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Abstract Power system unreliability tracing model allocates the system's reliability index to individual components, identifying potential weaknesses. This study expands its scope by considering the impact of storage resources. Unreliable factors leading to load shedding are categorized into two groups: objective factors inherent to the component and insufficient storage resources. The latter requires a retrospective analysis of other components that caused unreliability previously. When allocating responsibility for load shedding at a certain time, it begins by allocating it among components based on differences between fixed expected output and actual supply. Expected output insufficiency is considered as the unreliable factor. This insufficiency due to insufficient storage resources is then decomposed into segments, each caused by excessive output in earlier instances of the same component. The expected output excess is attributed to the expected output insufficiency of other components in previous times, for which responsibility has been allocated to each component. Consequently, the expected output insufficiency at a particular time can be traced back based on a temporal recursive model, with the load shedding further allocated to components before that time. Case studies based on several systems demonstrate that the proposed model's allocation results are reasonable and more accurate than the traditional model.

Abstract Background The therapeutic potential of immune checkpoint blockade (ICB) extends across various cancers; however, its effectiveness in treating hepatocellular carcinoma (HCC) is frequently curtailed by both inherent and developed resistance. Objective This research explored the effectiveness of integrating anlotinib (a broad‐spectrum tyrosine kinase inhibitor) with programmed death‐1 (PD‐1) blockade and offers mechanistic insights into more effective strategies for treating HCC. Methods Using patient‐derived organotypic tissue spheroids and orthotopic HCC mouse models, we assessed the effectiveness of anlotinib combined with PD‐1 blockade. The impact on the tumour immune microenvironment and underlying mechanisms were assessed using time‐of‐flight mass cytometry, RNA sequencing, and proteomics across cell lines, mouse models, and HCC patient samples. Results The combination of anlotinib with an anti‐PD‐1 antibody enhanced the immune response against HCC in preclinical models. Anlotinib remarkably suppressed the expression of transferrin receptor (TFRC) via the VEGFR2/AKT/HIF‐1α signaling axis. CD8+ T‐cell infiltration into the tumour microenvironment correlated with low expression of TFRC. Anlotinib additionally increased the levels of the chemokine CXCL14, crucial for attracting CD8+ T cells. CXCL14 emerged as a downstream effector of TFRC, exhibiting elevated expression following the silencing of TFRC. Importantly, low TFRC expression was also associated with a better prognosis, enhanced sensitivity to combination therapy, and a favourable response to anti‐PD‐1 therapy in patients with HCC. Conclusions Our findings highlight anlotinib's potential to augment the efficacy of anti‐PD‐1 immunotherapy in HCC by targeting TFRC and enhancing CXCL14‐mediated CD8+ T‐cell infiltration. This study contributes to developing novel therapeutic strategies for HCC, emphasizing the role of precision medicine in oncology. Highlights Synergistic effects of anlotinib and anti‐PD‐1 immunotherapy demonstrated in HCC preclinical models. Anlotinib inhibits TFRC expression via the VEGFR2/AKT/HIF‐1α pathway. CXCL14 upregulation via TFRC suppression boosts CD8+ T‐cell recruitment. TFRC emerges as a potential biomarker for evaluating prognosis and predicting response to anti‐PD‐1‐based therapies in advanced HCC patients.

Abstract The increase in wind power penetration leads to the risk of energy supply interruption in integrated electricity‐heat energy systems (IHES). This paper presents an analytical‐based approach for the efficient operational reliability evaluation of the IHES. The wind power distribution characteristic model considering correlation is constructed based on Hidden Markov Model (HMM). To reduce computational complexity, a critical system state identification (CSSI) method is proposed that characterises both random device failures and wind power uncertainty. Under each critical system state, the analytical function relationship between the reliability index and the uncertainty factors is established based on the virtual stochastic response surface (VSRS) method. The analytical function can directly calculate the reliability index when the wind power output varies, avoiding a large number of repeated calculations of the optimal load‐shedding model of the system and reducing the time required for reliability assessment. This allows the operator to evaluate the operational reliability of the integrated energy system in real‐time. The numerical simulation of the test system combining the IEEE 33‐node distribution system and the existing 28‐node heating system proves the effectiveness of the proposed method.

Abstract Power outages in urban area carry heavy social and economic costs. Although social cost, especially public sentiment, is concerned by engineers and managers, it has been only qualitatively investigated without a rigorous model in the state‐of‐the‐art research and practice of service restoration (SR) for a long time. To fill this gap, this paper investigates a hybrid model which takes public sentiment into consideration by quantifying public sentiment triggered by power outage. Furthermore, conventional SR method focused on the optimization model with ideal conditions, which leaves a large room for improvement in complex environment. To improve the robustness of the model, the authors propose a reinforcement learning framework to analyze emergency management process without prior rules. At each time step, the optimal decision can be made automatically by a learned model. The numerical simulations with modified IEEE 33‐bus and IEEE 123‐bus systems demonstrate the effectiveness of the proposed method.

Abstract Purpose The purpose of this study was to test the hypothesis that brain white matter hyperintensities (WMH) are more common in patients receiving epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI) and identify clinical risk factors associated with WMH. Experimental design This multiple‐center, prospective cohort study was conducted from March 2017 to July 2020. Two groups of patients with non‐small cell lung cancer (NSCLC) who received or did not receive EGFR‐TKI were included and followed up for more than 24 months. The progression of WMH was defined as an increase of ≥1 point on the Fazekas visual rating scale between the baseline and at the 2‐year follow‐up. A modified Poisson regression model was performed to evaluate risk factors on increased WMH load. Results Among 286 patients with NSCLC, 194 (68%) patients with NSCLC who received EGFR‐TKI and 92 (32%) patients with NSCLC without EGFR‐TKI treatment were analyzed. Modified Poisson regression analysis showed that EGFR‐TKI treatment was independently associated with the WMH progression (EGFR‐TKI: aRR 2.72, 95% confidence interval [CI] 1.46–5.06, p = .002). Interleukin (IL)‐2, IL‐4, and IL‐10 were associated with increased WMH in the adjusted model (IL‐2: aRR 1.55 [95% CI 1.06–2.25], p = .023; IL‐4: aRR 1.66 [95% CI 1.13–2.43], p = .010; IL‐10: aRR 1.48 [95% CI 1.06–2.06], p = .020). Conclusion Patients with NSCLC who received EGFR‐TKI may be at higher risk of developing WMH or worsening of WMH burden. The impact of increased WMH lesions in these patients is to be further assessed. IL‐2, IL‐4, and IL‐10 may be used as potential biomarkers to monitor the risk of increased WMH burden

Abstract The method of fundamental solutions with excitation source (MFS‐ES) is a reliable method for determining the eigenvalues of a two‐dimensional hollow waveguide. However, the accuracy in MFS‐ES is extremely dependent on the choice of the auxiliary boundary. In this work, to avoid the problem, a regularized MFS‐ES (RMFS‐ES) is proposed. First, to overcome the shortcomings of MFS, a regularized method of fundamental Solutions (RMFS) is proposed by borrowing the ideas of singular boundary method (SBM) and single layer regularized meshless method (SRMM). Second, the expressions for the fundamental solutions at the singularities are given by utilizing the subtraction and adding‐back technique (SAB). Third, the excitation source method is introduced to overcome the problem that the RMFS may also have spurious frequencies. Finally, to improve the accuracy of RMFS‐ES in solving polygonal waveguide eigenvalue, a wedge scheme (WS) is given. Numerical results show that the meshless RMFS‐ES is a promising numerical method for waveguide eigenvalue problems.

Abstract Real batteries used for the performance testing and evaluation of the drive systems of electric vehicles (EVs) are being replaced by battery emulators (BEs) because of the high test costs, long test cycles, and difficulty in adapting to extreme operating conditions associated with the use of real batteries. A parametric BE for a lithium‐ion battery based on a voltage source converter is presented. First, a Thevenin model of the battery is established, and a parameter identification method is proposed to obtain the relationship between the parameters of the battery model and the characteristics of the external electrical port (i.e. I–V characteristics) of the battery. Subsequently, based on the I–V characteristics, the topological structure of the power electronic device of the BE is designed, and the working modes under charging and discharging conditions are presented. Finally, an experimental prototype of the BE is designed and tested. The experimental results show that the proposed BE power converter can successfully simulate the external port voltage and current characteristics of the battery, which can replace the real battery to provide an effective test environment for the test and evaluation of the electric drive system of EVs.

Abstract Objective To investigate the clinical effect of butylphthalide combined with urinary kallidinogenase in the treatment of chronic cerebral circulatory insufficiency (CCCI). Methods A total of 102 CCCI patients admitted to our hospital from October 2020 to December 2021 were retrospectively enrolled in this study. According to the different therapeutic strategy, the patients were divided into combined group (treated with butylphthalide combined with urinary kallidinogenase, n = 51) and butylphthalide group (treated with butylphthalide, n = 51). Blood flow velocity and cerebral blood flow perfusion before and after treatment between the two groups were compared. The clinical efficacy and adverse events of the two groups were analyzed. Results After treatment, the effective rate of the combined group was significantly higher than the butylphthalide group (p = .015). Before treatment, the blood flow velocity of middle cerebral artery (MCA), vertebral artery (VA), basilar artery (BA) were comparable (p > .05, respectively), while after treatment, the blood flow velocity of MCA, VA, and BA in combined group were faster than those in butylphthalide group (p .05, respectively). After treatment, rCBF and rCBV in combined group were higher than those in butylphthalide group (p

Abstract Food production is one of the main contributors to greenhouse gas emissions and climate change. China, as a rapidly developing economy, contributes to an unsustainable food system as its consumption of animal products and meat has continued to grow in recent decades. Using the extended theory of planned behavior as the conceptual framework, this paper examines factors influencing consumers' intention to purchase sustainable food in China. To this end, a population‐based face‐to‐face survey was conducted with 2422 respondents in five provinces spanning the north and south of China. The results showed that the traditional constructs of behavioral attitude, subjective norms, perceived behavioral control, and the additional construct of perceived quality are significant in inducing such intentions. This paper suggests that to enhance consumers' willingness to shift to sustainable food consumption, appropriate regulation and monitoring framework is needed to increase consumers' trust toward sustainable food. The government can also cooperate with the media, experts, and social media opinion leaders to ensure that messages on sustainable development are promoted in effective ways.

Surgery is the most important treatment for perianal abscesses. However, the gut microbiota of patients with perianal abscess and the effects of perianal abscess on the gut microbiota after surgery are unknown. In this study, significant changes in interleukin 6 and tumor necrosis factor-α in the blood of healthy subjects, patients with perianal abscesses, and patients after perianal abscess surgery were identified. 16S rRNA gene sequencing technology was used to detect the changes in the gut microbiota among 30 healthy individuals and 30 patients with perianal abscess before and after surgery. Venn diagrams and alpha diversity analyses indicated differences in the abundance and uniformity of gut microbiota between the healthy individuals and patients with perianal abscesses before and after surgery. Beta diversity analysis indicated that the grouping effects among the control, abscess, and surgery groups were good. The classification and compositional analysis showed significant differences in the gut microbiota between healthy individuals and patients with perianal abscesses before and after surgery. LEfSe analysis, random forest analysis, and ROC curve analysis showed that Klebsiella (AUC=0.7467) and Bilophila (AUC=0.72) could be potential biomarkers for the diagnosis of perianal abscess. The functional prediction results showed that the differential microbiota is significantly enriched in the pathways related to nutrition and drug metabolism. This study may have important implications for the clinical management and prognostic assessment of patients with perianal abscesses.

Abstract Diabetic retinopathy (DR) is the leading cause of vision loss in working age population. Intravitreal injection of anti‐VEGF antibody is widely used in clinical practice. However, about 27% of patients show poor response to anti‐VEGF therapy and about 50% of these patients continue to have macular thickening. Frequent intravitreal injections of antibody may increase the chance of endophthalmitis and cause visual loss or even blindness once happened. Therefore, there is a greatly urgent need for novel noninvasive target to treat DR clinically. Here, the formulation of a smart supramolecular peptide (SSP) eye drop for DR treatment that is effective via specifically identifying and capturing soluble semaphorin 4D (sSema4D), a strongly pro‐angiogenesis and exudates factor, is reported. The SSP nanostructures encapsulate sSema4D so that all biological effects mediated by three receptors of sSema4D are inhibited, thereby significantly alleviating pathological retinal angiogenesis and exudates in DR. Moreover, it is found that combination of SSPs eye drop and anti‐VEGF injection shows better therapeutic effect over anti‐VEGF treatment alone. Overall, SSP eye drop provide an alternative and effective method for noninvasive treatment for DR.

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.

Abstract Sensory nerves are long being recognized as collecting units of various outer stimuli; recent advances indicate that the sensory nerve also plays pivotal roles in maintaining organ homeostasis. Here, this study shows that sensory nerve orchestrates intervertebral disc (IVD) homeostasis by regulating its extracellular matrix (ECM) metabolism. Specifically, genetical sensory denervation of IVD results in loss of IVD water preserve molecule chondroitin sulfate (CS), the reduction of CS bio‐synthesis gene chondroitin sulfate synthase 1 (CHSY1) expression, and dysregulated ECM homeostasis of IVD. Particularly, knockdown of sensory neuros calcitonin gene‐related peptide (CGRP) expression induces similar ECM metabolic disorder compared to sensory nerve denervation model, and this effect is abolished in CHSY1 knockout mice. Furthermore, in vitro evidence shows that CGRP regulates nucleus pulposus cell CHSY1 expression and CS synthesis via CGRP receptor component receptor activity‐modifying protein 1 (RAMP1) and cyclic AMP response element‐binding protein (CREB) signaling. Therapeutically, local injection of forskolin significantly attenuates IVD degeneration progression in mouse annulus fibrosus puncture model. Overall, these results indicate that sensory nerve maintains IVD ECM homeostasis via CGRP/CHSY1 axis and promotes IVD repair, and this expands the understanding concerning how IVD links to sensory nerve system, thus shedding light on future development of novel therapeutical strategy to IVD degeneration.

Circulating tumor cell (CTC) analysis holds great potential to be a noninvasive solution for clinical cancer management. A complete workflow that combined CTC detection and single‐cell molecular analysis is required. We developed the ChimeraX®‐i120 platform to facilitate negative enrichment, immunofluorescent labeling, and machine learning‐based identification of CTCs. Analytical performances were evaluated, and a total of 477 participants were enrolled to validate the clinical feasibility of ChimeraX®‐i120 CTC detection. We analyzed copy number alteration profiles of isolated single cells. The ChimeraX®‐i120 platform had high sensitivity, accuracy, and reproducibility for CTC detection. In clinical samples, an average value of > 60% CTC‐positive rate was found for five cancer types (i.e., liver, biliary duct, breast, colorectal, and lung), while CTCs were rarely identified in blood from healthy donors. In hepatocellular carcinoma patients treated with curative resection, CTC status was significantly associated with tumor characteristics, prognosis, and treatment response (all P

Abstract One of the imperative medical requirements for cancer treatment is how to establish an imaging‐guided nanocarrier that combines therapeutic and imaging agents into one system. siRNA therapeutics have shown promising prospects in controlling life‐threatening diseases. However, it is still challenging to develop siRNA formulations with excellent cellular entry capability, efficient endosomal escape, and simultaneous visualization. Herein, we fabricated multifunctional ionizable lipid nanoparticles (iLNPs) for targeted delivery of siRNA and MRI contrast agent. The iLNPs comprises DSPC, cholesterol, PEGylated lipid, contrast agent DTPA‐BSA (Gd), and ionizable lipid termed iBL0104. siRNA‐loaded iLNPs (iLNPs/siRNA) could be decorated with a tumor targeting cyclic peptide (c(GRGDSPKC)) (termed GARP), or without targeting modification (termed GAP). Data revealed that GARP/siRNA iLNPs exhibited significantly higher cellular entry efficiency than GAP/siRNA iLNPs. GARP/siRNA iLNPs rapidly and effectively escaped from endosome and lysosome after internalization. Compared with GAP/siPLK1, GARP/siPLK1 exhibited better tumor inhibition efficacy in both cell‐line derived xenograft and liver cancer patient derived xenograft murine models. In addition, GARP formulation displayed ideal MRI effect in tumor‐bearing mice, and was well tolerated by testing animals. Therefore, this study provides an excellent example for achieving imaging‐guided and tumor‐targeted siRNA delivery and cancer treatment, highlighting its promising potential for translational medicine application.

Background Intracerebral hemorrhage is the most disabling and lethal form of stroke. We aimed to develop a novel clinical score for neurological deterioration during hospitalization after intracerebral hemorrhage. Methods and Results We analyzed data from the CHERRY (Chinese Cerebral Hemorrhage: Mechanism and Intervention) study. Two‐thirds of eligible patients were randomly allocated into the training cohort (n=1027) and one‐third into the validation cohort (n=515). Multivariable logistic regression was used to identify factors associated with neurological deterioration (an increase in National Institutes of Health Stroke Scale of ≥4 or death) within 15 days after symptom onset. A prediction score was developed based on regression coefficients derived from the logistic model. The site, size, gender, National Institutes of Health Stroke Scale, age, leukocyte, sugar (SIGNALS) score was developed as a sum of individual points (0–8) based on site (1 point for infratentorial location), size (3 points for >20 mL of supratentorial hematoma volume or 2 points for >10 mL of infratentorial hematoma volume), sex (1 point for male sex), National Institutes of Health Stroke Scale score (1 point for >10), age (1 point for ≥70 years), white blood cell (1 point for>9.0×109/L), and fasting blood glucose (1 point>7.0 mmol/L). The proportion of patients who suffered from neurological deterioration increased with higher SIGNALS score, showing good discrimination and good calibration in the training cohort (C statistic, 0.821; Hosmer‐Lemeshow test, P=0.687) and in the validation cohort (C statistic, 0.848; Hosmer‐Lemeshow test, P=0.592), respectively. Conclusions The SIGNALS score reliably predicts the risk of in‐hospital neurological deterioration of patients with intracerebral hemorrhage.

Objective To investigate the methods and outcomes of hip arthroscopy for hip labrum calcification, and to discuss the clinical, imaging, and intraoperative findings of hip labrum calcification. Methods This is a therapeutic case series study. From January 2015 to June 2018, 15 patients who met the inclusion and exclusion criteria were followed up for at least 2 years for an analysis on the outcomes of arthroscopy in the treatment of hip labrum calcification and the clinical, imaging, and intraoperative findings of the patients. There were eight males and seven females, with an average age of 38.9 ± 8.8 years (range, 23–50 years). The visual analog scale (VAS), the modified Harris hip score (mHSS), and the international hip outcome tool (iHOT‐12) were used to evaluate the outcomes of surgery. Results A total of 15 patients were followed up for at least 2 years (28.1 ± 2.9 months). The average calcified volume was 118.0 mm3 (range, 19.4–609.2 mm3) and calcified volume was related to the preoperative hip function score. Thirteen patients had pain in the groin area (86.7%). Labrum calcifications were located (according to the clock distribution) as follows: 14 patients were anterior and superior (11:00–3:00); 12 cases of femoroacetabular impingement (FAI) were observed during operation, including five cases of pincer type, two cases of cam type, and five cases of mixed type. VAS pain score means were 7.73 ± 1.28 before surgery, decreasing to 2.0 ± 0.89 and 1.73 ± 0.79 at 1 and 2 years post‐surgery, respectively. mHSS scores were 57.40 ± 6.23 before surgery and 82.10 ± 4.76 and 83.18 ± 4.07, 1 and 2 years post‐surgery, respectively; iHOT‐12 mean score pre‐surgery was 37.67 ± 4.85, increasing to 67.64 ± 5.30 and 72.18 ± 4.49, 1 and 2 years post‐surgery, respectively. Compared with preoperative values, postoperative VAS, mHSS, and iHOT‐12 scores were significantly improved (P

Abstract Background Hepatocellular carcinoma (HCC) is a prevalent malignancy with poor prognosis. As a cell adhesion molecule, poliovirus receptor (PVR/CD155) is abnormally overexpressed in tumour cells, and related to tumour proliferation and invasion. However, the potential role and mechanism of CD155 have not yet been elucidated in HCC. Methods Immunohistochemistry, RT‐PCR and Western blot assays were used to determine CD155 expression in HCC cell lines and tissues. Cell Counting Kit‐8 and colony formation assays were used to examine cell proliferation. Transwell and wound healing assays were used to evaluate cell migration and invasion. Cell apoptosis and cycle distribution were assessed by flow cytometry. Cox regression and Kaplan–Meier analyses were performed to explore the clinical significance of CD155. The role of CD155 in vivo was evaluated by establishing liver orthotropic xenograft mice model. RNA sequencing, bioinformatics analysis and co‐immunoprecipitation assay were used to explore the downstream signalling pathway of CD155. Results CD155 was upregulated in HCC tissues and represented a promising prognostic indicator for HCC patients (n = 189) undergoing curative resection. High CD155 expression enhanced cell proliferation, migration and invasion, and contributed to cell survival in HCC. CD155 overexpression also induced epithelial–mesenchymal transition in HCC cells. CD155 function in HCC involved SRC/p38 MAPK signalling pathway. CD155 interacted with SRC homology‐2 domain of SRC and promoted SRC activation, further inhibiting the downstream p38 MAPK signalling pathway in HCC. Conclusions CD155 promotes HCC progression via the SRC/p38 MAPK signalling pathway. CD155 may represent a predictor for poor postsurgery prognosis in HCC patients.

Abstract Background Hepatocellular carcinoma (HCC) is one of the most lethal malignancies. We aimed to identify a robust lipid metabolism‐related signature associated with the HCC microenvironment to improve the prognostic prediction of HCC patients. Methods We analyzed the gene expression profiles of lipid metabolism from Molecular Signatures Database and information of patients from The Cancer Genome Atlas. Gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), and principal component analysis (PCA) were employed for functional annotation. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was employed to verify the expression of model genes in HCC and adjacent tissues. Results As a result, a lipid metabolism‐related signature consisting of acyl‐CoA synthetase long‐chain family member 6 (ACSL6), lysophosphatidylcholine acyltransferase 1, phospholipase A2 group 1B, lecithin‐cholesterol acyltransferase (LCAT), and sphingomyelin phosphodiesterase 4 (SMPD4) was identified among HCC patients. Lysophosphatidylcholine acyltransferase 1, PLA2G1B, and SMPD4 were proved significantly high expression while ACSL6 and LCAT were remarkably low expression in our 15 pairs of matched HCC and normal tissues by qRT‐PCR. Under different conditions, the overall survival (OS) of patients in low‐risk group was prolonged than that in high‐risk group. Moreover, the as‐constructed signature was an independent factor, which was remarkably associated with gender, histologic grade, and platelet level of HCC patients. In addition, the receiver operating characteristic (ROC) curve analysis confirmed the good potency of the model. Functional enrichment analysis further revealed that lower fatty acid (FA) oxidation and higher infiltration of immunocytes were detected in patients from the high‐risk group compared with those in the low‐risk group. Conclusions Our findings indicate that the lipid metabolism‐related signature shows prognostic significance for HCC.

Similarity measures play an important role in many data analysis fields. However, the current cell similarity measures are poor used in data characteristics. Herein, a novel similarity measure named segment weighting similarity (SWS) is developed for the analysis of single‐cell Raman spectra. SWS segments the spectra by the cell biological characteristics and quantifies the significant factors per region, which can increase the contribution of intrinsic biological features and reduce noise. The similarity heat maps of SWS and three other kinds of traditional similarities, including cosine similarity, Pearson correlation coefficient, and Euclidean distance, show that SWS has high accuracy and low bias in distinguishing cell spectra. K‐nearest‐neighbor classifiers have the identification accuracy, sensitivity, and specificity of 0.852, 0.853, and 0.965, respectively. The purity of the clustering model could increase by 0.31 in some tasks of the K‐means and spectral clustering. The classification and clustering results demonstrate that SWS is more effective than common ones. SWS, based on the basic data and intrinsic biological characteristics, provides a new thought and formula in the similarity measure for most of the Raman and infrared technologies, and has great potential for enhancing the performance of machine learning algorithms.

Abstract Introduction COVID‐19 has impacted people with dementia and their family carers, yet little is known about effects on overall quality of life. Methods In a UK cohort study, pre‐ and post‐pandemic data were collected from 114 carers and 93 recently diagnosed people with dementia. Latent growth curve modeling examined change in quality of life. Results Carers reported significant decline in quality of life, although no change was demonstrated by people with dementia. In multivariable analyses, higher levels of cognitive impairment, deprivation, study site, and lower number of memory clinic contacts were associated with greater decline in carer quality of life. Discussion Maintaining life quality for people with dementia during the pandemic appears to have come at the expense of their family carers. This inequity has fallen hardest on those caring for people with more severe dementia, in deprived areas, and with least support from memory services. These effects may be prevented or reversed by post‐diagnostic care.

Hepatitis B virus-related acute liver failure (HBV-ALF) is a common type of liver failure, associated with high short-term mortality and morbidity rates. However, the immune landscape of HBV-ALF and its correlation with cell death are currently unknown. Based on 3 Gene Expression Omnibus data sets, infiltrated immune cells were quantified by single-sample gene set enrichment analysis method. The expression levels of immune genes and the abundance of immune cells in liver failure were compared with those in normal liver. The enrichment scores of cell death gene sets from Kyoto Encyclopedia of Genes and Genomes (KEGG) were calculated by gene set variation analysis method, and a protein-protein interaction (PPI) network was constructed using Cytoscape. Besides 21 differentially expressed immune genes, we identified 11 types of differentially infiltrated immune cells in HBV-ALF compared with normal liver. Enriched pathways of these immune genes mainly consisted of chemokine receptors, chemokine binding, interleukin-10 signaling, and TNFs bind their physiological receptors by Reactome pathway analysis. In addition, the enrichment scores of apoptosis and necroptosis pathway instead of autophagy and ferroptosis were increased in liver failure compared with normal liver. PPI network and gene cluster analysis of immune genes and apoptosis and necroptosis genes suggested that hub genes were mainly related to immune response and apoptosis. In summary, our study offers a conceptual framework to understand the immune landscape of HBV-ALF, which might help to improve prognosis.

Objective To investigate the outcomes of hip arthroscopy for femoroacetabular impingement (FAI) in patients over the age of 50 years. Method This is a therapeutic case series study. A total of 27 FAI patients over the age of 50 years who met inclusion and exclusion criteria and were being followed up for at least 2 years in the orthopaedics department at our hospital between January 2015 and October 2017 were recruited for a prospective analysis on the outcomes of hip arthroscopy. All patients underwent unilateral surgery. Of the patients included, there were 15 men and 12 women, who were aged 50–74 years old (57 ± 6.4 years). The outcomes were assessed using the visual analog scale (VAS), the modified Harris hip score (mHHS), and the International Hip Outcome Tool (iHOT‐12). Results A total of 27 patients were followed up for at least 2 years. The postoperative center‐edge angle, the alpha angle, and the offset decreased significantly compared with preoperative measurements (P

Abstract Background Portal vein tumor thrombus (PVTT) is a common complication in hepatocellular carcinoma (HCC), signaling dismal outcomes. This study was conducted to evaluate the survival benefit of postoperative portal vein perfusion chemotherapy (PVC) in patients with HCC and PVTT. Methods A retrospective review was conducted in 401 consecutive patients with HCC and PVTT who underwent hepatic resection between January 2009 and December 2015 and 67 patients received adjuvant postoperative PVC. A propensity score matching (PSM) was used to match patients with and without PVC at a ratio of 1:1. Results After PSM, the median time to recurrence (TTR) and overall survival (OS) were significantly longer in PVC group compared with control group (12.3 vs 5.8 months, P = .001; 19.0 vs 13.4 months, P = .037; respectively). At 1, 2, 3, and 5 years, the cumulative recurrence rates in PVC group were 48.1%, 86.5%, 92.3% ,96.2%, respectively, with OS rates of 63.8%, 37.9%, 24.4%, 18.3%, respectively; whereas cumulative recurrence rates of 76.6%, 91.5%, 94.3%, and 97.2%, respectively and OS rates of 55.4%, 23.0%, 12.4%, and 12.4%, respectively were recorded for the control group. In multivariate analysis, postoperative PVC emerged as a significant predictor for TTR (hazard ratio [HR], 0.523; P = .001) and OS (HR, 0.591; P = .010). PVC could reduce early recurrence (≤1 year) rate after surgical resection (40.3% vs 64.2%, P = .006) and clinical outcomes were further enhanced by adding sorafenib to postoperative PVC. Conclusions Compared with surgical resection alone, postoperative adjuvant PVC treatment boosts survival and reduces early tumor recurrences in patients surgically treated for HCC and PVTT.

DNA methylation of promoter regions is often associated with epigenetic silencing of gene expression, and DNA methyltransferase (DNMTs) has been used to suppress gene expression. In order to explore the synergistic roles of two methyltransferase members Dnmt3a and Dnmt1, we constructed expression plasmid that could express a recombinant DNMTs consisting of the C‐terminal domains of both Dnmt3a and Dnmt1 fused to a zinc finger domain which binds to the PD‐L1 promoter of human prostate cancer cells (DU145). Programmed death ligand 1 (PD‐L1, B7‐H1, CD‐274) is a transmembrane protein widely expressed on antigen‐presenting and other immune cells. The interaction of PD‐L1 with its receptor PD‐1 is considered an ‘immune checkpoint' for possible cancer therapy. DU145 cells treated with the Dnmt3aC‐1C plasmid showed significantly reduced expression of PD‐L1 as compared to Dnmt3aC or Dnmt1C alone. Our results show that the fusion of Dnmt1 improves the methylation activity of Dnmt3a and enhances its biological functions. This combinatorial strategy can be used to better control PD‐L1 expression to support cytotoxic T lymphocytes (CTL) response against tumors.

Abstract Objective Differentiation‐inducing therapy for tumors is a strategy that aims to induce the differentiation and maturation of cancer stem cells (CSCs). The differentiation‐inducing capacity of arsenic trioxide (ATO) in hepatocellular carcinoma (HCC) and the underlying mechanism were previously unknown. Methods In the present study, we explored the ATO‐induced differentiation of CSCs in HCC by detecting the expression of CSC‐related markers and tumorigenicity variation in vivo and in vitro. We developed a combined chemotherapeutic approach to HCC by characterizing the effects of combinatorial treatment with 5‐fluorouracil (5‐FU)/cisplatin and ATO in vitro and in patient‐derived xenograft models. Changes in gene expression patterns were investigated by gene microarray analysis. Results ATO effectively induced differentiation of CSCs by downregulation of CSC‐related genes and suppression of tumorigenicity capability. Combinatorial treatment with ATO and 5‐FU/cisplatin significantly enhanced therapeutic effects in HCC cells compared with the treatment with 5‐FU/cisplatin alone. Synergistic inhibition of the LIF/JAK1/STAT3 and NF‐kB signaling pathways by ATO and 5‐FU/cisplatin is a potential molecular mechanism underlying the differentiation effect. Conclusions ATO induced the differentiation of HCC CSCs and potentiated the cytotoxic effects of 5‐FU/cisplatin through synergistic inhibition of the LIF/JAK1/STAT3 and NF‐kB signaling pathways. These results offer new insights for the clinical treatment of HCC.

Security issue against different attacks is the core topic of cyberphysical systems (CPSs). In this paper, optimal control theory, reinforcement learning (RL), and neural networks (NNs) are integrated to provide a brief overview of optimal robust control strategies for a benchmark power system. First, the benchmark power system models with actuator and sensor attacks are considered. Second, we investigate the optimal control issue for the nominal system and review the state-of-the-art RL methods along with the NN implementation. Third, we propose several robust control strategies for different types of cyberphysical attacks via the optimal control design, and stability proofs are derived through Lyapunov theory. Furthermore, the stability analysis with the NN approximation error, which is rarely discussed in the previous works, is studied in this paper. Finally, two different simulation examples demonstrate the effectiveness of our proposed methods.

Overlap function is a special type of aggregation function which measures the degree of overlapping between different classes. Recently, complex fuzzy sets have been successfully applied in many applications. In this paper, we extend the concept of overlap functions to the complex-valued setting. We introduce the notions of complex-valued overlap, complex-valued 0-overlap, complex-valued 1-overlap, and general complex-valued overlap functions, which can be regarded as the generalizations of the concepts of overlap, 0-overlap, 1-overlap, and general overlap functions, respectively. We study some properties of these complex-valued overlap functions and their construction methods.

Introduction. Sepsis-induced myocardial dysfunction (SIMD) is the most common complications of sepsis and septic shock with extremely high incidence and mortality. Lipocalin 10 (Lcn10) has recently been identified as a potential biomarker for heart failure, yet its relation to sepsis has not been investigated. The purpose of this study was to explore whether circulating Lcn10 could be used as a prognostic tool in patients with SIMD. Methods. In this single-center observational pilot study, seventy-five sepsis patients were enrolled after sepsis diagnosis or ICU admission (45.3% female, median age 60 years), and 35 patients (46.7%) developed myocardial dysfunction. Serum Lcn10 levels of septic patients were measured using the enzyme-linked immunosorbent assay (ELISA) at the time of admission. Other biomarkers of cardiac function and Lcn10 concentration were compared between SIMD and non-SIMD groups. Results. We observed that the median Lcn10 levels were 2.780 ng/mL in patients with SIMD and 2.075 ng/mL in patients without SIMD (P

Multihop question answering has attracted extensive studies in recent years because of the emergence of human annotated datasets and associated leaderboards. Recent studies have revealed that question answering systems learn to exploit annotation artifacts and other biases in current datasets. Therefore, a model with strong interpretability should not only predict the final answer, but more importantly find the supporting facts’ sentences necessary to answer complex questions, also known as evidence sentences. Most existing methods predict the final answer and evidence sentences in sequence or simultaneously, which inhibits the ability of models to predict the path of reasoning. In this paper, we propose a dual-channel reasoning architecture, where two reasoning channels predict the final answer and supporting facts’ sentences, respectively, while sharing the contextual embedding layer. The two reasoning channels can simply use the same reasoning structure without additional network designs. Through experimental analysis based on public question answering datasets, we demonstrate the effectiveness of our proposed method

Grouping function is a special kind of aggregation function which measures the amount of evidence in favor of either of the two choices. Recently, complex fuzzy sets have been successfully used in many fields. This paper extends the concept of grouping functions to the complex-valued setting. We introduce the concepts of complex-valued grouping, complex-valued 0-grouping, complex-valued 1-grouping, and general complex-valued grouping functions. We present some interesting results and construction methods of general complex-valued grouping functions.

Abstract Rationale CD13 is a new marker for liver cancer stem cells (CSCs) that contributes to sorafenib resistance in hepatocellular carcinoma (HCC). However, the underlying mechanism of CD13 in HCC sorafenib resistance remains enigmatic. Methods The expression of CD13 in HCC cell lines and tissues was assayed by RT‐PCR, western‐blot, and immunohistochemistry staining. Athymic BALB/c nu/nu mice model was used to study the in vivo functions of CD13. Clinical significance of CD13 was evaluated by Kaplan‐Meier methods. Cellular proliferation rate was evaluated by cell counting kit‐8 cell proliferation assay and colony formation assay. Tunel assay was used to detect cell death ratio. Transwell assay was used to evaluate the motility of cells. Immunoprecipitation (IP), liquid chromatography‐mass spectrometry (LC‐MS)/MS, and co‐IP were applied to investigate potential protein interactions of CD13. Results In this research, we found that CD13 expression was higher in metastatic HCC samples, and its overexpression was predicted worse prognosis for patients after surgical resection. Functionally, CD13 promoted HCC proliferation, invasion, cell cycle progression as well as sorafenib resistance. Mechanistically, CD13 interacted with histone deacetylase5 (HDAC5) to promote its protein stability, thus resulting in HDAC5‐mediated lysine‐specific demethylase 1 (LSD1) deacetylation and protein stabilization. Consequently, LSD1 decreased the NF‐κB catalytic unit p65 methylation that led to p65 protein stability. A CD13 inhibitor ubenimex in combination with sorafenib, suppressed the tumor growth and attenuated the resistance of HCC cells toward sorafenib in patient‐derived xenograft models. Conclusions CD13 promotes HCC progression and induces sorafenib resistance, mainly via interacting with HDAC5 to prevent the degradation of p65 and activate NF‐kB signaling pathway. CD13 is a prognostic indicator for HCC patients underwent curative resection as well as a predictor of response to treatment with sorafenib. Our study establishes the new therapeutic potential of targeting CD13‐HDAC5‐LSD1‐NF‐κB in HCC.

Abstract Background High rates of postoperative tumor recurrence contribute to poor outcome in hepatocellular carcinoma (HCC). Here, we investigated whether circulating tumor cells (CTCs) status can predict the benefit of adjuvant transcatheter arterial chemoembolization (TACE) in patients with HCC. Methods The retrospective study enrolled 344 HCC patients with preoperative CTCs analysis. Clinical outcomes including recurrence and survival were compared between those who received and who did not receive adjuvant TACE. Similar comparisons were made for patients stratified according to CTC status (CTC‐negative [CTC = 0], n = 123; CTC‐positive [CTC ≥ 1], n = 221). Propensity score matching (PSM) strategy was adopted to offset differences between two groups. Results In the study cohort as a whole or in CTC‐negative cohort, there were no observable differences in overall survival (OS) or time to recurrence (TTR) between TACE and control group (P > .05). In CTC‐positive patients, PSM generated 64 patient pairs, and patients with adjuvant TACE had significantly better clinical outcomes (OS: not reached vs 36.4 months, P

Signal regulatory protein α (SIRPα), a transmembrane protein that is predominantly expressed in dendritic cells (DCs) or macrophages, interacts with CD47 that is overexpressed in almost all types of tumor cells. The interaction between SIRPα and CD47 leads to a negative signal that prevents the phenotypic and functional maturation of DC and inhibits phagocytosis. The SIRPα knockdown in DCs that were pulsed with a modified HPV16E7 (HPV16mE7) protein with enhanced antigenicity and reduced transformation activity results in increased cytokine (TNF-α/IL-12/IL-6) secretion, IFN-γ secretion by T lymphocytes, and in vitro/in vivo tumoricidal activity against cervical cancer cells. Taken together, these results suggest that SIRPα-silenced DC vaccination presented potential therapeutic implications against cervical cancer.

Background. Sudden sensorineural hearing loss (SSNHL) is an otologic emergency and could lead to social difficulties and mental disorders in some patients. Although many studies have analyzed altered brain function in populations with hearing loss, little information is available about patients with idiopathic SSNHL. This study is aimed at investigating brain functional changes in SSNHL via functional magnetic resonance imaging (fMRI). Methods. Thirty-six patients with SSNHL and thirty well-matched normal hearing individuals underwent resting-state fMRI. Amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and functional connectivity (FC) values were calculated. Results. In the SSNHL patients, ALFF and fALFF were significantly increased in the bilateral putamen but decreased in the right calcarine cortex, right middle temporal gyrus (MTG), and right precentral gyrus. Widespread increases in FC were observed between brain regions, mainly including the bilateral auditory cortex, bilateral visual cortex, left striatum, left angular gyrus (AG), bilateral precuneus, and bilateral limbic lobes in patients with SSNHL. No decreased FC was observed. Conclusion. SSNHL causes functional alterations in brain regions, mainly in the striatum, auditory cortex, visual cortex, MTG, AG, precuneus, and limbic lobes within the acute period of hearing loss.

System security is essential for the operation of the island microgrid. However, the system security is generally threatened due to the presence of physical uncertainties and cyber attacks. In this article, a novel sliding mode load control strategy is proposed for the microgrid to mitigate cyber attacks and physical uncertainties. Firstly, a high-order disturbance observer (HODO) is designed to estimate the unmeasurable factors in the microgrid. Secondly, a HODO-based sliding mode control (SMC) strategy is proposed where the estimated value observed by the HODO is applied to the sliding mode surface and control law. It can better guarantee the security of the isolated microgrid. Then, the stability of the HODO-based SMC is demonstrated by Lyapunov stability theory. Finally, simulation results show that the proposed control strategy has excellent control performance.

Motion deblurring has been widely studied. However, the relevant quality evaluation of motion deblurred images remains an open problem. The motion deblurred images are usually contaminated by noise, ringing and residual blur (NRRB) simultaneously. Unfortunately, most of the existing quality metrics are not designed for multiply distorted images, so they are limited in predicting the quality of motion deblurred images. In this study, the authors propose a new quality metric for motion deblurred images by measuring NRRB. For a motion deblurred image, the noise level is first estimated. Then the ringing effect is measured by incorporating visual saliency model to adapt to the characteristic of the human visual system. A reblurring‐based method is proposed to extract similarity features between a motion deblurred image and its re‐blurred version for evaluating the residual blur. Finally, the overall quality score of a motion deblurred image is obtained by pooling the scores of noise, ringing and blur. Experimental results conducted on a motion deblurring database demonstrate that the proposed metric significantly outperforms the existing quality metrics. In addition, the proposed NRRB metric is used for improving the existing general‐purpose no‐reference metrics, and very encouraging results are achieved.

Background Endothelial cell injury, induced by dyslipidemia, is the initiation of atherosclerosis, resulting in an imbalance in endothelial fatty acid (FA) transport. Pigment epithelial‐derived factor (PEDF) is an important regulator in lipid metabolism. We hypothesized that PEDF is involved in endothelium‐mediated FA uptake under hyperlipidemic conditions. Methods and Results Circulating PEDF levels were higher in patients with atherosclerotic cardiovascular disease than in normal individuals. However, decreasing trends of serum PEDF levels were confirmed in both wild‐type and apolipoprotein E–deficient mice fed a long‐term high‐fat diet. Apolipoprotein E–deficient/PEDF‐deficient mice were generated by crossing PEDF‐deficient mice with apolipoprotein E–deficient mice, and then mice were fed with 24, 36, or 48 weeks of high‐fat diet. Greater increases in body fat and plasma lipids were displayed in PEDF‐deficient mice. In addition, PEDF deficiency in mice accelerated atherosclerosis, as evidenced by increased atherosclerotic plaques, pronounced vascular dysfunction, and increased lipid accumulation in peripheral tissues, whereas injection of adeno‐associated virus encoding PEDF exerted opposite effects. Mechanistically, PEDF inhibited the vascular endothelial growth factor B paracrine signaling by reducing secretion of protein vascular endothelial growth factor B in peripheral tissue cells and decreasing expression of its downstream targets in endothelial cells, including its receptors (namely, vascular endothelial growth factor receptor‐1 and neuropilin‐1), and FA transport proteins 3 and 4, to suppress endothelial FA uptake, whereas PEDF deletion in mice activated the vascular endothelial growth factor B signaling pathway, thus causing markedly increased lipid accumulation. Conclusions Decreasing expression of PEDF aggravates atherosclerosis by significantly impaired vascular function and enhanced endothelial FA uptake, thus exacerbating ectopic lipid deposition in peripheral tissues.

Background The predictive value of adiposity indices and the newly developed index for cardiometabolic risk factors and cardiovascular diseases (CVDs) remains unclear in the Chinese population. This study aimed to compare the predictive value of A Body Shape Index with other 5 conventional obesity‐related anthropometric indices (body mass index, waist circumference, hip circumference, waist‐to‐hip ratio, waist‐to‐height ratio) in Chinese population. Methods and Results A total of 44 048 participants in the study were derived from the baseline data of the PURE‐China (Prospective Urban and Rural Epidemiology) study in China. All participants’ anthropometric parameters, CVDs, and risk factors (dyslipidemia, abnormal blood pressure, and hyperglycemia) were collected by standard procedures. Multivariable logistic regression models and receiver operator characteristic curve analysis were used to evaluate the predictive values of obesity‐related anthropometric indices to the cardiometabolic risk factors and CVDs. A positive association was observed between each anthropometric index and cardiometabolic risk factors and CVDs in all models (P

Three single reinforcement concrete (RC) frames, including 1 reference specimen and 2 specimens strengthened with shear walls, were fabricated and subjected to low cyclic loadings, in order to evaluate seismic performances of strengthened single frame structures with exterior cantilevers. Through comparison and analysis of failure mode, hysteretic behavior, skeleton curve, energy dissipation, strength, and stiffness degradation of the tested frames, the validity of the shear wall-based reinforcement method for single frames was verified. Test results indicate that the stiffness and load-bearing capacities of strengthened frames increased considerably in comparison with the reference frame. A “strong column-weak beam” failure pattern was observed on the cantilever side, and the failure of the shear wall was always prior to the column, which can increase the structural redundancy and improve the failure mechanism and seismic performance of an existing single frame.

Vehicle aerodynamic shape optimisation is a typical non-linear and computationally expensive black box problem, which is severely limited by time and cost of the objective function evaluations during the global optimisation process. To solve the shortcomings of low efficiency and high cost of the existing vehicle drag reduction method, an improved efficient global optimisation (EGO) algorithm is used to optimise a four-dimensional aerodynamic drag reduction design of a vehicle combined with computational fluid dynamics numerical simulation technology. Moreover, data mining technologies are used to reveal the influence mechanisms of design variables on aerodynamic drag and to analyse the relationship between the variables. It is demonstrated that the improved EGO algorithm, based on the kriging response surface and expected improvement function, can achieve the global optimum with minimum function evaluations. The aerodynamic drag of the optimal design is 1.56% lower than that of the original vehicle. The data mining results showed that the engine hood inclination and the tail upturn angle play a leading role in the vehicle's aerodynamic drag, and the hood inclination has the greatest impact.

Background Triggering receptor expressed on myeloid cells‐1 (TREM‐1) is thought to be critical for inflammatory signal amplification and involved in the development of atherosclerosis. TREM‐1 is significantly increased in patients with myocardial infarction. The aim of this study was to investigate the association between soluble TREM‐1 (sTREM‐1) and mortality and cardiovascular events in patients with acute myocardial infarction. Methods and Results We included 838 consecutive patients with acute myocardial infarction from October 7, 2012 to December 5, 2014. Blood samples were collected from patients with acute myocardial infarction immediately after diagnosis. During follow‐up, 88 patients died, and 180 patients reached the combined end points of major adverse cardiovascular event (MACE). Patients with high sTREM‐1 (higher than the median) had increased risk of all‐cause mortality and MACE compared with those with low sTREM‐1 (log‐rank test, P

BackgroundA considerable amount of studies have examined the relationship between off‐hours (weekends and nights) admission and mortality risk for various diseases, but the results remain equivocal. Methods and ResultsThrough a search of EMBASE, PUBMED, Web of Science, and Cochrane Database of Systematic Reviews, we identified cohort studies that evaluated the association between off‐hour admission and mortality risk for disease. In a random effects meta‐analysis of 140 identified articles (251 cohorts), off‐hour admission was strongly associated with increased mortality for aortic aneurysm (odds ratio, 1.52; 95% CI, 1.30–1.77), breast cancer (1.50, 1.21–1.86), leukemia (1.45, 1.17–1.79), respiratory neoplasm (1.32, 1.20–1.26), pancreatic cancer (1.32, 1.12–1.56), malignant neoplasm of genitourinary organs (1.27, 1.08–1.49), colorectal cancer (1.26, 1.07–1.49), pulmonary embolism (1.20, 1.13–1.28), arrhythmia and cardiac arrest (1.19, 1.09–1.29), and lymphoma (1.19, 1.06–1.34). Weaker (odds ratio

Acute hypotensive episodes (AHEs) are one of the hemodynamic instabilities with high mortality rate that is frequent among many groups of patients. This study presents a methodology to predict AHE for ICU patients based on big data time series. The experimental data we used is mean arterial pressure (MAP), which is transformed from arterial blood pressure (ABP) data. Then, the Hilbert-Huang transform method was used to calculate patient's MAP time series and some features, which are the bandwidth of the amplitude modulation, the frequency modulation, and the power of intrinsic mode function (IMF), were extracted. Finally, the multiple genetic programming (Multi-GP) is used to build the classification models for detection of AHE. The methodology is applied in the datasets of the 10th PhysioNet and Computers Cardiology Challenge in 2009 and Multiparameter Intelligent Monitoring for Intensive Care (MIMIC-II). We achieve the accuracy of 83.33% in the training set and 91.89% in the testing set of the 2009 challenge's dataset and the 84.13% in the training set and 82.41% in the testing set of the MIMIC-II dataset.

Accumulated soluble amyloid beta- (Aβ-) induced aberrant neuronal network activity may directly contribute to cognitive deficits, which are the most outstanding characteristics of Alzheimer’s disease (AD). The entorhinal cortex (EC) is one of the earliest affected brain regions in AD. Impairments of EC neurons are responsible for the cognitive deficits in AD. However, little effort has been made to investigate the effects of soluble Aβ on the discharge properties of EC neurons in vivo. The present study was designed to examine the effects of soluble Aβ1−42 on the discharge properties of EC neurons, using in vivo extracellular single unit recordings. The protective effects of gastrodin (GAS) were also investigated against Aβ1−42-induced alterations in EC neuronal activities. The results showed that the spontaneous discharge of EC neurons was increased by local application of soluble Aβ1−42 and that GAS can effectively reverse Aβ1−42-induced facilitation of spontaneous discharge in a concentration-dependent manner. Moreover, whole-cell patch clamp results indicated that the protective function of GAS on abnormal hyperexcitability may be partially mediated by its inhibitory action on Aβ1−42-elicited inward currents in EC neurons. Our study suggested that GAS may provide neuroprotective effects on Aβ1−42-induced hyperactivity in EC neurons of rats.

We demonstrate that high mobility group box 1 protein (HMGB1) directs Th17 skewing by regulating dendritic cell (DC) function. First, our in vitro studies reveal that recombinant HMGB1 (rHMGB1) activates myeloid DCs to produce IL-23 in vitro, and rHMGB1-activated DCs prime naïve lymphocytes to produce the Th17 cytokine IL-17A. Second, we demonstrate that anti-HMGB1 neutralizing antibody attenuates HMGB1 expression, neutrophilic inflammation, airway hyperresponsiveness, and Th17-related cytokine secretion in vivo by using a murine model of neutrophilic asthma induced by ovalbumin (OVA) plus lipopolysaccharide (LPS). Furthermore, anti-HMGB1 neutralizing antibody decreases the number of Th17 cells in lung cells and suppresses the production of IL-23 by lung CD11C+ APCs. Finally, we show that intranasal adoptive transfer of rHMGB1-activated DCs was sufficient to restore lung neutrophilic inflammation and the Th17 response in a DC-driven model of asthma, whereas the transfer of rHMGB1 plus anti-HMGB1-treated mDCs significantly reduced these inflammation phenotypes. These data suggest, for the first time, that HMGB1 drives the DC-polarized Th17-type response in allergic lung inflammation and that blocking HMGB1 may benefit the attenuation of neutrophilic airway inflammation in asthma.

Clay-brine process employing activated clay, NaCl, HCl, and HF as raw materials is the primarily advanced technology to synthesize cryolite in the present industrial grade. However, plenty of byproducts of fluorine-containing waste HCl at the concentration of about 10%~12% could not be utilized comprehensively and are even hazardous to the environment. This work proposed a new two-step technology to prepare inorganic polymer flocculants polyaluminium chloride (PAC) from synthetic cryolite mother liquor. Many specific factors such as the variety of aluminide source, reaction temperature and time, reagent ratio, and manner of alkaline addition were taken into consideration and their influences on the performances of produced PAC were discussed. It was found that synthetic cryolite mother liquor could react with bauxite and calcium aluminate directly to prepare cheap PAC, with plenty amount of water insoluble CaF2 and CaSiF6 produced as well. However, once HCl was introduced into synthetic cryolite mother liquor as well as by utilizing bauxite as aluminide source and sodium aluminate as adjusting basicity agent, the resultant PAC would dissolve out higher amount of aluminum while producing little amount of water insoluble materials. The coagulation behavior of the specially produced PAC could even match the industrial grade PAC conforming to national standard.