strictly to a GFD. Untreated CD may be accompanied by gastrointestinal symptoms, such as diarrhea, abdominal pain, and extraintestinal symptoms caused by secondary malnutrition. Many studies have suggested that CD is associated with intestinal tumors such as enteropathy-associated T-cell lymphoma (EATL), small bowel cancer (SBC), and colorectal cancer. In this study, we reviewed related studies published in the literature to provide a reference for the prevention and treatment of intestinal tumors in patients with CD. Compared with the general population, CD patients had a high total risk of SBC and EATL, but not colorectal cancer. The protective effect of GFD on CD-related malignancies is controversial. Further studies are needed to confirm whether GFD treatment can reduce the risk of intestinal neoplasms in CD.

Aim Aurora kinase A (AURKA) is a pleiotropic serine/threonine kinase that orchestrates mitotic progression. Paclitaxel stabilises microtubules and disrupts mitotic spindle assembly. The combination of AURKA inhibitor (alisertib) plus paclitaxel may be synergistic in rapidly proliferative cancers. We evaluated the safety and maximum tolerated dose (MTD) of alisertib in combination with nab-paclitaxel and its preliminary efficacy in patients with refractory high-grade neuroendocrine tumours (NETs). Method This is a two-part, Phase 1 study. In Part A (dose escalation), a standard 3 + 3 design was used to determine MTD. In Part B (dose expansion), patients with predominantly refractory high-grade NETs were enrolled. Results In total, 31 patients were enrolled and treated (16 in Part A and 15 in Part B). The MTD of alisertib was 40 mg BID on D1-3 per week and nab-paclitaxel 100mg/m2 weekly: 3 weeks, 1 week off. Dose-limiting toxicity was neutropenia, and other common side-effects included fatigue, mucositis, and diarrhoea. In Part A, a patient with small-cell lung cancer with partial response (PR) was treated for more than 2 years, whereas four other patients with pancreatic ductal adenocarcinoma (one patient), small cell lung cancer (SCLC) (two patients), or high-grade NET (one patient) achieved stable disease (SD). In Part B, 13 of 15 enrolled patients had high-grade NETs. Of these, one had PR, and four had SD for more than 10 months. Conclusions The combination of alisertib and nab-paclitaxel has manageable side-effect profile and showed promising preliminary efficacy in high-grade NETs, warranting further testing. Trial registration ClinicalTrials.gov identifier: NCT01677559 .

This communication presents a planar phased array designed with an enhanced reflection bandwidth, a wide-angle scan, and a broadband low backscattering. On one hand, an improved substrate integrated waveguide (SIW) cavity-backed slot antenna which supports dual resonant modes is designed and utilized as the array element. The dual-resonance element presents the advantages of wideband reflection, wide-beam radiation, and compact size, which has the benefit for the wideband wide-angle scan of the proposed phased array. On the other hand, a coding metasurface, which consists of four specially arranged unit cells, is presented and surrounds the slot array. Based on the specially designed coding metasurface, the array gain is enhanced and a broadband scattering reduction is realized. Both simulated and experimental results indicate that the designed phased array supports a main-beam scan up to 60° and a 3 dB beam coverage up to 75° in an active reflection band of 10.1–11.6 GHz. Besides, the results also show that the radar cross section (RCS) has the reduction from 6.2 to 16.3 GHz and from 6.2 to 15.2 GHz for TM and TE polarizations, respectively.

The luminescence modulation behaviour under the in-situ electric field of rare-earth doped KSr2Nb5O15 ceramics opened a new door for the development of dielectric materials. Where the understanding the effect of rare-earth doping on the electric properties of host, especially at the similar doping concentration with luminescence researches (low concentrations) is very important for the exploration of mechanism of electric-luminescent coupling effect. In this work, Nd3+-doped KSr2Nb5O15 (KSN-xNd) ceramics were synthesized, and the electric properties were investigated systematically. Our results suggest that the Nd3+ doping slightly increased the phase transition temperatures and improved the piezoelectric response of KSr2Nb5O15. Most importantly, a bidirectional dielectric tunability is revealed in KSr2Nb5O15. The dielectric permittivity can be adjusted by the DC electric bias, with tunability ranging from −12.3% to 21.9%. The related mechanism and relationship between the bidirectional dielectric tunability and ferroelectricity are revealed by temperature-dependent dielectric and ferroelectric characterization. The researches of electric properties and bidirectional dielectric tunability of KSN-based ceramics paved the way to further exploration of electric-luminescent coupling mechanism.

Aim: Cancer-associated fibroblasts (CAFs) are closely related to epithelial-mesenchymal transition (EMT) and chemoresistance in various cancers. Patients & methods: Experiments in vivo and retrospective studies were applied to explore the role of CAFs in epithelial ovarian cancer (EOC). Results: We found that CXCL12 expression was significantly increased in interstitial CAFs by immunofluorescence. CAF-derived CXCL12 induced EMT though CXCR4/Wnt/β-catenin pathway in EOC cells. Inhibited EMT led to increased apoptosis and cisplatin sensitivity. Multivariate regression analysis shows that CXCL12 expression in the stromal cells and cytoreduction satisfaction are independent prognostic markers of platinum-containing chemotherapy sensitivity in 296 EOC patients. Conclusion: CAFs may activate the Wnt/β-catenin pathway in EOC cells via CXCL12/CXCR4 axis, and then induce EMT and cisplatin resistance.

Because of the excellent static and fatigue performance, the interference-fit bolted structure has a wide application prospect in the joint field. In this paper, an improved spring-mass stiffness analytical prediction model is established for the interference-fit bolted single-lap laminated composite structure. The influences of interference-fit percentage, bolt preload, secondary bending and interface frictions are considered in the model. Combined with experimental research, the value of secondary bending moment coefficient ε is studied, and the correctness of the analytical model is verified. Based on the improved stiffness model, parametric research and regression analysis on the interference-fit percentage, preload, friction, laminate width and material properties are carried out and show that the overall structure stiffness is obviously affected by ε value, laminate width and laminates properties. The stiffness decreases with the increase of ε and increases with the increase of laminate width. And as the key factors, the interference-fit percentage mainly affects the joint local friction and bolt shear stiffness, the preload and friction coefficient mainly affect the local friction, and the laminates sizes and properties directly affect the overall structural stiffness.

Diabetic nephropathy (DN) is a common complication of diabetes. The Notch pathway plays an important role in podocyte injury and decreases the expression of podocyte-specific proteins in DN. However, the exact mechanisms are still elusive. The purpose of this study was to investigate the effect of the Notch pathway on podocyte injury by regulating Kruppel-like factor 4 (KLF4) in high glucose (HG)-induced podocytes. The expression of the Notch pathway and KLF4 was regulated in HG-induced podocytes. Western blotting was used to detect the protein expression of Notch1, Notch intracellular domain 1 (NICD1), KLF4, nephrin, and integrin β1. The mRNA levels of Notch1, KLF4, nephrin, and integrin β1 were determined by real-time polymerase chain reaction. HG increased the expression of Notch1 and NICD1 in podocytes and inhibited the expression of KLF4 (p

Background: Neuroimaging has played a primary role in predicting intracerebral hemorrhage (ICH) recurrence of cerebral amyloid angiopathy (CAA); however, the utilities of biomarkers in CAA-related ICH and cognitive impairment remain unexplored. Objective: To investigate the correlations of serum levels of matrix metalloproteinase-2 (MMP-2), MMP-3, and MMP-9 with CAA-related MRI markers, ICH recurrence, and cognitive status. Methods: 68 cases with first probable CAA-ICH and 69 controls were recruited. Clinical and imaging data were obtained at baseline and serum MMPs in the acute phase were measured by Luminex multiplex assays. Cognitive status was assessed with the Chinese version of Mini-Mental State Examination within 10–14 days after ICH onset. Results: Serum MMP-2 level was significantly lower in CAA-ICH patients than controls while MMP-9 was significantly higher. In CAA-ICH patients, MMP-3 level was significantly associated with lobar cerebral microbleeds count after adjusting age, sex, and hypertension (adjusted coefficient 0.368, 95%CI 0.099–0.637, p = 0.008). During a median follow-up of 2.4 years, higher level of MMP-2 predicted lower CAA-ICH recurrence after adjusting age (adjusted HR 0.326, 95%CI 0.122–0.871, p = 0.025), ICH volume (adjusted HR 0.259, 95%CI 0.094–0.715, p = 0.009), total MRI burden of SVD score (adjusted HR 0.350, 95%CI 0.131–0.936, p = 0.037) respectively. Besides, higher level of MMP-2 was significantly associated with decreased risk of cognitive impairment independent of age and ICH volume (adjusted OR 0.054, 95%CI 0.005–0.570, p = 0.015). Conclusion: Serum MMP-2 in acute phase might be a promising biomarker to predict CAA-ICH recurrence and to evaluate the risk of cognitive impairment.

Cardiovascular diseases are the leading cause of death worldwide. Cardiomyocytes are capable of coordinated contractions, which are mainly responsible for pumping blood. When cardiac stress occurs, cardiomyocytes undergo transition from physiological homeostasis to hypertrophic growth, proliferation, or apoptosis. During these processes, many cellular factors and signaling pathways participate. PTEN is a ubiquitous dual-specificity phosphatase and functions by dephosphorylating target proteins or lipids, such as PIP3, a second messenger in the PI3K/AKT signaling pathway. Downregulation of PTEN expression or inhibiting its biologic activity improves heart function, promotes cardiomyocytes proliferation, reduces cardiac fibrosis as well as dilation, and inhibits apoptosis following ischemic stress such as myocardial infarction. Inactivation of PTEN exhibits a potentially beneficial therapeutic effects against cardiac diseases. In this review, we summarize various strategies for PTEN inactivation and highlight the roles of PTEN-less in regulating cardiomyocytes during cardiac development and stress responses.

Globally, the installed capacity of photovoltaic (PV) power plants is undergoing rapid growth. However, the random output power fluctuation of PV plants has brought great challenge to power system stable operation. One of the most effective approaches to counteract the impact of power fluctuation is to carry out power forecasting under ultra-short-term scales, among which the second-level power forecasting technique is still absent since the pure historical data analysis of PV plant output power cannot deal with the sudden output power change induced by moving cloud and the traditional cloud image detection methods actually fail to achieve accurate PV power forecasting in high temporal and spatial resolutions. This article proposes an inverter-data-driven method to achieve the second-level PV power forecasting. In specific, multilayer feed-forward artificial neural network based on the error back propagation algorithm is applied to first establish the mapping relations from shading conditions of PV array to its corresponding output power. Combining with output power of neighboring PV arrays as well as their geographical location information, the shading conditions of those shaded PV array can be reversely deduced. And then, the deduced shading conditions of all PV arrays will be converted into one virtual cloud image to identify the instant cloud characteristics. In consequence, the consecutively generated virtual cloud images can depict the moving direction, speed, and shape of shading cloud and then help easily realize the second-level power forecasting of PV plant. Case study and experimental results verified the performance of the proposed method.

Sm3+ doped KSr2Nb5O15 (KSN-Sm) textured ceramics with anisotropic photochromic and luminescence modulation behaviors provided a new strategy for the enhancement of anti-counterfeiting ability. The KSN-Sm textured ceramics were fabricated by the tape casting technology, which exhibited obvious grain-orientation, with Lotgering factor f(00l) of 0.62. The textured sample possessed evident difference of reflectivity, photochromic, luminescent and luminescence modulation properties among various grain-orientated directions. The difference of luminescent emission intensity was over than 30 % and the luminescence modulation ratios △Rt are 75.3 % and 63.3 % along paralleled and vertical [00l] orientations, respectively. These optical anisotropies were attributed to the different refractive indexes, distributions of photochromic centers and energy transfer rates at various orientations. This work is hopeful to achieve the multidirectional data recording and enhancement of anti-counterfeiting ability of photochromic ceramics by the anisotropic properties of textured ceramics.

Liquid nitrogen (LN2) cooling can induce significant cracking damage in coalbed methane (CBM) reservoirs. To investigate the combined effects of LN2 cooling and bedding angles on the mechanical behaviors of bedded coal, coal specimens with different bedding angles (0°, 30°, 60° and 90°) were cooled. The variations in the surface features and P-wave velocity of the specimens were analyzed. The mechanical properties (tensile strength, peak strain and absorbed energy) were measured under Brazilian test conditions and compared. Furthermore, the crack propagation processes and the failure mechanisms were observed and compared. The results showed that LN2 cooling can induce considerable thermal damage inside the coal, resulting in the deterioration of the coal’s mechanical properties. This deterioration led to easier cracking and a higher fragmentation degree under splitting load. In addition, the reductions in tensile strength, peak strain and absorbed energy exhibited obvious anisotropic characteristics. The thermal cracks induced by LN2 cooling participated in the formation of macrocracks. After LN2 cooling, the failure mode remained unchanged from that before cooling at bedding angles of 0°, 30° and 90°. Notably, a transition from mixed-mode failure (primarily caused by tensile failure) to tensile failure occurred at the 60° bedding angle. This transition caused the specimen to fail at a relatively lower load, resulting in maximum reductions in tensile strength (34.8%), peak strain (27.6%) and absorbed energy (55.0%) at the 60° bedding angle. This paper provides new insights into the LN2 fracturing of bedded coal seams.

This work aimed to explore the relationship between spine surgery lumbar facet joint (LFJ) and lumbar disc herniation (LDH) via compressed sensing algorithm-based MRI images to analyze the clinical symptoms of patients with residual neurological symptoms after LDH. Under weighted BM3D denoising, Epigraph method was introduced to establish the novel CSMRI reconstruction algorithm (BEMRI). 127 patients with LDH were taken as the research objects. The BEMRI algorithm was compared with others regarding peak signal-to-noise ratio (PSNR) and structural similarity index (SSIM). Patients’ bilateral LFJ angles were compared. The relationships between LFJ angles, lumbar disc degeneration, and LFJ degeneration were analyzed. It turned out that the PSNR and SSIM of BEMRI algorithm were evidently superior to those of other algorithms. The proportion of patients with grade IV degeneration was at most 31.76%. Lumbar disc grading was positively correlated with change grading of LFJ degeneration ( P < 0.001 ). LFJ asymmetry was positively correlated with LFJ degeneration grade and LDH ( P < 0.001 ). Incidence of residual neurological symptoms in patients aged 61–70 years was as high as 63.77%. The proportion of patients with severe urinary excretion disorders was 71.96%. Therefore, the BEMRI algorithm improved the quality of MRI images. Degeneration of LDH was positively correlated with degeneration of LFJ. Asymmetry of LFJ was notably positively correlated with the degeneration of LFJ and LDH. Patients aged 61–70 years had a high incidence of residual neurological symptoms after surgery, most of which were manifested as urinary excretion disorders.

Introduction The mammalian target of rapamycin (mTOR) is a downstream mediator in the phosphatidylinositol 3-kinase/Akt signaling pathway, and plays a central role in cell proliferation, growth, differentiation, migration, and survival. Temsirolimus (CCI-779), a selective inhibitor of the mTOR, is an ester analog of rapamycin (sirolimus) with improved aqueous solubility and pharmacokinetic (PK) properties. Preclinical studies have confirmed additive and synergistic antitumor activity in cancer cell lines (breast, prostate cancer) with combinations of taxanes and mTOR inhibitors. We conducted a phase I open-label, dose-escalation study to determine the maximal tolerated dose (MTD) of docetaxel in combination with temsirolimus in patients with refractory solid tumors. Patients and methods Eligible patients had a diagnosis of a refractory solid malignancy, measurable disease, and adequate organ function. Patients were sequentially enrolled in 4 dose level intravenous combinations of docetaxel and temsirolimus. Temsirolimus was administered weekly with docetaxel administered every 3 weeks. Laboratory data for tumor markers and radiologic imaging were conducted prestudy and then after every 2 cycles of the treatment. Radiologic response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Blood samples for PK and pharmacodynamic analysis were planned to be drawn at MTD. Apart from the traditional 3+3 design, we also implemented Bayesian Optimal Interval design which uses isotonic regression method to select MTD. We proceeded with isotonic regression analysis by using 20% dose-limiting toxicity (DLT) rate as target. Results Twenty-six patients were treated in this study in 4 cohorts and dose levels. Fourteen males and 12 females were enrolled with a median age of 50 years (range of 27 to 72 y) and median Eastern Cooperative Oncology Group performance score of 1. Tumor histologies included pancreas (6), colon (5), rectum (3), gallbladder (2), non-small cell lung (2), endometrium (1), neuroendocrine (1), esophagus (1), stomach (1), pharynx (1), small intestine (1), and duodenum (1). Stable disease was observed in 2/4 (50%), 3/7 (43%), 4/10 (40%), and 3/5 (60%) patients in cohorts 1, 2, 3, and 4, respectively. Dose escalation in cohorts 2, 3, and 4 was complicated by DLTs such as grade 4 neutropenia and grade 3 diarrhea and an inability for patients to tolerate treatments during and beyond cycle 1 without dose reductions. Therefore, we could not determine an MTD or recommended phase II dose using the traditional 3+3 study analysis. Blood samples for PK and pharmacodynamic analysis were not collected since MTD was not determined. By using 20% DLT rate closest to the target, isotonic regression analysis showed identical estimated DLT rates in dose -1 (docetaxel 50 mg/m2 and temsirolimus 15 mg/m2) and dose level 1 (docetaxel 60mg/m2 and temsirolimus 15 mg/m2). Conclusions Dose escalation of docetaxel and temsirolimus was limited by severe myelosuppressive toxicity in this phase I study. Most of the DLTs occurred after cycle 1 of therapy hence, we were unable to determine MTD or collect blood samples for PK and pharmacodynamic analysis. Our trial did not meet its objectives due to significant DLTs with this chemotherapy combination. Although our novel use of Bayesian Optimal Interval design using isotonic regression method to select MTD showed identical estimated DLT rates in dose levels 1 and -1, clinically our patients were not able to complete 2 cycles of this regimen without dose reductions due to myelosuppressive toxicity in either of these dose levels, and hence, escaped clinical validity. This combination regimen should not be studied further at the dose levels and schedules tested in our study.