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Abstract The central nervous system (CNS) is the most delicate system in human body, with the most complex structure and function. It is vulnerable to trauma, infection, neurodegeneration and autoimmune diseases, and activates the immune system. An appropriate inflammatory response contributes to defence against invading microbes, whereas an excessive inflammatory response can aggravate tissue damage. The NLRP3 inflammasome was the first one studied in the brain. Once primed and activated, it completes the assembly of inflammasome (sensor NLRP3, adaptor ASC, and effector caspase-1), leading to caspase-1 activation and increased release of downstream inflammatory cytokines, as well as to pyroptosis. Cumulative studies have confirmed that NLRP3 plays an important role in regulating innate immunity and autoimmune diseases, and its inhibitors have shown good efficacy in animal models of various inflammatory diseases. In this review, we will briefly discuss the biological characteristics of NLRP3 inflammasome, summarize the recent advances and clinical impact of the NLRP3 inflammasome in infectious, inflammatory, immune, degenerative, genetic, and vascular diseases of CNS, and discuss the potential and challenges of NLRP3 as a therapeutic target for CNS diseases.

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Introduction The Shenzhen government is widely considered to be most efficiently implementing smoke-free legislation in China. We evaluated and compared the impact of Shenzhen’s two-phase smoke-free regulation on the incidence rates for ischemic and hemorrhagic stroke. Methods An interrupted time series design was used to capture immediate and annual incidence changes from 2007 to 2016 for both ischemic and hemorrhagic stroke due to two-phase smoke-free regulation in Shenzhen, China, by using a generalized additive model. The first phase, implemented on 9 March 2010, required five main public places to be smoke-free. In the second phase, the comprehensive law was expanded to the whole city on 1 March 2014. Results The regulation implementation during phase I was associated with a strong immediate decline in the incidence rate of ischemic stroke (-14.2%, 95% CI: -19.6 – -8.4) and hemorrhagic stroke (-10.1%, 95% CI: -18.2 – -1.2), but without showing the annual changes (p>0.05). Following the implementation of the comprehensive law, the gradual annual effect showed a significant change in ischemic stroke, with a 6.3% (95% CI: 8.9 – -3.6) reduction. Neither the immediate nor gradual decreases in hemorrhagic stroke incidences associated with the comprehensive regulation were statistically significant during phase II (p>0.05). Subgroup analyses indicate that a much larger health effect of the regulation during phase I was greater among those aged ≥65 years than among those aged 35–64 years. Conclusions Shenzhen’s two-phase smoke-free regulation was well implemented. Even though the regulation did not extend to the whole city, the immediate health benefits on the incidence rates of ischemic stroke and hemorrhagic stroke could be seen. However, the health benefits brought by the implementation of comprehensive smoke-free legislation were attenuated by previous smoke-free regulations in five main public places, which were more evident in hemorrhagic stroke.

The precise tie-points (TPs) on synthetic aperture radar (SAR) images are a critical cornerstone in the global digital elevation model (DEM) and digital ortho map (DOM) production process. While there are abundant studies on SAR TPs matching, improvement opportunities persist in large areas. The correspondences have pixel-level errors during geocoding, which result in misalignment between global products. Consequently, this paper proposed a robust method for SAR images TPs matching, which consists of three key steps: (1) interest point extraction based on the dynamic Harris area entropy (DHAE) grid; (2) adaptive determination of template size; (3) normalized cross correlation (NCC) template matching. DHAE is a regional texture information grid based on the SAR-Harris map, and it is achieved through dynamic block division. Generating the DHAE grid over SAR images enables the extraction of interest points that have regional feature representation and distribution uniformity. A variable-size matching template is adaptively determined based on DHAE to enhance template quality while maintaining computational efficiency. Subsequently, the NCC algorithm is employed to find subpixel-precise correspondences. The proposed method is applied on TPs matching in 57 Terra-SAR images, which cover a large geographical area. Furthermore, the overlapping area is partitioned into five segments according to different coverage types. The experimental results demonstrate that the proposed method outperforms other template matching methods. For all coverage types, the proposed method exhibits high-precision sub-pixel results that reach up to 38.64% in terms of the relative positioning error (RPE), particularly in texture-weak and large areas.

Abstract Objectives To statistically study the 3D shape of oesophageal cancer (EC) and its spatial relationships based on computed tomography angiography (CTA) 3D reconstruction, to determine its relationship with T‐stages, and to create an optimal T‐stage diagnosis protocol based on CTA calculation. Methods Pre‐operative CTA images of 155 patients with EC were retrospectively collected and divided into four groups: T1–T4. We used Amira software to segment and 3D reconstruct the EC, oesophagus, aorta, pericardium and peripheral lymph nodes and measured their surface area, volume, major axis, minor axis, longitudinal length, roughness and relationship to the aorta of the EC. One‐way ANOVA, independent sample t‐test, ROC, etc., were performed and critical values between different T‐stages were calculated. We also invited two radiologists to evaluate the measurements. Results There were no significant differences in EC longitudinal length, roughness score and relationship with the aorta between the different T‐stages of EC. There were significant differences in EC surface area, EC volume and mean major and minor axis among the different T‐stages. The volumes of the T1–T4 tumours were 12,934.36 ± 7739.25, 23,095.27 ± 14,975.67, 37,577.98 ± 36,085.64 and 58,579.25 ± 41,073.96 mm3 separately (p

Abstract Background Triple‐negative breast cancer (TNBC) is the most aggressive type of breast cancer. Immune checkpoint inhibitors (ICIs) have been widely used to treat various tumors and have changed the landscape of tumor management, but the data from real‐world studies of ICIs for TNBC treatment remain limited. The aim of this study was to evaluate the efficacy of ICIs in the treatment of patients with advanced TNBC in a real‐world setting and to explore possible correlates. Methods The clinical data of advanced TNBC patients who received ICI treatment in the Chinese People's Liberation Army (PLA) General Hospital were collected. Treatment responses, outcomes and adverse events (AEs) were assessed. Results Eighty‐one patients were included in the study. The confirmed objective response rate (ORR) was 32.1%, and the disease control rate (DCR) was 64.2%. The median progression‐free survival (PFS) was 4.2 months, and the median overall survival (OS) was 11.0 months. PFS and OS were longer in patients who achieved clinical benefit from ICIs and shorter in patients who received later‐line ICIs and higher levels of inflammation; specifically, patients with higher TILs had longer PFS. Overall AEs were tolerable. Conclusions ICIs are effective in the treatment of advanced TNBC, and the adverse reactions are tolerable. A panel of biomarkers including LDH, ALP, and bNLR were identified to predict the efficacies of ICIs in TNBC treatment.

AbstractIn the face of increasing global unsustainable risks such as poverty, hunger, and pollution. Building sustainable agriculture (SA) in the digital age is a fundamental task for human survival. Based on the coupled coordination perspective, this paper constructs an SA system that takes into account more stakeholders by considering poverty alleviation and income increase (PI), food security (FS), and green agriculture (GA) as subsystems. The impact of digital technology on SA is systematically analyzed through data from 276 prefecture-level and above cities in China from 2005 to 2020. The study shows that digital technology has a significant upgrading effect on SA and its subsystems. And digital technology is more likely to promote SA in the developed eastern region and peripheral cities. Moreover, agricultural productivity and labor productivity play a mediating mechanism in the process of digital technology for SA. Digital financial inclusion fuels the high input process of digital technology for incentivizing SA, PI, and GA, but it cannot affect the highly technical process of digital farming. Further research found that the incentives of digital technology for SA and GA are characterized by the nonlinear characteristic of increasing marginal effects. Due to the second digital divide, there is a U-shaped incentive process of digital technology for PI to fall and then rise. Finally, the spillover nature of digital technology leads to spatial spillovers in its contribution to SA development.

Abstract Background Macro-autophagy/Autophagy is an evolutionarily well-conserved recycling process to maintain the balance through precise spatiotemporal regulation. However, the regulatory mechanisms of biomolecular condensates by the key adaptor protein p62 via liquid-liquid phase separation (LLPS) remain obscure. Results In this study, we showed that E3 ligase Smurf1 enhanced Nrf2 activation and promoted autophagy by increasing p62 phase separation capability. Specifically, the Smurf1/p62 interaction improved the formation and material exchange of liquid droplets compared with p62 single puncta. Additionally, Smurf1 promoted the competitive binding of p62 with Keap1 to increase Nrf2 nuclear translocation in p62 Ser349 phosphorylation-dependent manner. Mechanistically, overexpressed Smurf1 increased the activation of mTORC1 (mechanistic target of rapamycin complex 1), in turn leading to p62 Ser349 phosphorylation. Nrf2 activation increased the mRNA levels of Smurf1, p62, and NBR1, further promoting the droplet liquidity to enhance oxidative stress response. Importantly, we showed that Smurf1 maintained cellular homeostasis by promoting cargo degradation through the p62/LC3 autophagic pathway. Conclusions These findings revealed the complex interconnected role among Smurf1, p62/Nrf2/NBR1, and p62/LC3 axis in determining Nrf2 activation and subsequent clearance of condensates through LLPS mechanism.

Accurate and complete digital elevation models (DEMs) play an important fundamental role in geospatial analysis, supporting various engineering applications, human activities, and scientific research. Interferometric synthetic aperture radar (InSAR) plays an increasingly important role in DEM generation. Nonetheless, owing to its inherent characteristics, gaps often appear in regions marked by significant topographical fluctuations, necessitating an extra void-filling process. Traditional void-filling methods have operated directly on preexisting data, succeeding in relatively flat terrain. When facing mountainous regions, there will always be gross errors in elevation values. Regrettably, conventional methods have often disregarded this vital consideration. To this end, this research proposes a DEM void-filling method based on incorporating elevation outlier detection. It accounts for the detection and removal of elevation outliers, thereby mitigating the shortcomings of existing methods and ensuring robust DEM restoration in mountainous terrains. Experiments were conducted to validate the method applicability using TanDEM-X data from Sichuan, China, Hebei, China, and Oregon, America. The results underscore the superiority of the proposed method. Three traditional methods are selected for comparison. The proposed method has different degrees of improvement in filling accuracy, depending on the void status of the local terrain. Compared with the delta surface fill (DSF) method, the root mean squared error (RMSE) of the filling results has improved by 7.87% to 51.87%. The qualitative and quantitative experiments demonstrate that the proposed method is promising for large-scale DEM void-filling tasks.

In order to prepare polyimide (PI) films with a low dielectric constant and excellent comprehensive performance, a two-step method was employed in this study to integrate β-cyclodextrin into a semi-aromatic fluorine-containing polyimide ternary system. By introducing trifluoromethyl groups to reduce the dielectric constant, the dielectric constant was further reduced to 2.55 at 10 MHz. Simultaneously, the film exhibited noteworthy thermal stability (a glass transition temperature exceeding 300 °C) and a high coefficient of thermal expansion. The material also demonstrated outstanding mechanical properties, boasting a strength of 122 MPa and a modulus of 2.2 GPa, along with high optical transparency (transmittance reaching up to 89% at 450 nm). Moreover, the inherent high transparency of colorless polyimide (CPI) combined with good stretchability contributed to the attainment of a low dielectric constant. This strategic approach not only opens up new opportunities for novel electroactive polymers but also holds potential applications in flexible displays, circuit printing, and chip packaging.

Accurate short-term wind power prediction is of great significance to the real-time dispatching of power systems and the development of wind power generation plans. However, existing methods for wind power prediction have the following problems: 1) some studies aim at predicting wind power for a single wind farm, ignoring the correlations of the adjacent wind farms; 2) many studies tend to convert wind speed forecast results to wind power, increasing the conversion error; 3) almost all studies place emphasis on the capture of spatiotemporal features, neglecting the influence of spatiotemporal coupling. Therefore, to solve the above questions, this work proposes an adaptive graph neural network based on spatiotemporal attention calculation for short-term wind farm cluster power prediction, using only wind power data. Firstly, a dynamic undirected graph is established to sufficiently learn prior knowledge of spatial relationships. Next, the spatiotemporal coupling relationship and global temporal correlation between data can be computed by performing spatiotemporal cross-attention and temporal self-attention, respectively. Finally, a novel hybrid loss function is proposed to optimize the prediction model accurately. In a case study, compared with other benchmark methods, the proposed method shows excellent overall performance in predicting wind power.

Abstract Background Both vasovagal syncope (VVS) and epilepsy present with transient loss of consciousness and are often difficult to identify. Hence this study aimed to explore the value of QT interval in the differentiation of VVS and epilepsy in children. Methods One hundred thirteen children with unexplained transient loss of consciousness were selected. 56 children with VVS (VVS group), including 37 males and 19 females, the average age is 9.88 ± 2.55 years old. 57 children with epilepsy (epilepsy group), including 36 males and 21 females, the average age is 8.96 ± 2.67 years old. At the same time, the 60 healthy individuals (control group) were examined according to age and sex. The QT interval of 12-lead electrocardiogram in a basal state of three groups was measured and statistically analyzed by SPSS 24.0 software. Results Compared with the control group, (1) QTcmax, QTcmin and QTcd were significantly longer in VVS group (P 0.05). (2) The QTmax and QTmin were significantly shorter in epilepsy group (P 0.05). Compared with the epilepsy group, The QTcmax, QTcmin, QTcd were significantly longer in VVS group (P 0.05). When QTcmax > 479.84 ms, QTcmin > 398.90 ms and QTcd > 53.56 ms, the sensitivity and specificity of diagnosing VVS were 62.5% and 77.19%, 82.14% and 50.88%, 82.14% and 38.60% respectively. Conclusion QTcmax, QTcmin and QTcd have certain value in differentiating VVS from epilepsy in children.

Heterogeneous image features are complementary, and feature fusion of heterogeneous images can increase position effectiveness of occluded apple targets. A YOLOfuse apple detection model based on RGB-D heterogeneous image feature fusion is proposed. Combining the CSPDarknet53-Tiny network on the basis of a YOLOv5s backbone network, a two-branch feature extraction network is formed for the extraction task of RGB-D heterogeneous images. The two-branch backbone network is fused to maximize the retention of useful features and reduce the computational effort. A coordinate attention (CA) module is embedded into the backbone network. The Soft-NMS algorithm is introduced, instead of the general NMS algorithm, to reduce the false suppression phenomenon of the algorithm on dense objects and reduce the missed position rate of obscured apples. It indicates that the YOLOfuse model has an AP value of 94.2% and a detection frame rate of 51.761 FPS. Comparing with the YOLOv5 s, m, l, and x4 versions as well as the YOLOv3, YOLOv4, YOLOv4-Tiny, and Faster RCNN on the test set, the results show that the AP value of the proposed model is 0.8, 2.4, 2.5, 2.3, and 2.2 percentage points higher than that of YOLOv5s, YOLOv3, YOLOv4, YOLOv4-Tiny, and Faster RCNN, respectively. Compared with YOLOv5m, YOLOv5l, and YOLOv5x, the speedups of 9.934FPS, 18.45FPS, and 23.159FPS are obtained in the detection frame rate, respectively, and the model are better in both of parameter’s number and model size. The YOLOfuse model can effectively fuse RGB-D heterogeneous source image features to efficiently identify apple objects in a natural orchard environment and provide technical support for the vision system of picking robots.

Systemic lupus erythematosus (SLE) is an autoimmune disease with multi-system involvement as the main manifestation, and has complex and diverse clinical features. Studies on large samples have revealed that SLE patients have a significantly increased risk of thrombotic events, which are also one of the important causes of morbidity and mortality in SLE patients. Antiphospholipid syndrome (APS) is a rare autoimmune disorder characterized by recurrent arterial and venous thrombosis, pregnancy-related complications, and the persistence of antiphospholipid antibodies at a 12-week interval. There are few reports about SLE coexisting with APS in children. This paper reported a school-age patient who started the disease with gross hematuria after bumping into the waist. The initial diagnosis of renal contusion was then confirmed by color Doppler ultrasound as renal vein and inferior vena cava embolism. She suddenly developed severe chest pain and dyspnea 3 days after hospitalization. And imaging supported pulmonary embolism with massive proteinuria, hypoalbuminemia, and hypercholesterolemia. The initial diagnosis was nephrotic syndrome (NS) with arteriovenous embolization, and popliteal vein embolism occurred again 5 years later, and she was thus diagnosed with SLE coexisting with APS. Afterwards, we discussed the possible mechanism and therapeutic strategies of SLE&APS that started with nephrotic syndrome, in order to achieve early identification and treatment of the disease and improve the prognosis of children.

Abstract Background Social media has become an essential tool to implement risk communication, giving health information could gain more exposure by retweeting during the COVID-19 pandemic. Methods Content analysis was conducted to scrutinize the official (national and provincial) public health agencies’ Weibo posts (n = 4396) to identify features of information sources and message features (structure, style content). The Zero-Inflated Negative Binomial (ZINB) model was adopted to analyze the association between these features and the frequency of the retweeted messages. Results Results indicated that features of source and health information, such as structure, style, and content, were correlated to retweeting. The results of IRR further suggested that compared to provincial accounts, messages from national health authorities’ accounts gained more retweeting. Regarding the information features, messages with hashtags#, picture, video have been retweeted more often than messages without any of these features respectively, while messages with hyperlinks received fewer retweets than messages without hyperlinks. In terms of the information structure, messages with the sentiment (!) have been retweeted more frequently than messages without sentiment. Concerning content, messages containing severity, reassurance, efficacy, and action frame have been retweeted with higher frequency, while messages with uncertainty frames have been retweeted less often. Conclusions Health organizations and medical professionals should pay close attention to the features of health information sources, structures, style, and content to satisfy the public’s information needs and preferences to promote the public's health engagement. Designing suitable information systems and promoting health communication strategies during different pandemic stages may improve public awareness of the COVID-19, alleviate negative emotions, and promote preventive measures to curb the spread of the virus.

AimsEpilepsy is a neurological disease occurring worldwide. Alterations in the gut microbial composition may be involved in the development of Epilepsy. The study aimed to investigate the effects of cannabidiol (CBD) on gut microbiota and the metabolic profile of epileptic rats.Materials and methods and resultsA temporal lobe epilepsy rat model was established using Li-pilocarpine. CBD increased the incubation period and reduced the epileptic state in rats. Compared to epileptic rats, the M1/M2 ratio of microglia in the CBD group was significantly decreased. The expression of IL-1β, IL-6, and TNF-α in the CBD group decreased, while IL-10, IL-4, and TGF-β1 increased. 16S rDNA sequencing revealed that the ANOSIM index differed significantly between the groups. At the genus level, Helicobacter, Prevotellaceae_UCG-001, and Ruminococcaceae_UCG-005 were significantly reduced in the model group. CBD intervention attenuated the intervention effects of Li-pilocarpine. Roseburia, Eubacterium_xylanophilum_group, and Ruminococcus_2 were strongly positively correlated with proinflammatory cytokine levels. CBD reversed dysregulated metabolites, including glycerophosphocholine and 4-ethylbenzoic acid.ConclusionCBD could alleviate the dysbiosis of gut microbiota and metabolic disorders of epileptic rats. CBD attenuated Epilepsy in rats might be related to gut microbial abundance and metabolite levels.Significance and impact of studyThe study may provide a reliable scientific clue to explore the regulatory pathway of CBD in alleviating Epilepsy.

This paper analyzes an agency model of crisis bargaining where two states have private information about war payoffs. In the model, two leaders bargain on behalf of their own states. Importantly, owing to political bias and audience costs, a leader’s war payoff and peace payoff differ from those of her state at large. I establish general results about leaders’ bargaining strategies and the possibility of peaceful resolution. By examining incentive compatibility constraints, I show that in any equilibrium that has zero probability of costly war, a leader’s payoff net of audience costs cannot vary with their private information. After that, I identify the size of resource necessary to appease both states. If this necessary condition holds, which is affected by political bias, there exist properly specified audience costs that guarantee peaceful bargaining outcomes.

Misato Mitochondrial Distribution and Morphology Regulator 1 (MSTO1) is a soluble cytoplasmic protein that regulates mitochondrial dynamics by promoting mitochondrial fusion. Variants in the MSTO1 gene cause a rare disease characterized by early-onset myopathy and cerebellar ataxia, with almost 30 cases reported worldwide. Here we report a case of a 3-year-old boy with novel heterozygous variants of the MSTO1 gene (c.1A>G (p.M1?) and c.727G>C(p.Ala243Pro)). Sequencing data and subsequent validation show that the two variants were inherited from the mother and father of the patient (both were heterozygous). The clinical features are infancy-onset mental and motor retardation, language disorder, dysarthria, scoliosis, cerebellar atrophy, tremor, lower-extremity muscle weakness, elevated muscle enzymes, extensive myopathy with chronic atrophy, hyperventilation lungs, and previously unreported hairy back and enlarged gastrocnemius. Finally, novel heterozygous MSTO1 variants were discovered in this case, which expands the gene spectrum and clinical phenotype of this type of disease, and provides a new direction for future treatment and research. Then we summarize the mutational spectrum, pathological, clinical features and imaging of MSTO1 variants in a cohort of reported 31 patients and discuss the pathogenesis of MSTO1 in humans.

Traditionally, cancer-associated fibroblasts (CAFs), an essential component of tumor microenvironment, were exert a crucial part in colon cancer progression. In this study, single-cell RNA-sequencing (scRNA-seq) data from 23 and bulk RNA-seq data from 452 colon cancer patients were extracted from the GEO database and TCGA-COAD and GEO databases, respectively. From single-cell analysis, 825 differentially expressed genes (DEGs) in CAFs were identified between each pair of six newly defined CAFs, named enCAF, adCAF, vaCAF, meCAF, erCAF, and cyCAF. Cell communication analysis with the iTALK package showed communication relationship between CAFs, including cell autocrine, cytokine, and growth factor subtypes, such as receptor-ligand pairs of TNFSF14-LTBR, IL6-F3, and IL6-IL6ST. Herein, we demonstrated the presence and prognostic value of adCAF and erCAF in colon cancer based on CIBERSORTx, combining single-cell marker genes and transcriptomics data. The prognostic significance of the enCAF and erCAF has been indirectly proved by both the correlation analysis with macrophages and CAFs, and the quantitative reverse transcription-polymerase chain reaction (qRT-PCR) experiment based on 20 paired tumor samples. A prognostic model was constructed with 10 DEGs using the LASSO Cox regression method. The model was validated using two testing datasets, indicate a significant survival accuracy (p < 0.0025). Correlation analyses between clinical information, such as age, gender, tumor stage and tumor features (tumor purity and immune score), and risk scores revealed our CAF-related model’s robustness and excellent performance. Cell infiltration analysis by xCell revealed that the interaction between CAFs and multiple non-specific immune cells such as macrophages and the dendritic cell was a vital factor affecting immune score and prognosis. Finally, we analyzed how common anti-cancer drugs, including camptothecin, docetaxel and bortezomib, and immunotherapy, such as anti-PD-1 treatment, could be different in low-risk and high-risk patients inferred from our CAF-related model. In conclusion, the study utilized refined colon cancer fibroblast subsets and established the prognostic effects from the interaction with nonspecific immune cell.

Dyschromatosis symmetrica hereditaria (DSH), characterized by a mixture of hyper- and hypopigmented macules on the skin, is a rare pigmentary dermatosis of autosomal dominant inheritance. The pathogenic gene is adenosine deaminase acting on the RNA 1 gene (ADAR1), mutations in this gene also lead to Aicardi-Goutières syndrome type 6 (AGS 6), a rare hereditary encephalopathy with isolated spastic paraplegia. The pathomechanism of the ADAR1 gene mutations inducing DSH has not been clarified yet. We report the first case of DSH combined with AGS caused by the homozygous mutation of the ADAR1 gene in China (c.1622T > A) and reviewed the relevant literature. AGS 6 could occur in both men and women, and start in infancy. The main characteristics are growth retardation, skin depigmentation, intracranial calcification, and cerebral white matter lesions. In the current paper, the proband also had patent ductus arteriosus (PDA), ventricular septal defect (VSD), and mitral valve calcification, which are new symptoms that have not been reported in other cases. Additionally, we also aim to discuss the possible molecular mechanisms underlying the clinical heterogeneity caused by ADAR1 gene mutations.

BackgroundDermatomyositis is an autoimmune disease characterized by damage to the skin and muscles. CD4+ T cells are of crucial importance in the occurrence and development of dermatomyositis (DM). However, there are few bioinformatics studies on potential pathogenic genes and immune cell infiltration of DM. Therefore, this study intended to explore CD4+ T-cell infiltration–associated key genes in DM and construct a new model to predict the level of CD4+ T-cell infiltration in DM.MethodsGSE46239, GSE142807, GSE1551, and GSE193276 datasets were downloaded. The WGCNA and CIBERSORT algorithms were performed to identify the most correlated gene module with CD4+ T cells. Matascape was used for GO enrichment and KEGG pathway analysis of the key gene module. LASSO regression analysis was used to identify the key genes and construct the prediction model. The correlation between the key genes and CD4+ T-cell infiltration was investigated. GSEA was performed to research the underlying signaling pathways of the key genes. The key gene-correlated transcription factors were identified through the RcisTarget and Gene-motif rankings databases. The miRcode and DIANA-LncBase databases were used to build the lncRNA-miRNA-mRNA network.ResultsIn the brown module, 5 key genes (chromosome 1 open reading frame 106 (C1orf106), component of oligomeric Golgi complex 8 (COG8), envoplakin (EVPL), GTPases of immunity-associated protein family member 6 (GIMAP6), and interferon-alpha inducible protein 6 (IFI6)) highly associated with CD4+ T-cell infiltration were identified. The prediction model was constructed and showed better predictive performance in the training set, and this satisfactory model performance was validated in another skin biopsy dataset and a muscle biopsy dataset. The expression levels of the key genes promoted the CD4+ T-cell infiltration. GSEA results revealed that the key genes were remarkably enriched in many immunity-associated pathways, such as JAK/STAT signaling pathway. The cisbp_M2205, transcription factor-binding site, was enriched in C1orf106, EVPL, and IF16. Finally, 3,835 lncRNAs and 52 miRNAs significantly correlated with key genes were used to build a ceRNA network.ConclusionThe C1orf106, COG8, EVPL, GIMAP6, and IFI6 genes are associated with CD4+ T-cell infiltration. The prediction model constructed based on the 5 key genes may better predict the level of CD4+ T-cell infiltration in damaged muscle and lesional skin of DM. These key genes could be recognized as potential biomarkers and immunotherapeutic targets of DM.

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease (CTD), the main features of which are multiple serum autoantibodies and extensive involvement of multiple systems. The onset age of patients varies from childhood to middle age, with nearly 1/5 in childhood. Sjogren’s syndrome (SS) is also an autoimmune disease characterized by high-degree lymphocytic infiltration of exocrine glands, usually occurring in middle-aged and older women, and rarely in childhood. Neuromyelitis optica spectrum disorder (NMOSD) is an immune-mediated inflammatory demyelinating disease of the central nervous system (CNS) mainly involving the optic nerve and spinal cord. The coexistence of NMOSD and SLE and/or SS is well recognized by both neurologists and rheumatologists, but cases in children have been rarely reported. In this paper, we reported a case of a girl with onset at age 5 clinically featured by recurrent parotid gland enlargement, pancytopenia, hypocomplementemia, multiple positive serum antibodies, and cirrhosis. She was initially diagnosed with SS/SLE overlap syndrome at age 5. Four years later, the patient suffered a sudden vision loss and was examined to have positive AQP4 antibodies in serum and cerebrospinal fluid (CSF), and long segmental spinal swelling, in line with the diagnostic criteria for NMOSD. Up to now, the current patient is of the youngest onset age to develop SS/SLE coexisting with NMOSD, also with cirrhosis. It is important for clinicians to be aware of the possibility of CTDs coexisting with NMOSD in children, especially in those with positive anti-multiple autoantibodies, and to decrease the rate of missed diagnosis.

ObjectiveThe clinical manifestations of ataxia–telangiectasia (AT) are very complex and are easily misdiagnosed and missed. The purpose of this study was to explore the clinical characteristics and genetic features of five pediatric patients with AT from three pedigrees in china.MethodsRetrospectively collected and analyzed the clinical data and genetic testing results of five AT patients diagnosed by the Whole-exome sequencing followed by Sanger sequencing. The five patients with AT were from three pedigrees, including two female patients (case 1 and case 2) in pedigree I, one male patient (case 3) in pedigree II, and two male patients (case 4 and case 5) in pedigree III. According to the United Kingdom Association for Clinical Genomic Science Best Practice Guidelines for Variants Classification in Rare Disease 2020 to grade the genetic variants.ResultsFive patients had mainly clinical presentations including unsteady gait, dysarthria, bulbar conjunctive telangiectasia, cerebellar atrophy, intellectual disability, stunted growth, increase of alpha-fetoprotein in serum, lymphopenia. Notably, one patient with classical AT presented dystonia as the first symptom. One patient had recurrent infections, five patients had serum Immunoglobulin (Ig) A deficiency, and two patients had IgG deficiency. In three pedigrees, we observed five pathogenic variants of the ATM gene, which were c.1339C>T (p.Arg447Ter), c.7141_7151delAATGGAAAAAT (p.Asn2381GlufsTer18), c.437_440delTCAA (p.Leu146GlnfsTer6), c.2482A>T (p.Lys828Ter), and c.5495_5496+2delAAGT (p.Glu1832GlyfsTer4). Moreover, the c.437_440delTCAA, c.2482A>T, and c.5495_5496+2delAAGT were previously unreported variants.ConclusionsPediatric patients with classical AT may present dystonia as the main manifestation, or even a first symptom, besides typical cerebellar ataxia, bulbar conjunctive telangiectasia, etc. Crucially, we also found three novel pathogenic ATM gene variants (c.437_440delTCAA, c.2482A>T, and c.5495_5496+2delAAGT), expanding the ATM pathogenic gene mutation spectrum.

The non-invasive tissue adhesives with strong tissue adhesion and good biocompatibility are ideal for replacing traditional wound treatment methods such as sutures and needles. The self-healing hydrogels based on dynamic reversible crosslinking can recover their structure and function after damage, which is suitable for the application scenario of tissue adhesives. Herein, inspired by mussel adhesive proteins, we propose a facile strategy to achieve an injectable hydrogel (DACS hydrogel) by grafting dopamine (DOPA) onto hyaluronic acid (HA) and mixing it with carboxymethyl chitosan (CMCS) solution. The gelation time and rheological and swelling properties of the hydrogel can be controlled conveniently by adjusting the substitution degree of the catechol group and the concentration of raw materials. More importantly, the hydrogel exhibited rapid and highly efficient self-healing ability and excellent biodegradation and biocompatibility in vitro. Meanwhile, the hydrogel exhibited ~4-fold enhanced wet tissue adhesion strength (21.41 kPa) over the commercial fibrin glue. This kind of HA-based mussel biomimetic self-healing hydrogel is expected to be used as a multifunctional tissue adhesive material.

In heterogeneous image fusion problems, different imaging mechanisms have always existed between time-of-flight and visible light heterogeneous images which are collected by binocular acquisition systems in orchard environments. Determining how to enhance the fusion quality is key to the solution. A shortcoming of the pulse coupled neural network model is that parameters are limited by manual experience settings and cannot be terminated adaptively. The limitations are obvious during the ignition process, and include ignoring the impact of image changes and fluctuations on the results, pixel artifacts, area blurring, and the occurrence of unclear edges. Aiming at these problems, an image fusion method in a pulse coupled neural network transform domain guided by a saliency mechanism is proposed. A non-subsampled shearlet transform is used to decompose the accurately registered image; the time-of-flight low-frequency component, after multiple lighting segmentation using a pulse coupled neural network, is simplified to a first-order Markov situation. The significance function is defined as first-order Markov mutual information to measure the termination condition. A new momentum-driven multi-objective artificial bee colony algorithm is used to optimize the parameters of the link channel feedback term, link strength, and dynamic threshold attenuation factor. The low-frequency components of time-of-flight and color images, after multiple lighting segmentation using a pulse coupled neural network, are fused using the weighted average rule. The high-frequency components are fused using improved bilateral filters. The results show that the proposed algorithm has the best fusion effect on the time-of-flight confidence image and the corresponding visible light image collected in the natural scene, according to nine objective image evaluation indicators. It is suitable for the heterogeneous image fusion of complex orchard environments in natural landscapes.

In order to extract as much power as possible from the costly PV power system, the maximum power point tracking (MPPT) is necessary. It is well known that the output characteristics of PV array are nonlinear, the MPPT control scheme at same irradiation is easy because of there is only one maximum power point (MPP). However, the P–V output curves of the PV array display the multiple peaks with several local peaks (LPs) and one global peak (GP) at partial shading. Rapid fluctuation of the shading and improper physical constraint make the MPPT method difficult. Generally, there will exist several peaks due to the passing cloud, shading of buildings, dust, and excreta of passing birds. In this paper, a novel forecasting technology using the law of conservation of energy is proposed to roughly track the GP of a PV array which located in the adjacent area of accurate GP. The proposed strategy is easy to combine with the conventional MPPT method and rapidly gain the actual GP. Study results and experiment tests demonstrate that the proposed algorithm can perform on a real PV power system under uniform or complex irradiation conditions.

Summary: Amplification of ubiquitin E3 ligase Smurf1 promotes degradation of PTEN leading to hyperactivation of the Akt/mTORC1 pathway. However, inhibitors of this pathway have not hitherto yielded promising results in clinical studies because of strong drug resistance. Here, we investigated Smurf1 expression in various glioblastoma (GB) cell lines and patient tissues. The therapeutic efficacy of Smurf1 silencing and Torin1 treatment was assessed in GB cells and orthotopic mouse model. We found Smurf1 loss elevates PTEN levels that interrupt the epidermal growth factor receptor pathway activity. Cotreatment with Smurf1 silencing and mTORC1/C2 inhibitor Torin1 remarkably decreased phosphorylation of Akt, and mTORC1 downstream targets 4EBP1 and S6K resulting in synergistic inhibitory effects. Smurf1 knockdown in orthotopic GB mouse model impaired tumor growth and enhanced cytotoxicity of Torin1. Together, these findings suggest a rational combination of Smurf1 inhibition and Torin1 as a promising new avenue to circumvent PI3K/Akt pathway-driven tumor progression and drug resistance.

This article presents a model predictive control (MPC) coupled with an artificial potential field (APF) to resolve the trajectory tracking while considering the obstacle avoidance. In this article, the obstacle avoidance problem is solved by a local path planning based on the artificial potential field by constructing a virtual goal. A virtual goal is generated to produce an attractive force to guide the mobile robot to a collision-free space. The planned path is controlled by a proportional–integral–derivative (PID) controller to avoid collision. After arriving at the virtual goal, an off-line explicit MPC is calculated to obtain the optimal control inputs to track the reference trajectory. The simulation results show that the proposed method can be applied to control the mobile robot in the environment with one obstacle.

Alpha 7 nicotinic acetylcholine receptor (α7 nAChR) is critical for the pathogenesis of Escherichia coli (E. coli) K1 meningitis, a severe central nervous system infection of the neonates. However, little is known about how E. coli K1 manipulates α7 nAChR signaling. Here, through employing immortalized cell lines, animal models, and human transcriptional analysis, we showed that E. coli K1 infection triggers releasing of secreted Ly6/Plaur domain containing 1 (SLURP1), an endogenous α7 nAChR ligand. Exogenous supplement of SLURP1, combined with SLURP1 knockdown or overexpression cell lines, showed that SLURP1 is required for E. coli K1 invasion and neutrophils migrating across the blood-brain barrier (BBB). Furthermore, we found that SLURP1 is required for E. coli K1-induced α7 nAChR activation. Finally, the promoting effects of SLURP1 on the pathogenesis of E. coli K1 meningitis was significantly abolished in the α7 nAChR knockout mice. These results reveal that E. coli K1 exploits SLURP1 to activate α7 nAChR and facilitate its pathogenesis, and blocking SLURP1-α7 nAChR interaction might represent a novel therapeutic strategy for E. coli K1 meningitis.

Abstract Background Wilson's disease (WD) is a rare autosomal recessive inherited disorder that is induced by defects of the ATP7B gene and characterized by damage to the liver and nervous system caused by aberrant copper metabolism. The identification of pathogenic mutations on two homologous chromosomes has become the gold standard for the diagnosis of WD. Methods Sanger sequencing and multiplex ligation‐dependent probe amplification (MLPA) were combined to establish a genetic diagnosis for patients from 53 unrelated Chinese WD families. Results Biallelic mutations were detected by Sanger sequencing in 50 of the probands, while single heterozygous mutations were detected in the remaining three probands. A total of 45 diverse pathogenic mutations were detected, and 6 previously unreported mutations were involved. Five asymptomatic patients were screened from 85 family members of 38 probands participating in the study. Conclusion This study contributes to the enlargement of the mutational spectrum of the ATP7B gene among the population of China and highlights the significance of genetic testing for asymptomatic patients.

The present work investigates the coupling synchronization principle and stability in a vibrating system with two pairs counter-rotating unbalanced rotors (also called exciters). Based on Lagrange equations, the dimensionless coupling differential equations of motion of the system are deduced. The synchronization criterion of two pairs exciters stems from the averaging method, it satisfies the fact that the absolute value of dimensionless residual torque difference between arbitrary two driving motors is less than or equal to the maximum of their dimensionless coupling torques. The stability criterion of the synchronous states complies with Routh-Hurwitz principle. The coupling dynamic characteristics of the system are numerically analyzed in detail, including synchronization and stability ability, maximum of the coupling torque and phase relationship, etc. Some simulation results applying the Runge-Kutta algorithm are performed, it is shown that the motion states of the system can be classified into two types: sub-resonant state and super-resonant state. Generally in engineering, the ideal working points should be selected in sub-resonance region, in this case the expended energy can be saved relatively by 1/5–1/3, which is less than that in super-resonance region under the precondition of the same vibration amplitude value.

The tumor suppressor PTEN mainly inhibits the PI3K/Akt pathway in the cytoplasm and maintains DNA stability in the nucleus. The status of PTEN remains therapeutic effectiveness for chemoresistance of the DNA alkylating agent temozolomide (TMZ) in glioblastoma (GB). However, the underlying mechanisms of PTEN’s interconnected role in the cytoplasm and nucleus in TMZ resistance are still unclear. In this study, we report that TMZ-induced PTEN nuclear import depends on PTEN ubiquitylation modification by Smurf1. The Smurf1 suppression decreases the TMZ-induced PTEN nuclear translocation and enhances the DNA damage. In addition, Smurf1 degrades cytoplasmic PTEN K289E (the nuclear-import-deficient PTEN mutant) to activate the PI3K/Akt pathway under TMZ treatment. Altogether, Smurf1 interconnectedly promotes PTEN nuclear function (DNA repair) and cytoplasmic function (activation of PI3K/Akt pathway) to resist TMZ. These results provide a proof-of-concept demonstration for a potential strategy to overcome the TMZ resistance in PTEN wild-type GB patients by targeting Smurf1.

The high-grade glioma is characterized by cell heterogeneity, gene mutations, and poor prognosis. The deletions and mutations of the tumor suppressor gene PTEN (5%-40%) in glioma patients are associated with worse survival and therapeutic resistance. Characterization of unique prognosis molecular signatures by PTEN status in glioma is still unclear. This study established a novel risk model, screened optimal prognostic signatures, and calculated the risk score for the individual glioma patients with different PTEN status. Screening results revealed fourteen independent prognostic gene signatures in PTEN-wt and three in the -50PTEN-mut subgroup. Moreover, we verified risk score as an independent prognostic factor significantly correlated with tumor malignancy. Due to the higher malignancy of the PTEN-mut gliomas, we explored the independent prognostic signatures (CLCF1, AEBP1, and OS9) for a potential therapeutic target in PTEN-mut glioma. We further separated IDH wild-type glioma patients into GBM and LGG to verify the therapeutic target along with PTEN status, notably, the above screened therapeutic targets are also significant prognostic genes in both IDH-wt/PTEN-mut GBM and LGG patients. We further identified the small molecule compound (+)-JQ1 binds to all three targets, indicating a potential therapy for PTEN-mut glioma. In sum, gene signatures and risk scores in the novel risk model facilitate glioma diagnosis, prognosis prediction, and treatment.

X-linked sideroblastic anemia with ataxia (XLSA/A) is a rare X-liked inherited disease, which was linked to the ABCB7 gene mutations. So far, five families have been reported worldwide. We present the first Chinese family of XLSA/A with novel ABCB7 gene mutation (c.2024A > G) and make a retrospective literature review. All affected patients were male. Age of symptom onset was

Nucleotide oligomerization domain-like receptors (NLRs), a class of pattern recognition receptors, participate in the host’s first line of defense against invading pathogenic microorganisms. NLR family caspase recruitment domain containing 5 (NLRC5) is the largest member of the NLR family and has been shown to play an important role in inflammatory processes, angiogenesis, immunity, and apoptosis by regulating the nuclear factor-κB, type I interferon, and inflammasome signaling pathways, as well as the expression of major histocompatibility complex I genes. Recent studies have found that NLRC5 is also associated with neuronal development and central nervous system (CNS) diseases, such as CNS infection, cerebral ischemia/reperfusion injury, glioma, multiple sclerosis, and epilepsy. This review summarizes the research progress in the structure, expression, and biological characteristics of NLRC5 and its relationship with the CNS.

Purpose: To evaluate the clinical differences between pediatric and adult patients with myelin oligodendrocyte glycoprotein antibody-associated encephalomyelitis (MOG-EM).Methods: We retrospectively reviewed the clinical features of pediatric and adult patients with MOG-EM in our center between November 2015 and October 2020.Results: Twenty-eight pediatric patients and 25 adults were admitted to our study. Bilateral optic neuritis (BON) was the most common initial phenotype in the pediatric group but less common in the adult group (28.57 vs. 0%, p = 0.0119). Almost half of the adult patients presented with neuromyelitis optica spectrum disease (NMOSD), which was less prevalent among the pediatrics (48 vs. 21.43%, p = 0.0414). Visual impairment was the most common symptom in both groups during the initial attack (pediatric group, 39.29%; adult group, 64%) and throughout the full course (pediatric group, 57.14%; adult group, 72%). More pediatric patients suffered from fever than adult patients at onset (pediatric group, 28.57%; adult group, 4%; p = 0.0442) and throughout the full course (pediatric group, 39.29%; adult group, 12%; p = 0.0245). Multiple patchy lesions in subcortical white matter (pediatric group, 40.74%; adult group, 45%), periventricular (pediatric group, 25.93%; adult group, 35%), infratentorial (pediatric group, 18.52%; adult group, 30%) and deep gray matter (pediatric group, 25.93%; adult group, 20%) were frequent in all cases, no significant difference was found between the two groups, while bilateral optic nerve involvement was more frequent in pediatric group (61.54 vs. 14.29%, p = 0.0042) and unilateral optic nerve involvement was higher in adult group (64.29 vs. 15.38%, p = 0.0052). At the last follow-up, adult patients had a higher average EDSS score (median 1.0, range 0–3) than pediatrics (median 0.0, range 0–3), though not significant (p = 0.0752). Patients aged 0–9 years (61.54%) and 10–18 years (70%), and patients presenting with encephalitis/meningoencephalitis (100%) and ADEM (75%) were more likely to recover fully.Conclusions: Visual impairment was the dominant symptom in both pediatric and adult patients, while fever was more frequent in pediatric patients. Data suggested that BON and bilateral optic nerve involvement were more common in pediatric cases whereas NMOSD and unilateral optic nerve involvement were more prevalent in adults. The younger patients and patients presenting with encephalitis/meningoencephalitis and ADEM tended to recover better.

Glioblastoma (GB) is the most malignant and aggressive form of brain tumor, characterized by frequent hyperactivation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. PI3K/AKT/mTOR inhibitors have a promising clinical efficacy theoretically. However, strong drug resistance is developed in GB against the PI3K/AKT/mTOR inhibitors due to the cytoprotective effect and the adaptive response of autophagy during the treatment of GB. Activation of autophagy by the PI3K/AKT/mTOR inhibitors not only enhances treatment sensitivity but also leads to cell survival when drug resistance develops in cancer cells. In this review, we analyze how to increase the antitumor effect of the PI3K/AKT/mTOR inhibitors in GB treatment, which is achieved by various mechanisms, among which targeting autophagy is an important mechanism. We review the dual role of autophagy in both GB therapy and resistance against inhibitors of the PI3K/AKT/mTOR signaling pathway, and further discuss the possibility of using combinations of autophagy and PI3K/AKT/mTOR inhibitors to improve the treatment efficacy for GB. Finally, we provide new perspectives for targeting autophagy in GB therapy.

Glioblastoma (GBM) is highly invasive and the deadliest brain tumor in adults. It is characterized by inter-tumor and intra-tumor heterogeneity, short patient survival, and lack of effective treatment. Prognosis and therapy selection is driven by molecular data from gene transcription, genetic alterations and DNA methylation. The four GBM molecular subtypes are proneural, neural, classical, and mesenchymal. More effective personalized therapy heavily depends on higher resolution molecular subtype signatures, combined with gene therapy, immunotherapy and organoid technology. In this review, we summarize the principal GBM molecular classifications that guide diagnosis, prognosis, and therapeutic recommendations.

Glioblastoma (GB) is the most common and aggressive brain malignancy, characterized by heterogeneity and drug resistance. PTEN, a crucial tumor suppressor, exhibits phosphatase-dependent (PI3K-AKT-mTOR pathway)/independent (nucleus stability) activities to maintain the homeostatic regulation of numerous physiological processes. Premature and absolute loss of PTEN activity usually tends to cellular senescence. However, monoallelic loss of PTEN is frequently observed at tumor inception, and absolute loss of PTEN activity also occurs at the late stage of gliomagenesis. Consequently, aberrant PTEN homeostasis, mainly regulated at the post-translational level, renders cells susceptible to tumorigenesis and drug resistance. Ubiquitination-mediated degradation or deregulated intracellular localization of PTEN hijacks cell growth rheostat control for neoplastic remodeling. Functional inactivation of PTEN mediated by the overexpression of ubiquitin ligases (E3s) renders GB cells adaptive to PTEN loss, which confers resistance to EGFR tyrosine kinase inhibitors and immunotherapies. In this review, we discuss how glioma cells develop oncogenic addiction to the E3s-PTEN axis, promoting their growth and proliferation. Antitumor strategies involving PTEN-targeting E3 ligase inhibitors can restore the tumor-suppressive environment. E3 inhibitors collectively reactivate PTEN and may represent next-generation treatment against deadly malignancies such as GB.

Congenital myasthenic syndrome (CMS) is a group of genetic disorders of neuromuscular transmission that is characterized by muscle weakness. A mutation in the gene encoding agrin (AGRN) is a rare cause of CMS, and only a few families or isolated cases have been reported. We reported a pediatric proband exhibiting muscle weakness in the trunk and limbs with skeletal malformation and intellectual disability and performed whole-exome sequencing (WES) of the proband parent-offspring trio. Results revealed a new compound heterozygous mutation in AGRN: c.125A>C (p.Glu42Ala) in the N-terminal agrin domain (NtA) and c.4516G>A (p.Ala1506Thr) in the laminin G1 domain (LG1). Bioinformatic analysis predicted the mutation as possibly pathogenic. The new compound heterozygous mutation in AGRN may disrupt agrin's known function of bridging laminin and α-dystroglycan and undermine the formation and maintenance of the neuromuscular junction (NMJ) via both muscular and neural agrin pathways. It may also induce secondary peripheral neuropathy and skeletal malformation.

Infant formula incidents have endangered the dietary safety and healthy growth of infants and young children and are triggers of the public’s negative emotions, attracting widespread public attention. The aim of this research was to explore how perceived knowledge gap, risk perception, past actual risk experience, and media risk experience affect anxiety. The research data obtained from 506 respondents were divided into groups with actual risk experience and without actual risk experience. Then, PLS-SEM was used to analyze the data. The results show that risk perception mediated the relationship between perceived knowledge gap and anxiety. Specifically, for the group with actual risk experience, perceived knowledge gap had a significant direct impact on anxiety; however, there was no moderation effect of media experience on the relationship between perceived knowledge gap and risk perception. For the group without actual risk experience, perceived knowledge gap had no direct effect on anxiety, and media experience had a significant moderating effect on the relationship between perceived knowledge gap and risk perception. The results suggest that in infant formula safety incidents, actual risk experience and media risk experience have different influence mechanisms on anxiety. Actual risk experience will directly and intuitively bridge the relationship between perceived knowledge gap and anxiety. Meanwhile, groups without actual risk experience tend to be influenced by rational risk judgment, and this process is moderated by media risk experience.

Abstract In order to improve the effectiveness of intrusion detection, an intrusion detection method of the Internet of Things (IoT) is proposed by suppressed fuzzy clustering (SFC) algorithm and principal component analysis (PCA) algorithm. In this method, the data are classified into high-risk data and low-risk data at first, which are detected by high frequency and low frequency, respectively. At the same time, the self-adjustment of the detection frequency is carried out according to the suppressed fuzzy clustering algorithm and the principal component analysis algorithm. Finally, the key factors influencing the algorithm are analyzed deeply by simulation experiment. The results shows that, compared to traditional method, this method has better adaptability.

Background and objective Since 1970s, Xuanwei in Yunnan province has been one of the towns with highest lung cancer mortality in China. Moreover, the characters of high female lung cancer mortality and sub-regional clustering high lung cancer mortality have not changed. In this study, we further described the exposure situation of risk factors of lung cancer in Xuanwei nowadays, in order to explore the trend of the distribution of lung cancer there. Methods Firstly we divided the 26 towns of Xuanwei city to high-, median- and low- lung cancer areas by the lung cancer mortality in 2010-2012. We chose 2 towns within each area according to topography and orientation, and randomly picked 4 villages in each town to be our study area. We did a questionnaire about lung cancer related risk factors upon the sample population in the study area. We calculated the exposure percentages of each risk factor, in whole sample population and subgroups, for nowadays and for 10 years ago (only living environmental risk factors), and compared them between areas or time points using standardized rates and the statistical test of standardized rate comparison, or chi-square test. Results 65%-80% male in the study area has a history of smoking; 60%-90% non-smoker has been exposed to second hand smoke. These situations are worse in high and median lung cancer areas. 50% male in median lung cancer area have coal mining work experience, which is 2 times of the percentages in the other two areas; while 15%-25% people in high lung cancer area have other occupational exposure history to particulate air pollution, which is 3-5 times of the percentages in the other two areas. From ten years ago until nowadays, 80% families in median lung cancer area use 2 tons or more smoky coal per year; more than 90% families burn coal for household heating; more than 60% families suffer from smog in the kitchen during cook; 60% families most frequently use stove in the ground with chimney. Only 20% families in high lung cancer area now use 2 tons or more smoky coal per year. Now 50%-75% families in the study area use 700 kilowatt-hours of electricity per year, much more than ten years ago. 80% residents in low lung cancer area eat fatty or pickled or smoked food at least 3 days per week; while in high and median lung cancer areas the percentages are 50%-60%. Conclusion According to data obtained in this survey, current distribution of smoky coal use has differed from the distribution of high-, median- and low- lung cancer areas. Tobacco use and second hand smoke, the use of smoky coal and occupational exposure to particulate matters could be the main risk factors for lung cancer in Xuanwei now. The relations between lung cancer and stove type, dietary habit and so on deserve further study.

This paper proposes an improved Harmony Search algorithm, and gives the definition of the Global Sharing Factor of the Harmony Search (HS) algorithm. In the definition, the number of creations of the HS algorithm is applied to the sharing factor and calculated. In this algorithm, the natural harmony encoding method is used to encode the initial harmony, and the total path length of all vehicles is taken as the optimization objective function. A new harmony generation strategy is proposed as follows: each tone component in an evolution is calculated separately using the new learning strategy and update strategy. In the calculation process, the tone component is judged by whether it needs to be adjusted according to the adjustment strategy. In this way, the problems of singularity and randomness of the new harmony generation strategy of basic HS are solved to improve the diversity of algorithm solutions. Then, a new Harmony Search method with Global Sharing Factor based on natural number coding and decoding for the Vehicle Routing Problem (GSF-HS-VRP) is proposed. The improved Global Sharing Factor-Harmony Search-Vehicle Routing Problem (GSF-HS-VRP) algorithm is applied to capacity-limited vehicle path optimization problems compared with the HS, Improved Harmony Search (IHS), Global-best Harmony Search (GHS), and Self-adaptive Global Best Harmony Search (SGHS) algorithms. The small-scale data and Solomon examples were adopted as the experimental data. Compared with the other four algorithms, the GSF-HS-VRP algorithm has the shortest running time, more rapid convergence speed, and higher efficiency. In the multi-vehicle test, with the increase of the number of vehicles, the optimized path of the vehicle is more satisfied in relation to the actual needs of customers. The results showed that this method could effectively improve the optimization performance of the capacity-limited vehicle routing problem.

Background Xuanwei is one of the towns with highest lung cancer mortality in China. Residents there frequently use smoky coal for domestic cooking and heating. The smoking prevalence there is also high. Methods We conducted a population-based case-control study. 388 lung cancer cases and 388 gender-age-area-matched controls were surveyed. The exposure levels to potential lung cancer risk factors of multi-aspects 10 years ago were collected. After checking Spearman correlations between variables and referring to previous studies, we built conditional logistic regression model adjusting education, family history of malignancy, diet, alcohol consumption, occupational history, housing type and exposure to second hand smoke. We then introduced household annual consumption of smoky coal and total consumption of cigarettes from born to 10 years ago to the model in the form of ordered categorical variable (coal level 1-3: never use, less than 3 tons per year, 3 tons or more per year; tobacco level 1-3: never use, less than 130 thousands cigarettes, 130 thousands or more cigarettes). Results There were 27% and 31.2% ever-smokers in case and control group, respectively. Without interactive item, the effect of tobacco use on lung cancer was (all comparing with level 1, with 95% confidence intervals) level 2: OR=0.90(0.22, 3.67), level 3: OR=1.59(0.45, 5.70). After adding interactive item of coal and tobacco in the model, the effect of tobacco use among people never used smoky coal was level2: OR=1.09(0.09, 13.78), level3: OR=2.20(0.16, 29.44); among people using relatively small amount of coal was level2: OR=0.59(0.03, 11.37), level3: OR=0.18(0.01, 4.82); among people using large amount of coal was level2: OR=0.93(0.32, 2.72), level3: OR=1.78(0.30, 10.67). Household annual amount of smoky coal used, 10 years ago Total consumption of cigarettes from born to 10 years ago (reference group: never smoker) β SE OR(95%CI) Never

Kaposi’s sarcoma-associated herpesvirus (KSHV) is a tumor virus and the etiologic agent of Kaposi’s Sarcoma (KS). KSHV G protein-coupled receptor (vGPCR) is an oncogene that is implicated in malignancies associated with KHSV infection. In this study, we show that vGPCR undergoes extensive N-linked glycosylation within the extracellular domains, specifically asparagines 18, 22, 31 and 202. An immunofluorescence assay demonstrates that N-linked glycosylation are necessary for vGPCR trafficking to the cellular membrane. Employing vGPCR mutants whose glycosylation sites were ablated, we show that these vGPCR mutants failed to activate downstream signaling in cultured cells and were severely impaired to induce tumor formation in the xenograph nude mouse model. These findings support the conclusion that glycosylation is critical for vGPCR tumorigenesis and imply that chemokine regulation at the plasma membrane is crucial for vGPCR mediated signaling.

Aiming at the low recognition effect of apple images captured in a natural scene, and the problem that the OTSU algorithm has a single threshold, lack of adaptability, easily caused noise interference, and over-segmentation, an apple image recognition multi-objective method based on the adaptive harmony search algorithm with simulation and creation is proposed in this paper. The new adaptive harmony search algorithm with simulation and creation expands the search space to maintain the diversity of the solution and accelerates the convergence of the algorithm. In the search process, the harmony tone simulation operator is used to make each harmony tone evolve towards the optimal harmony individual direction to ensure the global search ability of the algorithm. Despite no improvement in the evolution, the harmony tone creation operator is used to make each harmony tone to stay away from the current optimal harmony individual for extending the search space to maintain the diversity of solutions. The adaptive factor of the harmony tone was used to restrain random searching of the two operators to accelerate the convergence ability of the algorithm. The multi-objective optimization recognition method transforms the apple image recognition problem collected in the natural scene into a multi-objective optimization problem, and uses the new adaptive harmony search algorithm with simulation and creation as the image threshold search strategy. The maximum class variance and maximum entropy are chosen as the objective functions of the multi-objective optimization problem. Compared with HS, HIS, GHS, and SGHS algorithms, the experimental results showed that the improved algorithm has higher a convergence speed and accuracy, and maintains optimal performance in high-dimensional, large-scale harmony memory. The proposed multi-objective optimization recognition method obtains a set of non-dominated threshold solution sets, which is more flexible than the OTSU algorithm in the opportunity of threshold selection. The selected threshold has better adaptive characteristics and has good image segmentation results.

To achieve effective and accurate optimization for multi-objective optimization problems, a multi-objective artificial bee colony algorithm with regulation operators (RMOABC) inspired by the intelligent foraging behavior of honey bees was proposed in this paper. The proposed algorithm utilizes the Pareto dominance theory and takes advantage of adaptive grid and regulation operator mechanisms. The adaptive grid technique is used to adaptively assess the Pareto front maintained in an external archive and the regulation operator is used to balance the weights of the local search and the global search in the evolution of the algorithm. The performance of RMOABC was evaluated in comparison with other nature inspired algorithms includes NSGA-II and MOEA/D. The experiments results demonstrated that the RMOABC approach has better accuracy and minimal execution time.