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Abstract Purpose Lung cancer (LC) and breast cancer (BC) are the most common causes of brain metastases (BMs). Time from primary diagnosis to BM (TPDBM) refers to the time interval between initial LC or BC diagnosis and development of BM. This research aims to identify clinical, molecular, and therapeutic risk factors associated with shorter TPDBM. Methods We retrospectively reviewed all diagnosed LC and BC patients with BM at Harbin Medical University Cancer Hospital from 2016 to 2020. A total of 570 patients with LC brain metastasis (LCBM) and 173 patients with breast cancer brain metastasis (BCBM) patients who met the inclusion criteria were enrolled for further analysis. BM free survival time curves were generated using Kaplan–Meier analyses. Univariate and multivariate Cox regression analyses were applied to identify risk factors associated with earlier development of BM in LC and BC, respectively. Results The median TPDBM was 5.3 months in LC and 44.4 months in BC. In multivariate analysis, clinical stage IV and M1 stage were independent risk factors for early development of LCBM. LC patients who received chemotherapy, targeted therapy, pulmonary radiotherapy, and pulmonary surgery had longer TPDBM. For BC patients, age ≥ 50 years, Ki67 ≥ 0.3, HER2 positive or triple‐negative breast cancer subtype, advanced N stage, and no mastectomy were correlated with shorter TPDBM. Conclusions This single‐institutional study helps identify patients who have a high risk of developing BM early. For these patients, early detection and intervention could have clinical benefits.

Abstract Objective To describe a novel method of medial fixation of titanium mesh with a right‐angled screwdriver for orbital floor and maxillary reconstruction and to compare the reconstruction outcome of orbital floor reconstruction with modified and traditional methods. Methods The data of 23 patients who underwent maxillectomy and orbital floor defect reconstruction by individualized titanium mesh in Peking University School and Hospital of Stomatology between 2018 and 2021 were retrospectively reviewed. While eight patients received modified orbital floor reconstruction with titanium mesh and angled screwdriver (group A), 15 patients received traditional orbital floor reconstruction (group B). The contact area with buccal flap for titanium mesh in groups A and B was calculated. Titanium mesh deformation, fracture or exposure was recorded. Postoperative ophthalmic function and success of esthetic restoration were assessed. Results Mean follow‐up was for 15.7 months (range, 9–22 months). The contact area with buccal flap for the modified titanium mesh in group A (13.11 ± 1.41 cm2) was significantly less than that of the traditional titanium mesh in group B (21.83 ± 1.23 cm2; p .05). No specific complications were reported. Conclusion We propose a novel method of zygomatic medial fixation of titanium mesh with a right‐angled screwdriver for orbital floor and maxillary reconstruction, which has the potential to prevent the postoperative exposure of titanium mesh. Level of Evidence Level III (Retrospective comparative study).

Abstract Objective To explore whether MRI‐visible enlarged perivascular spaces (EPVS) are associated with migraine and may serve as a predictor of migraine. Then further explore its correlation with migraine chronification. Methods A total of 231 participants (healthy control [HC] = 57, episodic migraine [EM] = 59, chronic migraine [CM] = 115) were included in this case–control study. A 3T MRI device and the validated visual rating scale were used to assess the grades of EPVS in centrum semiovale (CSO), midbrain (MB), and basal ganglia (BG). Comparisons between the two groups were made using the chi‐square or Fisher's exact tests to initially determine whether high‐grade EPVS were associated with migraine and migraine chronification. A multivariate logistic regression model was constructed to further investigate the role of high‐grade EPVS in migraine. Results The prevalence of high‐grade EPVS in CSO and MB were significantly higher in patients with migraine than in HCs (CSO: 64.94% vs. 42.11%, P = 0.002; MB: 55.75% vs. 29.82%, P = 0.001). Subgroup analysis showed no statistical difference between patients with EM and CM (CSO: 69.94% vs. 62.61%, P = 0.368; MB: 50.85% vs. 58.26%, P = 0.351). Individuals with high‐grade EPVS in CSO (odds ratio [OR]: 2.324; 95% confidence interval [CI]: 1.136–4.754; P = 0.021) and MB (OR: 3.261; 95% CI: 1.534–6.935; P = 0.002) were more likely to suffer from migraine. Interpretation This case–control study showed that high‐grade EPVS in CSO and MB in clinical practice with the underlying mechanism of dysfunction of the glymphatic system could be a predictor of migraine, but no significant correlation had been found with migraine chronification.

Abstract Objective This meta‐analysis aimed to determine the effect of mindfulness interventions on nurses' levels of depression and anxiety. Design Meta‐analysis of randomised controlled trials. Methods The following Chinese and English databases were searched: PubMed, Embase, Cochrane Library, Web of Science, and China National Knowledge Internet (CNKI). The retrieval period was from database construction to 30 March 2022. Two researchers screened the relevant literature and extracted the data. After a cross‐check, data were input into Stata version 16.0 for meta‐analysis. Results Twelve randomised controlled trials from 2017 to 2021 were included, which involved 807 subjects (405 and 402 in the intervention and control groups, respectively). Meta‐analysis results showed that nurses' anxiety reduced by mindfulness‐based interventions was significantly higher compared to that of the control group (SMD = 0.91, 95% CI: 0.27–1.55, p

Abstract Introduction Combined forceps and cryoprobe biopsy during bronchoscopy are increasingly used. However, the adult standard cuffed endotracheal tube (SCETT) is can be limited by general anaesthesia and neuromuscular blockade. An adult uncuffed endotracheal tube (UCETT) might provide simple and safe airway support in stable patients during forceps and cryoprobe biopsy under spontaneous respiration. Methods A retrospective review of stable patients undergoing forceps and cryoprobe biopsy was performed. They were divided into a UCETT group (N = 33) and a SCETT group (N = 27). The primary technical outcome was the successful intubation and completion of bronchoscopy. The primary safety outcome was the incidence of desaturation events. Recovery time and side effects were also recorded. Results UCETTs and SCETTs were successfully inserted, and bronchoscopic procedures were completed in all patients. Only 3/33 (9.1%) patients in the UCETT group exhibited a drop of SPO2

Abstract Fertility is a significant concern among adolescent and young adult (AYA) cancer survivors and their caregivers, especially after their completion of cancer treatment programs. Concerns about fertility affect not only cancer patients' psychological well‐being, but also all aspects of their medical treatments, including treatment protocol, decision‐making, and treatment adherence. In this scoping review, the PubMed, CINAHL, Web of Science, Embase, CNKI, and Wanfang electronic databases were searched according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis Extension for Scoping Reviews. The searches identified 669 articles, 54 of which met the inclusion criteria. Reviewers extracted the data on the study characteristics, measurements, positive factors, negative factors, and additional themes. This scoping review included studies from 10 countries. Most studies were quantitative using a cross‐sectional design. The prevalence of reproductive concerns among AYA cancer survivors ranged from 44% to 86%, and 28% to 44% of the survivors experienced moderate to severe concerns. The specific implementation of fertility consultation, including timing, consult frequency, and content, deserves ongoing exploration.

Phosphoglycerate mutase 1 (PGAM1) is a crucial glycolytic enzyme, and its expression status has been confirmed to be associated with tumor progression and metastasis. However, the precise role and other biological functions of PGAM1 remain unclear. Here, we report that PGAM1 expression is upregulated and related to poor prognosis in patients with breast cancer (BC). Functional experiments showed that knockdown of PGAM1 could suppress the proliferation, invasion, migration, and epithelial–mesenchymal transition of BC cells. Through RNA sequencing, we found that argininosuccinate synthase 1 (ASS1) expression was markedly upregulated in BC cells following PGAM1 knockdown, and it is required to suppress the malignant biological behavior of BC cells. Importantly, we demonstrated that PGAM1 negatively regulates ASS1 expression through the cAMP/AMPK/CEBPB axis. In vivo experiments further validated that PGAM1 promoted tumor growth in BC by altering ASS1 expression. Finally, immunohistochemical analysis showed that downregulated ASS1 levels were associated with PGAM1 expression and poor prognosis in patients with BC. Our study provides new insight into the regulatory mechanism of PGAM1‐mediated BC progression that might shed new light on potential targets and combination therapeutic strategies for BC treatment.

Abstract Background Lung cancer (LC) is one of the most common cancers and a leading cause of cancer‐related deaths worldwide. In many pathological conditions, particularly in the tumor microenvironment, cells and tissues frequently exist in a hypoxic state. Here, we evaluated Itchy E3 ubiquitin protein ligase (ITCH) expression in LC cells following hypoxia treatment. Methods LC cell lines were treated with hypoxic condition. Cell migration, invasion, inflammation, reactive oxygen species (ROS) production, and apoptosis of LC cells were determined by wound healing assay, Transwell invasive assay, ELISA, DCFH‐DA staining, and flow cytometry, respectively. qPCR and WB were used to determine the expression of ITCH and TXNIP. Co‐IP was performed to assess the interaction between ITCH and TXNIP. Results ITCH expression was downregulated in LC cells under hypoxic conditions. Next, LC cells were subjected to hypoxic conditions and changes in cell viability and metastasis were determined. Hypoxic conditions resulted in increased migration and invasion abilities of LC cells. Intracellular reactive oxygen species (ROS) production, inflammation, and apoptosis were also promoted by hypoxia. We found that ITCH overexpression led to the proteasomal degradation of thioredoxin‐interacting protein (TXNIP), whereas the expression of the ITCH C830A mutant did not affect TXNIP levels in LC cells. The gain‐of‐function experiment demonstrated that migration, invasion, ROS generation, inflammation, and apoptosis of hypoxia‐conditioned LC cells were ameliorated by ITCH overexpression, whereas the ITCH C830A mutant did not cause any changes in these phenotypes. Furthermore, the contribution of TXNIP knockdown and ITCH overexpression to the hypoxia‐induced features in LC cells with ITCH C830A was found to be similar. Conclusion Our results suggest a novel mechanism underlying the changes in ITCH‐mediated malignant phenotypes of hypoxia‐conditioned LC cells via TXNIP.

CO2 flooding is recognized as an efficient method for enhancing shale oil recovery, while CO2-oil MMP (minimum miscibility pressure) in the micro-nanoscale is a crucial parameter. This paper presents a method for calculating the MMPs of pure hydrocarbons (C4H10, C6H14, C8H18, and C10H22) and CO2 systems in nanopores (3 nm to 10 nm) with temperature ranging from 290.15 K to 373.15 K. Firstly, we modify the Peng-Robinson equation of state (PR-EOS) by considering the influence of confinement effect and capillary pressure in nanopores. Secondly, the flash calculation algorithm is employed to determine whether the oil and gas phases in nanopores have reached an equilibrium state according to the equality of the fugacity of the two phases. Thirdly, we calculate the interfacial tension (IFT) between the two phases using the Macleod-Sugden equation. When the extrapolated IFT is zero, we treat the corresponding pressure as the MMP of the CO2-oil system in nanopores. Simulation results indicate that the calculated MMP using this method has a relative error of about 0.62% compared to the MMP calculated using the multiple mixing cell (MMC) method, indicating high reliability for MMP prediction. Moreover, the measured MMP at the nanoscale is generally smaller than that in the bulk phase due to the influence of the confinement effect. The MMP is positively correlated with the reservoir temperature, the carbon atom number in alkanes, and the nanopore radius.

Abstract Remarkable exertions are directed to reveal and understand topographic cues that induce cell mechanical sensitive responses including lineage determination. Extracellular matrix (ECM) is the sophisticated ensemble of diverse factors offering the complicated cellular microenvironment to regulate cell behaviors. However, the functions of only a few of these factors are revealed; most of them are still poorly understood. Herein, the focus is on understanding the curved structure in ECM network for regulating stem cell mechanotransduction. A curved nanofiber network mimicking the curved structure in ECM is fabricated by an improved electrospinning technology. Compared with the straight fibers, the curved fibers promote cell bridge formation because of the cytoskeleton tension. The actomyosin filaments are condensed near the curved edge of the non‐adhesive bridge in the bridging cells, which generates higher myosin‐II‐based intracellular force. This force drives cell lineage commitment toward osteogenic differentiation. This study enriches and perfects the knowledge of the effects of topographic cues on cell behaviors and guides the development of novel biomaterials.

Abstract Background Previous studies have demonstrated the preclinical pharmacological and toxicological consistency, and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab (Avastin). This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first‐line treatment of Chinese patients with advanced or recurrent non‐squamous non‐small cell lung cancer (NSCLC). Methods Stage IIIB‐IV NSCLC patients with evaluable lesions, good physical status, and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin (combined treatment) for 4‐6 cycles, followed by maintenance monotherapy with LY01008 until disease progression, intolerable toxicity, or death. The primary endpoint was objective response rate (ORR) in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 confirmed by independent radiological review committees (IRRC). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression‐free survival (PFS), overall survival (OS), and safety. This study was registered in ClinicalTrials.gov (NCT03533127). Results Between December 15th, 2017, and May 15th, 2019, a total of 649 patients were randomized to the LY01008 (n = 324) or Avastin (n = 325) group. As of September 25th, 2019 for primary endpoint analysis, 589 patients received ORR evaluation, with a median number of combined treatment cycles of 5 (range 1‐6) and median duration of treatment of 3.0 (range 0.0‐5.1) months. ORR of response‐evaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%, respectively. The stratified ORR ratio was 0.91 (90% CI 0.80‐1.04, within the prespecified equivalence margin of 0.75‐1.33). Up to May 15th, 2020, with a median follow‐up of 13.6 (range 0.8‐28.4) months, no notable differences in DCR, median DoR, median PFS, median OS, and 1‐year OS rate were observed between the LY01008 and Avastin groups. There were no clinically meaningful differences in safety and immunogenicity across treatment groups. Conclusions LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non‐squamous NSCLC. LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable, metastatic, or recurrent non‐squamous NSCLC patients in the first‐line setting.

Abstract Glioblastoma (GBM) is the most aggressive glioma, and is prone to develop resistance to chemotherapy and radiotherapy; hence, patients with glioblastoma have a high recurrence rate and a low 1‐year survival rate. In addition, the pathogenesis of glioblastoma is complex and largely unknown, and the available treatments are limited. Here, we uncovered a fundamental role of DYRK1A in regulating NFATC1 in GBMs. We found that DYRK1A was highly expressed in glioma and glioblastoma cells, and its expression was positively correlated with that of NFATC1. Moreover, inhibition of DYRK1A promoted NFATC1 degradation in GBM cells and sharply reduced the transactivation of NFATC1, not only by decreasing the expression of NFATC1‐targeted genes, but also by reducing the luciferase activity, and vice versa. However, DYRK1A had the opposite effect on NFATC2. Most importantly, our data suggest that DYRK1A inhibition reduces glioblastoma migration. Polypeptides derived from the DYRK1A‐targeted motif of NFATC1, by competitively blocking DYRK1A kinase activity on NFATC1, clearly destabilized NFATC1 protein and impaired glioblastoma migration. We propose that the recovery of NFATC1 stability is a key oncogenic event in a large proportion of gliomas, and pharmacological inhibition of DYRK1A by polypeptides could represent a promising therapeutic intervention for GBM.

Abstract Lung cancer is the most common cause of cancer‐related deaths. Moreover, exploring efficient tumor‐killing drugs is urgently needed. In our study, several derivative compounds of myricetin were synthesized and tested. Experiments on non‐small cell lung cancer (NSCLC) showed that S4‐2‐2 (5,7‐dimethoxy‐3‐(4‐(methyl(1‐(naphthalen‐2‐ylsulfonyl)piperidin‐4‐yl)amino)butoxy)‐2‐(3,4,5‐trimethoxyphenyl)‐4H‐chromen‐4‐one) had the strongest effect on A549 cell inhibition across all compounds. Furthermore, S4‐2‐2‐treated A549 cells were also suppressed when transplanted into immunodeficient mice. Particularly, we found that the migration and invasiveness of A549 cells became suppressed upon treatment with S4‐2‐2. Furthermore, the compound significantly induced cell apoptosis, but did not affect the cell cycle of A549 cells. Finally, we revealed that S4‐2‐2 inhibited the biological function of NSCLC cells by regulating the protein process in the endoplasmic reticulum, and then by inducing the expression of apoptosis‐related proteins. Taken together, S4‐2‐2 was shown to act as a potential molecular inhibitor of A549 cells.

Given multiple material performance advantages, ceramic matrix composite (CMC) material has become one of the most promising hot structural materials used for thermal protection system in hypersonic vehicles. Under harsh thermal exposure of vehicles in flight, the design of connection structure would be a critical issue in improving load-carrying efficiency and ensuring service safety of aircraft structures in service environments. However, little attention was paid on mechanical behavior and its factors affecting the mechanical property of CMC joining at elevated temperature. To address this concern, a 3D finite element model coupled with progressive damage analysis is carried out to predict high temperature tensile properties and failure behavior of single-lap, double-bolt CMC/superalloy joints assembled by two serial protruding-head bolts. In the implementation of progressive damage analysis of 2D plain-woven C/SiC composites, a user-defined subroutine UMAT including a nonlinear constitutive model, 3D Alvaro failure criterion and Tan’s material degradation rule were embedded into the general package ABAQUS® through Fortran program interface. A parametric study considering geometries of joints was performed to evaluate their resultant influence on high temperature tensile behavior and the associated damage mechanisms for the CMC/superalloy double-bolt joint. New findings were provided for full exploitation of high performance through geometric design of ceramic matrix composite hot structure for hypersonic aircraft.

Abstract Background This study aimed to overexpress or silence connexin 43 (Cx43) and A‐kinase anchoring protein 95 (AKAP95) in human A549 cells to explore their effects on cyclins and on G1/S conversion when the interrelationship of Cx43, AKAP95, and cyclin E1/E2 changes. Methods The study mainly used Western blot analysis and Co‐immuno precipitation to detect the target protein in Cx43/AKAP95 over expressed human A549 cells, and the relationship of proteins Cx43, AKAP95 and Cyclin E during G1‐S phase was explored with qualitative and quantitative analysis. Results The overexpression of Cx43 inhibited the expression of cyclin D1 and E1 by accelerating their degradation and reduced the Cdk2 activity that blocked the DNA transcription activity. However, the overexpression of AKAP95 increased the expression of cyclin D1 and E1 and inhibited their degradation, and enhanced the Cdk2 activity that promoted the DNA transcription activity. Cx43 and AKAP95 competitively bound to cyclin E1/E2, and the competitive binding affected the Cdk2 activity, Rb phosphorylation, DNA transcription activity, and G1/S conversion. Conclusions This study showed that the expression of ERK1/2, PKA, and PKB increased when BEAS‐2B cells were treated with PDGF‐BB, suggesting that ERK1/2, PKA, and PKB might be involved in the binding of AKAP95 with cyclin E, or the separation of AKAP95 from Cx43 from cyclin E1/E2. The specific mechanism underlying this process still needs further exploration.

Abstract Immunoglobulin heavy chain variable region (IGHV) mutational status has been an important prognostic factor for chronic lymphocytic leukemia (CLL) for decades. Patients with unmutated IGHV (≥98% identity to the germline sequence) have inferior prognosis and tend to carry unfavorable genetic markers compared to those with mutated IGHV (

Abstract Na‐O2 batteries are advantageous as the candidates of next‐generation electric vehicles due to their ultrahigh theoretical energy density and have attracted enormous attention recently. Tremendous efforts have been devoted to improve the Na‐O2 battery performance by designing advanced electrodes with various carbon‐based materials. Carbon materials used in Na‐O2 batteries not only function as the air electrode to provide active sites and accommodate discharge products but also as Na anode protectors against dendrite growth and chemical/electrochemical corrosion. In this review, we mainly focus on the application of various carbon‐based materials in Na‐O2 batteries and highlight their advances. The scientific understanding on the fundamental design of the material microstructure and chemistry in relation to the battery performance are summarized. Finally, perspectives on enhancing the overall battery performance based on the optimization and rational design of carbon‐based cell components are also briefly anticipated.

Abstract The development of highly efficient electrocatalysts toward the oxygen evolution reaction is imperative for advancing water splitting technology to generate clean hydrogen energy. Herein, a two dimensional (2D) nanosheet ammonium cobalt phosphate hydrate (NH4CoPO4·H2O) catalyst based on the earth‐abundant non‐noble metal is reported. When used for the challenging alkaline saline water electrolysis, the NH4CoPO4·H2O catalyst with the optimal thickness of 30 nm achieves current densities of 10 and 100 mA cm−2 at the record low overpotentials of 252 and 268 mV, respectively, while maintaining remarkable stability during the alkaline saline water oxidation at room temperature. X‐ray absorption fine spectra reveal that the activation of Co (II) ions (in NH4CoPO4·H2O) to Co (III) species constructs the electrocatalytic active sites. The 2D nanosheet morphology of NH4CoPO4·H2O provides a larger active surface area and more surface‐exposed active sites, which enable the nanosheet catalyst to facilitate the alkaline freshwater and simulated seawater oxidation with excellent activity. The facile and environmentally‐benign H2O‐mediated synthesis route under mild condition makes NH4CoPO4·H2O catalyst highly feasible for practical manufacturing. In comparison with noble metals, this novel electrocatalyst offers a cost‐effective alternative for economic saline water oxidation to advance water electrolysis technology.

Abstract Red blood cell distribution width (RDW), which measures the range of variation of red blood cell volume, has been explored as a prognostic factor in multiple types of cancer. However, the role of RDW in mantle cell lymphoma (MCL), a rare type of non‐Hodgkin lymphoma with poor outcomes, remains to be determined. Therefore, we investigated the prognostic role of RDW in MCL. We found that 21 of 76 MCL patients (27.6%) had an abnormally elevated RDW (>15.7%). Abnormally elevated RDW was significantly associated with presence of B symptoms (P = 0.0020), elevated lactate dehydrogenase (LDH) (P = 0.0010), higher leukocyte count (P = 0.0345), higher simplified Mantle Cell International Prognostic Index (sMIPI) (P = 0.0194), and lower level of hemoglobin (Hb) (P 15.8%) predicted shorter progression‐free survival (PFS) (hazards ratio [HR]: 3.14; P = 0.0005) and shorter overall survival (OS) (HR: 4.04; P

The introduction of customized bus (CB) service intends to expand and elevate existing transit service, which offers an efficient and sustainable alternative to serve commuters. A probabilistic model is proposed to optimize CB service with mixed vehicle sizes in an urban setting considering stochastic bus arrival time and spatiotemporal demand, which minimizes total cost subject to bus capacity and time window constraints. The studied optimization problem is combinatorial with many decision variables including vehicle assignment, bus routes, timetables, and fleet size. A heuristic algorithm is developed, which integrates a hybrid genetic algorithm (HGA) and adaptive destroy-and-repair (ADAR) method. The efficiency of HGA-ADAR is demonstrated through numerical comparisons to the solutions obtained by LINGO and HGA. Numerical instances are carried out, and the results suggested that the probabilistic model considering stochastic bus arrival time is valuable and can dramatically reduce the total cost and early and late arrival penalties. A case study is conducted in which the proposed model is applied to optimize a real-world CB service in Xi’an, China. The relationship between decision variables and model parameters is explored. The impacts of time window and variance of bus arrival time, which significantly affect service reliability, are analysed.

For the large-scale search and rescue (S&R) scenarios, the centralized and distributed multi-UAV multitask assignment algorithms for multi-UAV systems have the problems of heavy computational load and massive communication burden, which make it hard to guarantee the effectiveness and convergence speed of their task assignment results. To address this issue, this paper proposes a hierarchical task assignment strategy. Firstly, a model decoupling algorithm based on density clustering and negotiation mechanism is raised to decompose the large-scale task assignment problem into several nonintersection and complete small-scale task assignment problems, which effectively reduces the required computational amount and communication cost. Then, a cluster head selection method based on multiattribute decision is put forward to select the cluster head for each UAV team. These cluster heads will communicate with the central control station about the latest assignment information to guarantee the completion of S&R mission. At last, considering that a few targets cannot be effectively allocated due to UAVs’ limited and unbalanced resources, an auction-based task sharing scheme among UAV teams is presented to guarantee the mission coverage of the multi-UAV system. Simulation results and analyses comprehensively verify the feasibility and effectiveness of the proposed hierarchical task assignment strategy in large-scale S&R scenarios with dispersed clustering targets.

Objective. To determine the role of sodium butyrate in intestinal inflammation via regulation of high-mobility group box-1 (HMGB1), we analyzed the potential mechanism in necrotizing enterocolitis (NEC) in a neonatal mouse model. Methods. A NEC model was created with hypoxia and cold exposure and artificial overfeeding. C57BL/6 neonatal mice were randomized into three groups: the control, untreated NEC, and sodium butyrate (150 mM)-pretreated NEC groups. Pathological variations in ileocecal intestinal tissue were observed by HE staining and scored in a double-blind manner. The mRNA expression levels of HMGB1, Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB), and inflammatory cytokines in intestinal tissues were determined by quantitative real-time PCR. The protein levels of HMGB1 and associated cytokines in intestinal tissues were evaluated using ELISA. The relative protein expression levels of TLR4 and NF-κB in intestinal tissues were quantified by western blot. Results. Sodium butyrate administration improved the body weight and survival rate of NEC mice; relieved intestinal pathological injury; reduced the intestinal expression of HMGB1, TLR4, NF-κB, interleukin- (IL-) 1β, IL-6, IL-8, and TNF-α; and increased the intestinal expression of IL-10 (P

There are a large number of photovoltaic (PV) arrays in large-scale PV power plants or regional distributed PV power plants, and the output of different arrays fluctuates with the external conditions. The deviation and evolution information of the array output are easily covered by the random fluctuations of the PV output, which makes the fault diagnosis of PV arrays difficult. In this paper, a fault diagnosis method based on the deviation characteristics of the PV array output is proposed. Based on the current of the PV array on the DC (direct current) side, the deviation characteristics of the PV array output under different arrays and time series are analyzed. Then, the deviation function is constructed to evaluate the output deviation of the PV array. Finally, the fault diagnosis of a PV array is realized by using the probabilistic neural network (PNN), and the effectiveness of the proposed method is verified. The main contributions of this paper are to propose the deviation function that can extract the fault characteristics of PV array and the fault diagnosis method just using the array current which can be easily applied in the PV plant.

Multitasking evolutionary algorithm (MTEA), which solves multiple optimization tasks simultaneously in a single run, has received considerable attention in the community of evolutionary computation, and several algorithms have been proposed in the literature. Unfortunately, knowledge transfer between constituent tasks may cause negative effect on algorithm performance, especially when the optimal solutions of all tasks are in different locations of the unified search space. To address this issue, an effective variable transformation strategy and the corresponding inverse transformation are proposed in multitasking optimization scenario. After using variable transformation strategy, the estimated optimal solutions of all tasks are both near the center point of the unified search space. More importantly, this strategy can enhance the task similarity, and then the effectiveness of knowledge transfer will probably be positive in this case, which can help us to improve the algorithm performance. Keeping this in mind, a multitasking evolutionary algorithm (named MTDE-VT) is realized as an instance by embedding the proposed variable transformation strategy into multitasking differential evolution. In MTDE-VT, the individuals in the original population are first transformed into new locations by the variable transformation strategy. Once the offspring is generated in the transformed unified search space, it must be transformed back to the original unified search space. The statistical analysis of experimental results on some multitasking optimization benchmark problems illustrates the superiority of the proposed MTDE-VT algorithm in terms of solution accuracy and robustness. Furthermore, the basic principle and the good parameter combination are also provided based on massive simulated data.

Recently, it was demonstrated that multitasking evolutionary algorithm (MTEA), a newly proposed algorithm, can solve multiple optimization problems simultaneously through a single run, breaking through the limitations of traditional evolutionary algorithms (EAs), with good convergence and exploration performance. As a novel algorithm, MTEA still has a lot of unexplored space. Generally speaking, the order of solution variables has no significant influence on the single-tasking EAs. To our knowledge, the effect of the order of variables in the multitasking scenario has not been explored. To fill in this research gap, three orders of variables in the multitasking scenario are proposed in this paper, including full reverse order, bisection reverse order, and trisection reverse order. An important feature of these orders of variables is that an individual can recover as himself after two times of changing the order of variables. In order to verify our idea, these orders of variables are embedded into MTEA. The experiment results revealed that the effect of the different orders of variables is universal but not significant enough in the practical application. Furthermore, tasks with high similarity and high degree of intersection are sensitive to the order of variables and get great impact between tasks.

Abstract Because of the exclusion for the patients more than 75 years (very elderly patients) in many clinical trials of esophageal cancer (EC), there is no consensus on prognosis and treatment for this population. We aim to evaluate the outcomes and aging‐related prognostic factors of definitive radiotherapy (RT) for very elderly EC patients. We retrospectively analyzed 149 very elderly EC patients consecutively treated between January 2015 and June 2016 by definitive intensity‐modulated radiotherapy (IMRT) with or without chemotherapy. The clinical outcome and toxicities were assessed, and the potential prognostic factors, such as nutritional risk index (NRI) and neutrophil–lymphocyte ratio (NLR), were analyzed statistically. The median follow‐up time for survivors was 22.5 months. The 2‐year overall survival (OS), local–regional failure‐free survival (LRFFS), and distant metastasis‐free survival (DMFS) were 51.6%, 54.7%, and 85.2%, respectively. Independent predictors for poorer OS were higher American Joint Committee on Cancer (AJCC) stage, lower NRI, and higher NLR value before RT. Meanwhile, the total dose (cutoff value 60 Gy) of planning gross tumor volume (PGTV) and chemotherapy was also identified as independent prognostic indicator for LRFFS and DMFS, respectively. 72 patients had treatment failure and 58 (80.6%), 6 (8.3%), and 18 (25.0%) patients had experienced local, regional, and distant failure, respectively. Few severe toxicities were observed. The conservative definitive RT with modern technique was effective for very elderly EC patients in short term with low rate and tolerable toxicities. Local residue or recurrence was the most common failure pattern. The aging‐related prognostic factors concerned nutrition and immune, such as NRI and NLR before RT, should be considered for use in future clinical practice.

Workforce planning is an operation management problem in the delivery industry to improve service quality and reliability, and the working attitude and passion of drivers, as the direct implementors of delivery service, affect the service level. Consequently, assigning equal workload for drivers so as to improve drivers’ acceptance is a reasonable and efficient workforce plan for managers. This paper investigates a periodic driver routing problem to explore the relationship between workload differential among drivers and total workload; the objective of the optimization problem is to minimize the total workload. To tackle this problem, we first propose a mixed-integer linear programming model, which can be solved by an off-the-shelf mixed-integer linear programming solver, and use the local branching based method to solve larger instances of the problem. Numerical experiments are conducted to validate the effectiveness and efficiency of the proposed model and solution method, as well as the effect of small workload differential among drivers on the total workload.

The voltage violation phenomenon can be very prominent in the condition of dispersed wind power (DWP) widely integrated into network, which affects the safe operation during integration and effective consumption of wind power. In this study, a self-discipline control strategy of DWP is proposed to solve the voltage violation problem with high penetration. First, the influence of system voltage after the DWP integrated into network is analysed, which raises the feasibility of self-discipline control strategy. Then, according to the proposed strategy, the object of optimisation model is designed to better the voltage quality of the grid connection point of wind power generator and to maximise the active power outputs of wind power. Considering the non-linear and multivariable characteristics of the optimisation model, this study used the particle swarm optimisation to obtain the reactive power and active power regulations of wind power. Finally, the proposed algorithm is tested and analysed on the IEEE 33-node distribution system, and verified by a practical project. The results show that the self-discipline control strategy can effectively eliminate the voltage violation caused by the DWP integration. Moreover, the wind power can be fully utilised.

Background. HTRA2 has already been nominated as PARK13 which may cause Parkinson’s disease, though there are still discrepancies among these results. Recently, Gulsuner et al.’s study found that HTRA2 p.G399S is responsible for hereditary essential tremor and homozygotes of this allele develop Parkinson’s disease by examining a six-generation family segregating essential tremor and essential tremor coexisting with Parkinson’s disease. We performed this study to validate the condition of HTRA2 gene in Chinese familial essential tremor and familial Parkinson’s disease patients, especially essential tremor. Methods. We directly sequenced all eight exons, exon-intron boundaries, and part of the introns in 101 familial essential tremor patients, 105 familial Parkinson’s disease patients, and 100 healthy controls. Results. No exonic variant was identified, while one exon-intron boundary variant (rs2241028) and one intron variant (rs2241027) were detected, both with no clinical significance and uncertain function. There was no difference in allele, genotype, and haplotype between groups. Conclusions. HTRA2 exonic variant might be rare among Chinese Parkinson’s disease and essential tremor patients with family history, and HTRA2 may not be the cause of familial Parkinson’s disease and essential tremor in China.

Vibration signals extracted from rotating parts of machinery carry a lot of useful information about the condition of operating machine. Due to the strong non-linear, complex and non-stationary characteristics of vibration signals from working bearings, an accurate and reliable health assessment method for bearing is necessary. This paper proposes to utilize the selected chaotic characteristics of vibration signal for health assessment of a bearing by using self-organizing map (SOM). Both Grassberger-Procaccia algorithm and Takens' theory are employed to calculate the characteristic vector which includes three chaotic characteristics, such as correlation dimension, largest Lyapunov exponent and Kolmogorov entropy. After that, SOM is used to map the three corresponding characteristics into a confidence value (CV) which represents the health state of the bearing. Finally, a case study based on vibration datasets of a group of testing bearings was conducted to demonstrate that the proposed method can reliably assess the health state of bearing.

Glutamate is an important excitatory neurotransmitter in mammalian brains, but excessive amount of glutamate can cause “excitotoxicity” and lead to neuronal death. As bipolar neurons, spiral ganglion neurons (SGNs) function as a “bridge” in transmitting auditory information from the ear to the brain and can be damaged by excessive glutamate which results in sensorineural hearing loss. In this study, edaravone, a free radical scavenger, elicited both preventative and therapeutic effects on SGNs against glutamate-induced cell damage that was tested by MTT assay and trypan blue staining. Ho.33342 and PI double staining revealed that apoptosis as well as necrosis took place during glutamate treatment, and apoptosis was the main type of cell death. Oxidative stress played an important role in glutamate-induced cell damage but pretreatment with edaravone alleviated cell death. Results of western blot demonstrated that mechanisms underlying the toxicity of glutamate and the protection of edaravone were related to the PI3K pathway and Bcl-2 protein family.

Recent research confirms that slip of a fluid on the solid surface occurs at micrometer scale. Slip on solid surface may cause the change of interior material deformation which consequently leads to the change of velocity profile and stress field. This paper concerns the time periodic electroosmotic flow in a channel with slip boundary driven by an alternating electric field, which arises from the study of particle manipulation and separation such as flow pumping and mixing enhancement. Although exact solutions to various flow problems of electroosmotic flows under the no-slip condition have been obtained, exact solutions for problems under slip boundary conditions have seldom been addressed. In this paper, an exact solution is derived for the time periodic electroosmotic flow in two-dimensional straight channels under slip boundary conditions.

This paper is concerned with the existence and nonexistence of positive solutions for a nonlinear higher-order three-point boundary value problem. The existence results are obtained by applying a fixed point theorem of cone expansion and compression of functional type due to Avery, Henderson, and O’Regan.

We study the slip flow of fluids driven by the combined effect of electrical force and pressure gradient. The underlying boundary value problem is solved through the use of Fourier series expansion in time and Bessel function in space. The exact solutions and numerical investigations show that the slip length and electrical field parameters have significant effects on the velocity profile. By varying these system parameters, one can achieve smooth velocity profiles or wave form profiles with different wave amplitude and frequency. This opens the way for optimizing the flow by choosing the slip length, the electrical field, and electrolyte solutions.