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The size of datasets is growing exponentially as information technology advances, and it is becoming more and more crucial to provide efficient learning algorithms for neural networks to handle massive amounts of data. Due to their potential for handling huge datasets, feed-forward neural networks with random weights (FNNRWs) have drawn a lot of attention. In this paper, we introduced an efficient feed-forward neural network scheme (FNNS) for processing massive datasets with random weights. The FNNS divides large-scale data into subsets of the same size, and each subset derives the corresponding submodel. According to the activation function, the optimal range of input weights and biases is calculated. The input weight and biases are randomly generated in this range, and the iterative scheme is used to evaluate the output weight. The MNIST dataset was used as the basis for experiments. The experimental results demonstrate that the algorithm has a promising future in processing massive datasets.

Cervical cancer is one of the most severe and prevalent female malignancies and a global health issue. The molecular mechanisms underlying cervical cancer development are poorly investigated. As a type of extracellular membrane vesicles, EVs from cancer cells are involved in cancer progression by delivering regulatory factors, such as proteins, microRNAs (miRNAs), and long non-coding RNAs (lncRNAs). In this study, we identified an innovative function of extracellular vesicle (EV) lncRNA AGAP2-AS1 in regulating cervical cancer cell proliferation. The EVs were isolated from the cervical cancer cells and were observed by transmission electron microscopy (TEM) and were confirmed by analyzing exosome markers. The depletion of AGAP2-AS1 by siRNA significantly reduced its expression in the exosomes from cervical cancer and in the cervical cancer treated with AGAP2-AS1-knockdown exosomes. The expression of AGAP2-AS1 was elevated in the clinical cervical cancer tissues compared with the adjacent normal tissues. The depletion of EV AGAP2-AS1 reduced cell viabilities and Edu-positive cervical cancer cells, while it enhanced cervical cancer cell apoptosis. Tumorigenicity analysis in nude mice showed that the silencing of EV AGAP2-AS1 attenuated cervical cancer cell growth in vivo. Regarding the mechanism, we identified that AGAP2-AS1 increased SIRT1 expression by sponging miR-3064-5p in cervical cancer cells. The overexpression of SIRT1 or the inhibition of miR-3064-5p reversed EV AGAP2-AS1 depletion-inhibited cancer cell proliferation in vitro. Consequently, we concluded that EV lncRNA AGAP2-AS1 contributed to cervical cancer cell proliferation through regulating the miR-3064-5p/SIRT1 axis. The clinical values of EV lncRNA AGAP2-AS1 and miR-3064-5p deserve to be explored in cervical cancer diagnosis and treatments.

Background Diet, environment, and genomic context have a significant impact on humans’ intestinal microbiota. Moreover, migration may be accompanied by changes in human eating habits and living environment, which could, in turn, affect the intestinal microbiota. Located in southwestern China, Tibet has an average altitude of 4,000 meters and is known as the world’s roof. Xianyang is situated in the plains of central China, with an average altitude of about 400 meters. Methods To understand the association between intestinal microbiota and population migration, we collected the fecal samples from 30 Tibetan women on the first day (as TI1st), six months (as TI2nd), and ten months (as TI3rd) following migration from Tibet to Xianyang. Fecal samples were collected from 29 individuals (belonging to the Han women) as a control. The dietary information of the Tibetan women and the Han women was gathered. We performed a 16S rRNA gene survey of the collected fecal samples using Illumina MiSeq sequencing. Results Following the migration, the alpha and beta diversity of Tibetan women’s intestinal microbiota appeared unaffected. Linear discriminant analysis effect size (LEfSe) analysis showed that Klebsiella, Blautia, and Veillonella are potential biomarkers at TI1st, while Proteobacteria and Enterobacteriaceae were common in TI3rd. Finally, functional prediction by phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) found no significant up-regulation or down-regulation gene pathway in the intestinal microbiota of Tibetan women after migration. The present study reveals that the higher stability in Tibetan women’s intestinal microbiota was less affected by the environment and diet, indicating that Tibetan women’s intestinal microbiota is relatively stable. The main limitations of the study were the small sample size and all volunteers were women.

Stroke remains the leading cause of long-term disability worldwide with significant long-term sequelae. However, there is no highly effective treatment to enhance post-stroke recovery despite extensive efforts in exploring rehabilitative therapies. Neurorehabilitation is recognized as the cornerstone of functional restoration therapy in stroke, where treatments are focused on neuroplastic regulation to reverse neural structural disruption and improve neurofunctional networks. Post-stroke neuroplasticity changes begin within hours of symptom onset and reaches a plateau by 3 to 4 weeks within the global brain in animal studies. It plays a determining role in spontaneous stroke recovery. Microglia are immediately activated following cerebral ischemia, which has been found both proximal to the primary ischemic injury and at the remote brain regions which have functional connections to the primary injury area. Microglia exhibit different activation profiles based on the microenvironment and adaptively switch their phenotypes in a spatiotemporal manner in response to brain injuries. Microglial activation coincides with neuroplasticity after stroke, which provides the fundamental base for the microglia-mediated inflammatory responses involved in the entire neural network rewiring and brain repair. Microglial activation exerts important effects on spontaneous recovery after stroke, including structural and functional reestablishment of neurovascular networks, neurogenesis, axonal remodeling, and blood vessel regeneration. In this review, we focus on the crosstalk between microglial activation and endogenous neuroplasticity, with a special focus on the plastic alterations in the whole brain network and their implications for structural and functional restoration after stroke. We then summarize recent advances in the impacts of microglial phenotype polarization on brain plasticity, trying to discuss the potential efficacy of microglia-based extrinsic restorative interventions in promoting post-stroke recovery.

Background: Dexamethasone (DEX) is widely adopted to reduce tumor-associated edema in glioblastoma (GBM) patients despite its side effects. However, the benefits of using DEX in GBM patients remains elusive.Methods: In this study, we performed a comprehensive meta-analysis to address this concern. We searched the relevant studies from PubMed, Web of Science, and EMBASE databases, and then applied random or fixed-effects models to generate estimated summary hazard radios (HRs) and the 95% confidence intervals (CIs). Moreover, subgroup and sensitivity analysis were conducted and publication bias were further evaluated.Results: Ten articles with a total of 2,230 GBM patients were eligible according to the inclusion criteria. In the assessment of overall survival (OS), meta-analysis data revealed that DEX was significantly associated with the poor prognosis of GBM patients (HR=1.44, 95% CI=1.32−1.57). In the progression-free survival (PFS), the pooled results indicated that the use of DEX can increase 48% death risk for GBM patients (HR=1.48, 95% CI=1.11−1.98). Subgroup analyses revealed that DEX was associated with poorer outcome of GBM in subgroup of newly diagnosed patients and GBM patients treated with ≥ 2mg/day. Sensitivity analyses showed that no study changed the pooled results materially for both OS and PFS analyses. The funnel plot had no obvious asymmetry.Conclusion: Our findings partly confirmed that use of DEX was associated with poor treatment outcome in GBM patients. To reach a definitive conclusion, large samples from multi-centers are urgent to address this concern.

This research aims to analyze the correlation between human papillomavirus (HPV) infection and ovarian epithelial cancer based on exponential distribution mathematical model, so as to provide an experimental basis for the early diagnosis of ovarian epithelial cancer by magnetic resonance imaging (MRI) in the future. In this study, 124 patients with ovarian epithelial cancer tissues pathologically confirmed in our hospital from March 31, 2017 to February 20, 2019 were selected as the experimental group, and 64 patients with normal ovarian tissues were selected as the control group, and the positive rate of HPV infection was detected by the computer cell test (CCT) system. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was constructed and adopted to analyze the scanning images. The correlation between HPV infection and pathological type, clinical stage, tissue differentiation degree, and CA125 in serum was studied by exponential distribution mathematical model. The results showed that the positive rate of HPV infection in the ovarian tissues of the experimental group was significantly higher than that of the control group (P

Objectives: A multidrug-resistant strain of the opportunistic pathogen Streptococcus sanguis (S28) was isolated from a throat swab of a child with scarlet fever as a rare case. Genome sequencing and analysis of strain S28 were performed to gain a better understanding of the multidrug resistance mechanisms of S. sanguis and its relationship with scarlet fever. Methods: The genome of S. sanguis S28 was sequenced on a Illumina HiSeq platform. Genome assembly was conducted using SOAPdenovo v.2.04 and the assembled genome sequence was submitted to NCBI for annotation. Results: The 1 268 358 696 bp genome of S. sanguis S28 contains 2287 coding sequences (CDS) with a GC content of 43.2%. Strain S28 possesses four antimicrobial resistance genes (ARGs), which is consistent with phenotypic analysis. A novel transposon with three genes conferring resistance to macrolide–lincosamide–streptogramin B (MLSB) antibiotics, tetracyclines and aminoglycosides was discovered. Conclusion: To our knowledge, this is the first report of a S. sanguis genome isolated from a throat swab of a child with scarlet fever and the first report of a transposon with three activated ARGs conferring resistance to MLSB, tetracyclines and aminoglycosides together.

Abstract Background Several studies on the growth rates of abdominal aortic aneurysm (AAA) in Chinese population have been conducted; however, this issue remains unclear. The aim of this study is to systematically review published data of the AAA growth rates among people in China. Methods We conducted a comprehensive search of multiple databases to identify all studies of AAA growth in the Chinese population from inception until June 2017. AAA growth rates were combined to yield the growth rates at specified aneurysm diameter ranges, with using a random-effects model or fixed-effects model according to heterogeneity. Results A total of 8257 studies were initially identified and only 4 studies were eventually included. A random-effects analysis showed that the growth rates of AAA in Chinses population is ranging from 0.18 cm/year to 0.75 cm/year. The pooled mean growth rates among individuals with aneurysm measuring 3.0–3.9 cm, 4.0–5.9 cm and ≧ 6.0 cm in diameter were 0.21 cm/year (95% CI: 0.19 cm/year to 0.23 cm/year), 0.38 cm/year (95% CI: 0.33 cm/year to 0.43 cm/year), and 0.71 cm/year (95% CI: 0.64 cm/year to 0.77 cm/year) respectively. Further analysis found that the pooled mean growth rates for individuals with small AAA (diameters measuring 3.0–4.9 cm) was 0.28 cm/year (95% CI: − 0.06 cm/year to 0.61 cm/year)`and for individuals with large AAA (diameters ≥5.0 cm) was 0.75 cm/year (95% CI: 0.20 cm/year to 1.3 cm/year). Finally, meta-regression showed a strong trend of linear relationship between AAA growth rate and aneurysm diameter. Conclusions The growth rates of AAA in the Chinese population increase with AAA enlargement and appear to range from 0.18 cm/year in the smallest AAAs to 0.75 cm/year when the diameter exceeds 6 cm. However, based on current studies, it is difficult to estimate the accurate average AAA growth rate in Chinese patients. More large-scale, high-quality studies are required to achieve that. Overall, AAA growth rate increase with increased aneurysm diameter.

Abstract Gastric cancer (GC) is one of the leading causes of cancer-related death in both men and women due to delayed diagnosis and high metastatic frequency. Extracellular vesicles (EVs) are membrane-bound nanovesicles which are released by cells into body fluids such as plasma, saliva, breast milk, cerebrospinal fluid, semen, urine, lymphatic fluid, amniotic fluid, sputum and synovial fluid. EVs deliver almost all types of biomolecules such as proteins, nucleic acids, metabolites, and even pharmacological compounds. These bioactive molecules can be delivered to recipient cells to influence their biological properties, modify surrounding microenvironment and distant targets. The extensive exploration of EVs enhances our comprehension of GC biology referring to tumor growth, metastasis, immune response and evasion, chemoresistance and treatment. In this review, we will sum up the effects of GC-derived EVs to the tumor microenvironment. Moreover, we will also summarize the function of microenvironment-derived EVs in GC and discuss how the bidirectional communication between tumor and microenvironment affect GC growth, metastatic behavior, immune response, and drug resistance. At last, we prospect the clinical application viewpoint of EVs in GC.

Hexokinase (HXK) family proteins exert critical roles in catalyzing hexose phosphorylation, sugar sensing, and modulation of plant growth and stress adaptation. Nevertheless, a large amount remains unknown about the molecular profile of HXK enzymes in Populus trichocarpa, a woody model tree species. A genome-wide survey of HXK-encoding genes, including phylogenies, genomic structures, exon/intron organization, chromosomal distribution, and conserved features, was conducted, identifying six putative HXK isogenes (PtHXK1-6) in the Populus genome. The evolutionary tree demonstrated that 135 homologous HXKs between 17 plant species were categorized into four major subfamilies (type A, B, C, and D), clustering one plastidic (PtHXK3) and five mitochondrial PtHXKs grouped into type A and B, respectively. The in silico deduction prompted the presence of the conserved sugar-binding core (motif 4), phosphorylation sites (motif 2 and 3), and adenosine-binding domains (motif 7). The transcriptomic sequencing (RNA-seq) and the quantitative real-time PCR (qRT-PCR) assays revealed that three isogenes (PtHXK2, 3, and 6) were abundantly expressed in leaves, stems, and roots, while others appeared to be dominantly expressed in the reproductive tissues. Under the stress exposure, PtHXK2 and 6 displayed a significant induction upon the pathogenic fungi (Fusarium solani) infection and marked promotions by glucose feeding in roots. In contrast, the PtHXK3 and 6 are ABA-responsive genes, following a dose-dependent manner. The comprehensive analyses of the genomic patterns and expression profiling provide theoretical clues and lay a foundation for unraveling the physiological and signaling roles underlying the fine-tuned PtHXKs responding to diverse stressors.

Promoting agricultural green growth has become an indispensable key content to speed up the process of agricultural modernization, has become a necessary prerequisite to achieve common prosperity of the rural people, and has become the basic practice of implementing people-centered development thought in the stage of high-quality development. Many researchers have studied the problems, level measurement and route choice of the growth of agriculture. However, there have been few studies on how to promote the agricultural green growth from the perspective of agricultural modernization, and how to combine the green agricultural GDP with the agricultural green total factor productivity (GTFP). To address this research inadequacy, in this paper, we focus on the time and space comparison of green agricultural GDP, agricultural GTFP, and their source decomposition, and summarize and discuss the key factors affecting agricultural GTFP. The results show that the share of output value of green agriculture in Tongren City is relatively high within the region of the province, and there is a large temporal and spatial difference between the change of agricultural GTFP and agricultural technology utilization efficiency and agricultural technology progress. At the same time, the improvement of economic development level can significantly promote the rise of agricultural GTFP, agricultural technology utilization efficiency, and agricultural technology progress. On balance, our results compare green agricultural GDP, agricultural GTFP, and their source decomposition in time and space, and reveals their evolution law and development trend from the perspective of high-quality development of agricultural modernization. In this way, we can provide an empirical basis and decision-making reference for accelerating the high-quality development of agricultural modernization.

Traditional analytical methods for thalassemia screening are needed to process complicated and time-consuming sample pretreatment. In recent decades, ambient mass spectrometry (MS) approaches have been proven to be an effective analytical strategy for direct sample analysis. In this work, we applied ambient MS with wooden-tip electrospray ionization (WT-ESI) for the direct analysis of raw human blood samples that were pre-identified by gene detection. A total of 319 whole blood samples were investigated in this work, including 100 α-thalassemia carriers, 67 β-thalassemia carriers, and 152 control healthy samples. Only one microliter of raw blood sample was directly loaded onto the surface of the wooden tip, and then five microliters of organic solvent and a high voltage of +3.0 kV were applied onto the wooden tip to generate spray ionization. Multiply charged ions of human hemoglobin (Hb) were directly observed by WT-ESI-MS from raw blood samples. The signal ratios of Hb chains were used to characterize two main types of thalassemia (α and β types) and healthy control blood samples. Our results suggested that the ratios of charged ions to Hb chains being at +13 would be an indicator for β-thalassemia screening.

Objective: 1q44 microdeletion syndrome is difficult to diagnose due to the wide phenotypic spectrum and strong genetic heterogeneity. We explore the correlation between the chromosome microdeletions and phenotype in a child with 1q44 microdeletion syndrome, we collected the clinical features of the patient and combined them with adjacent copy number variation (CNV) regions previously reported.Methods: We collected the full medical history of the patient and summarized her clinical symptoms. Whole-exome sequencing (WES) and CapCNV analysis were performed with DNA extracted from both the patient's and her parents' peripheral blood samples. Fluorescent quantitative PCR (q-PCR) was performed for the use of verification to the CNV regions.Results: A 28.7 KB microdeletion was detected in the 1q44 region by whole-exome sequencing and low-depth whole-genome sequencing. The deleted region included the genes COX20 and HNRNPU. As verification, karyotype analysis showed no abnormality, and the results of qPCR were consistent with that of whole-exome sequencing and CapCNV analysis.Conclusion: The patient was diagnosed with 1q44 microdeletion syndrome with clinical and genetic analysis. Analyzing both whole-exome sequencing and CapCNV analysis can not only improve the diagnostic rate of clinically suspected syndromes that present with intellectual disability (ID) and multiple malformations but also support further study of the correlation between CNVs and clinical phenotypes. This study lays the foundation for the further study of the pathogenesis of complex diseases.

Pelvic intensity-modulated radiation therapy (IMRT) combined with concurrent chemotherapy is an effective treatment for cervical cancer; however, radiation resistance impairs its clinical benefit. The vaginal microbiome plays an important but poorly understood role in cancer radiochemotherapy. In this study, we investigated the effects of treatment on the overall composition and alteration of the vaginal microbiome in patients receiving pelvic IMRT with concurrent cisplatin-based chemotherapy. We collected samples from twenty patients with cervical cancer and six healthy controls and performed 16S rRNA sequencing. Vaginal microbial composition analysis revealed significant differences between the two groups, but no significant differences between radiation treatment time points. However, the relative abundances of Gammaproteobacteria, Gemmatimonadetes, Gemmatimonadales, Pseudomonadales, Gemmatimonadaceae, Rikenellaceae, Acinetobacter, Desulfovibrio, Prevotella 9, Rikenellaceae RC9 gut group, Turicibacter, and the metagenome increased with time. The results encourage further study into the effects of the vaginal microbiome on cervical cancer treatment strategies, especially radiochemotherapy. Better understanding of these effects could inform new therapeutic approaches to enhance the efficacy of radiochemotherapy.

Stroke mostly including ischemic stroke is the second leading mortality and disability worldwide. Oxidative stress injury occurred during ischemic stroke treatment generally. A high amount of reactive oxygen species (ROS) is involved in oxidative stress induction. Transient receptor potential vanilloid 1 (TRPV1) has been shown to regulate oxidative stress and apoptosis in microglia; however, the detailed mechanisms remain unclear. We aimed to explore whether autophagy-regulated oxidative stress and apoptosis are associated with TRPV1. The model of oxygen and glucose deprivation (OGD/R) in microglia was established. The siRNA of Atg5 and inhibitors and agonists of both autophagy and TRPV1 were involved in our study. Autophagy-related markers Atg5, LC3II/LC3I, and Beclin-1 were measured, and the autophagosome was observed under a transmission electron microscope (TEM). Caspase 3 was detected using ELISA. ROS and JC-1 were detected using flow cytometry. Apoptosis was observed by TUNEL. The results indicated that oxidative stress-induced injury and apoptosis may be impeded by the increasing autophagy, and TRPV1 inhibition could suppress the OGD/R-induced autophagy of microglia. However, the effect of TRPV1’s inhibitor on oxidative stress and apoptosis was not obvious when the autophagy was blocked. These findings suggested that TRPV1 may exhibit antioxidative and antiapoptosis effect on OGD/R-induced microglia. However, the experimental results do not fully demonstrate that the TRPV1-mediated antioxidative and antiapoptosis effect is through the affecting autophagy entirely.

Various reaction mechanisms for the catalytic degradation of formaldehyde (HCHO) remain to be debated. Density functional theory (DFT) was applied to investigate whether the catalytic oxidation of HCHO on pristine Co3O4 (110) surface follows the Mars-van Krevelen (MvK) mechanism or the Langmuir–Hinshelwood (L-H) mechanism. Firstly, HCHO and O2 co-adsorb on the surface and two H atoms from HCHO are peculiarly prone to transfer to O2, forming CO and HOOH. For the MvK mechanism, CO2 is generated through CO grabbing a lattice oxygen. Meanwhile, the O–O bond of HOOH is broken into two OH groups. One OH fills the oxygen vacancy and its H atom moves to another OH group for H2O formation. For the L-H mechanism, CO directly obtains one OH group to generate COOH. Subsequently, the H atom of COOH transfers to another OH group along with CO2 and H2O generation. Both two mechanisms exhibit a similar maximum activation barrier. The lattice oxygen in the MvK mechanism and the surface-absorbed OH group in the L-H mechanism are the key reactive oxygen species. The small difference in energetic span further suggests that the catalytic cycle through the two mechanisms is feasible. This theoretical study provides new insight into the catalytic reaction path of HCHO oxidation on pristine Co3O4 surface.

Microbial infection can trigger the assembly of inflammasomes and promote secretion of cytokines, such as IL-1β and IL-18. It is well-known that Salmonella modulates the activation of NLRC4 (NLR family CARD domain-containing protein 4) and NLRP3 (NLR family pyrin domain-containing 3) inflammasomes, however the mechanisms whereby Salmonella avoids or delays inflammasome activation remain largely unknown. Therefore, we used Salmonella Enteritidis C50336ΔfliC transposon library to screen for genes involved in modulating inflammasomes activation. The screen revealed the galactose metabolism-related gene galE to be essential for inflammasome activation. Here, we found that inflammasome activation was significantly increased in J774A.1 cells or wild-type bone marrow-derived macrophages (BMDMs) during infection by ΔfliCΔgalE compared to cells infected with ΔfliC. Importantly, we found that secretion of IL-1β was Caspase-1-dependent, consistent with canonical NLRP3 inflammasome activation. Furthermore, the virulence of ΔfliCΔgalE was significantly decreased compared to ΔfliC in a mouse model. Finally, RNA-seq analysis showed that multiple signaling pathways related to the inflammasome were subject to regulation by GalE. Taken together, our results suggest that GalE plays an important role in the regulatory network of Salmonella evasion of inflammasome activation.

Salmonella enterica serovar Enteritidis (S. Enteritidis) is an important zoonotic pathogen that can lead to diarrhea and systemic infections in humans and mortality in animals. This is a major public health issue worldwide. Safe and effective vaccines are urgently needed to control and prevent Salmonella infection. Subunit vaccines are safe and provide targeted protection against Salmonella spp. Here, we developed and evaluated an S. Enteritidis subunit vaccine candidate, the rHis-SseB adjuvant with simvastatin. We amplified the SseB gene from S. Enteritidis C50041 genomic DNA and expressed the recombinant proteins rHis-SseB and rGST-SseB using the Escherichia coli system. Western blotting confirmed the immunoreactivity of recombinant proteins rHis-SseB and rGST-SseB with antisera against Salmonella Enteritidis C50041. In a mouse model of intramuscular vaccination, co-immunization with rHis-SseB and simvastatin significantly enhanced both the SseB-specific antibody titer in serum (humoral immune response) and splenic lymphocyte proliferation (cellular immune response). Co-immunization with rHis-SseB and simvastatin provided 60% protection against subsequent challenge with the S. Enteritidis C50041 strain and decreased bacterial colonization in the liver and spleen. These findings provide a basis for the development of an S. Enteritidis subunit vaccine.

Objective: Brain imaging is important in diagnosing children with cerebral palsy (CP) and in identifying its etiology. To provide study navigation in this field, a bibliometric analysis was conducted by analyzing the most highly cited articles.Methods: The Web of Science All Databases were used for literature search in this study. All original articles on imaging in children with CP were searched. Two reviewers screened the search results independently and eliminated articles based on exclusion criteria such as participants over 20 years old, topics referring to images outside of the brain, or trauma. According to descending order of yearly citation counts, the top 25% of all included articles were considered as highly cited articles. Information such as yearly citations, research purposes, imaging modalities, CP types, and study designs were recorded and analyzed.Results: A total of 50 highly cited articles ranked by yearly citations (from 23.85 to 3.33, 1991–2018) were included in this study. Considering different research purposes, these studies were classified into three categories: diagnosis studies (n = 25; 1991–2017, median: 2011), mechanism studies (n = 15; 1999–2018; median: 2014), and prognosis and therapeutic effect studies (n = 10; 2008–2017; median: 2014.5). First, for diagnosis studies, 22 studies used single modality and three used multi-modalities; the majority of these studies focused on diagnostic value evaluation (n = 10) and image performance (n = 12) of a single type of CP (n = 15) by using descriptive (n = 14) or cross-sectional approaches (n = 10). Second, for mechanism studies, the ratio between single and multi-modality was 8:7; most of these studies concentrated on a single subtype of spastic CP (hemiplegia = 10, quadriplegia = 2) with a cross-sectional study design (n = 10). Third, regarding the prognosis and therapeutic effect studies, the single vs. multi-modality ratio was 5:5, and these studies were dedicated to the efficiency of constraint-induced movement therapy in children with hemiplegia; paired design trials (n = 6) and randomized controlled trials (n = 2) were used more frequently.Conclusion: Studies using multi-modality and high-level evidence-based design to provide information regarding mechanism, prognosis, and therapeutic efficacy may be the potential future research direction in the field of CP research.

ABSTRACT Oral health and changes in the oral microbiome have been associated with both local and systemic cancer. Poor oral hygiene is a known risk factor for nasopharyngeal carcinoma (NPC), a virally associated head and neck cancer endemic to southern China. We explored the relationship between NPC and the oral microbiome using 16S rRNA sequencing in a study of 499 NPC patients and 495 population-based age and sex frequency-matched controls from an area of endemicity of Southern China. We found a significant reduction in community richness in cases compared to that in controls. Differences in the overall microbial community structure between cases and controls could not be explained by other potential confounders; disease status explained 5 times more variation in the unweighted UniFrac distance than the next most explanatory variable. In feature-based analyses, we identified a pair of coexcluding Granulicatella adiacens amplicon sequence variants (ASVs) which were strongly associated with NPC status and differed by a single nucleotide. The G. adiacens variant an individual carried was also associated with the overall microbial community based on beta diversity. Co-occurrence analysis suggested the two G. adiacens ASVs sit at the center of two coexcluding clusters of closely related organisms. Our results suggest there are differences in the oral microbiomes between NPC patients and healthy controls, and these may be associated with both a loss of microbial diversity and niche specialization among closely related commensals. IMPORTANCE The relationship between oral health and the risk of nasopharyngeal carcinoma (NPC) was previously established. However, the role of oral microbiome has not been evaluated in the disease in a large epidemiological study. This paper clearly establishes a difference in the oral microbiomes between NPC patients and healthy controls which cannot be explained by other confounding factors. It furthermore identifies a pair of closely related coexcluding organisms associated with the disease, highlighting the importance of modern methods for single-nucleotide resolution in 16S rRNA sequence characterization. To the best of our knowledge, this is one of the first examples of cancer-associated niche specialization of the oral microbiome.

Abstract Discriminating depressive episodes of bipolar disorder (BD) from major depressive disorder (MDD) is a major clinical challenge. Recently, gut microbiome alterations are implicated in these two mood disorders; however, little is known about the shared and distinct microbial characteristics in MDD versus BD. Here, using 16S ribosomal RNA (rRNA) gene sequencing, the microbial compositions of 165 subjects with MDD are compared with 217 BD, and 217 healthy controls (HCs). It is found that the microbial compositions are different between the three groups. Compared to HCs, MDD is characterized by altered covarying operational taxonomic units (OTUs) assigned to the Bacteroidaceae family, and BD shows disturbed covarying OTUs belonging to Lachnospiraceae, Prevotellaceae, and Ruminococcaceae families. Furthermore, a signature of 26 OTUs is identified that can distinguish patients with MDD from those with BD or HCs, with area under the curve (AUC) values ranging from 0.961 to 0.986 in discovery sets, and 0.702 to 0.741 in validation sets. Moreover, 4 of 26 microbial markers correlate with disease severity in MDD or BD. Together, distinct gut microbial compositions are identified in MDD compared to BD and HCs, and a novel marker panel is provided for distinguishing MDD from BD based on gut microbiome signatures.

Background The protective effects of polyamines on cardiovascular disease have been demonstrated in many studies. However, the roles of spermidine, a natural polyamine, in abdominal aortic aneurysm (AAA) disease have not been studied. In this study, we investigated the influence and potential mechanisms of spermidine treatment on experimental AAA disease. Methods and Results Experimental AAAs were induced in 8‐ to 10‐week‐old male C57BL/6J mice by transient intra‐aortic infusion of porcine pancreatic elastase. Spermidine was administered via drinking water at a concentration of 3 mmol/L. Spermidine treatment prevented experimental AAA formation with preservation of medial elastin and smooth muscle cells. In immunostaining, macrophages, T cells, neutrophils, and neovessels were significantly reduced in aorta of spermidine‐treated, as compared with vehicle‐treated elastase‐infused mice. Additionally, flow cytometric analysis showed that spermidine treatment reduced aortic leukocyte infiltration and circulating inflammatory cells. Furthermore, we demonstrated that spermidine treatment promoted autophagy‐related proteins in experimental AAAs using Western blot analysis, immunostaining, and transmission electron microscopic examination. Autophagic function was evaluated for human abdominal aneurysmal and nonaneurysmal adjacent aortae from AAA patients using Western blot analysis and immunohistochemistry. Dysregulated autophagic function, as evidenced by increased SQSTM1/p62 protein and phosphorylated mTOR, was found in aneurysmal, as compared with nonaneurysmal, aortic segments. Conclusions Our results suggest that spermidine supplementation limits experimental AAA formation associated with preserved aortic structural integrity, attenuated aortic inflammatory infiltration, reduced circulating inflammatory monocytes, and increased autophagy‐related proteins. These findings suggest that spermidine may be a promising treatment for AAA disease.

Acute ischemic stroke (AIS) is common in patients with cancer, and mounting clinical evidence suggests that it may shorten the survival of cancer patients. But how stroke affects the progression of cancer remains unclear. We inoculated B16 tumor cells (2 × 105) subcutaneously before distal middle cerebral artery occlusion (dMCAO) or sham surgery in C57BL/6 mice and found that compared to sham operated mice, dMCAO mice developed significantly increased tumor volume and were accompanied by lower survival rate. To explore the underlying mechanism, we performed RNA-sequencing analysis of the tumor tissue from mice with or without stroke and found prominent upregulation of lipocalin 2 (LCN2) in the tumor from stroke mice compared to those from sham mice. Using quantitative reverse transcription-PCR, we confirmed increased mRNA expression of LCN2 as well as anti-inflammatory cytokines-Arg1, IL-10, and decreased mRNA level of pro-inflammatory cytokines-IL-6, IL-23 in the tumor of cancer-bearing stroke mice. Both immunofluorescence staining and flow cytometry analysis revealed that increased expression of LCN2 was mainly derived from the polymorphonuclear myeloid derived suppressor cells (PMN-MDSCs) in the tumor. We also found that stroke reduced the PMN-MDSCs in the peripheral blood, but increased PMN-MDSCs in the tumor of the cancer-bearing mice after stroke. In conclusion, cerebral ischemic stroke may exacerbate cancer progression by increasing LCN2 expression in PMN-MDSCs, which turns out to be a promising therapeutic target to suppress cancer progression after ischemic stroke.

Abstract Background The increase in the levels of reactive oxygen species (ROS) in acute myeloid leukemia (AML) patients has been previously described; thus, it is important to regulate ROS levels in AML. Methods Flow cytometry were used to assess the in vitro effect of compound kushen injection (CKI). Quantitative proteomics were used to analyse the mechanism. The AML patient-derived xenograft (PDX) model were used to evaluate the in vivo effect of CKI. Results We found that intracellular ROS levels in AML cells were decreased, the antioxidant capacity were increased when treated with CKI. CKI inhibited the proliferation of AML cells and enhanced the cytotoxicity of AML cells, which has few toxic effects on haematopoietic stem cells (HSCs) and T cells. At the single-cell level, individual AML cells died gradually by CKI treatment on optofluidic chips. CKI promoted apoptosis and arrested cell cycle at G1/G0 phase in U937 cells. Furthermore, higher peroxiredoxin-3 (Prdx3) expression levels were identified in CKI-treated U937 cells through quantitative proteomics detection. Mechanically, the expression of Prdx3 and peroxiredoxin-2 (Prdx2) was up-regulated in CKI-treated AML cells, while thioredoxin 1 (Trx1) was reduced. Laser confocal microscopy showed that the proteins Prdx2 could be Interacted with Trx1 by CKI treatment. In vivo, the survival was longer and the disease was partially alleviated by decreased CD45+ immunophenotyping in peripheral blood in the CKI-treated group in the AML PDX model. Conclusions Antioxidant CKI possess better clinical application against AML through the Prdxs/ROS/Trx1 signalling pathway.

Background/Aims: Fibroblast growth factor receptor 2 (FGFR2) has attracted considerable interest as a therapeutic target in gastric cancer (GC). There is growing evidence to suggest that the bioavailability of the potent pro-tumor function of FGFR2 is associated with thrombospondins (TSPs). As a follow-on from our previous study, here we evaluated the potential clinical significance and mechanism of the relationship between FGFR2 and TSP4 in GC. Methods: Expression levels of FGFR2 and TSP4 were detected by immunohistochemistry in GC tissue microarray slides. SGC7901 and MKN28 cell lines were used to confirm the relationship between FGFR2 and TSP4. In vitro cell viability, colony formation, and invasion and migration assays were performed to evaluate the effect of FGFR2-TSP4 axis on tumor cell activities. The mechanism of TSP4 regulated by FGFG2 was explored via small molecular inhibitors in vitro and a xenograft model. Results: FGFR2 was shown to be markedly overexpressed in GC tissues and was correlated with a high risk of lymph node metastasis, late clinical stage, and poor prognosis. Low TSP4 expression was associated with shorter overall survival (OS) and advanced stage in GC patients. Interestingly, correlation analysis indicated that FGFR2 was negatively associated with TSP4. Indeed, in vitro and in vivo experiments suggested FGFR2 activation could downregulate TSP4 expression, which played an important role in the proliferation, invasion and migration of GC cells. We also found involvement of the PI3K-AKT-mTOR pathway in the FGFR2-TSP4 axis. Conclusion: The FGFR2 signal promotes human GC progression through the downregulation of TSP4 via PI3K-AKT-mTOR pathway. Our findings provide a foundation for further investigating promising therapeutic strategies for GC overexpressing FGFR2.

Abstract Members in Motin family, or Angiomotins (AMOTs), are adaptor proteins that localize in the membranous, cytoplasmic or nuclear fraction in a cell context-dependent manner. They control the bioprocesses such as migration, tight junction formation, cell polarity, and angiogenesis. Emerging evidences have demonstrated that AMOTs participate in cancer initiation and progression. Many of the previous studies have focused on the involvement of AMOTs in Hippo-YAP1 pathway. However, it has been controversial for years that AMOTs serve as either positive or negative growth regulators in different cancer types because of the various cellular origins. The molecular mechanisms of these opposite roles of AMOTs remain elusive. This review comprehensively summarized how AMOTs function physiologically and how their dysregulation promotes or inhibits tumorigenesis. Better understanding the functional roles of AMOTs in cancers may lead to an improvement of clinical interventions as well as development of novel therapeutic strategies for cancer patients.

Abstract Background Subjects with elevated Epstein-Barr virus (EBV) immunoglobulin A (IgA) titers have a higher risk of developing nasopharyngeal carcinoma (NPC), indicating that reactivation of EBV in the local mucosa might be important for NPC carcinogenesis. Cigarette smoking appears to be one of the environmental risk factors for NPC. However, it remains unclear whether smoking-induced nasopharyngeal carcinogenesis acts through reactivating EBV in the nasopharyngeal mucosa. Therefore, this study aims to investigate the association between cigarette smoking and nasopharyngeal EBV reactivation in a NPC high-risk population. Methods A NPC high-risk cohort study, established from a population-based NPC screening program of 22,816 subjects, consisted of 1045 subjects with elevated serum IgA antibodies against EBV viral capsid antigen (VCA/IgA). Among high-risk subjects, information on detailed cigarette smoking history was collected among 313 male subjects. The associations between cigarette smoking and EBV antibody levels, EBV DNA load of the nasopharynx were analyzed. Results No significant association was observed between either nasopharyngeal EBV DNA load or serum VCA/IgA titers and smoking status, age at smoking initiation, daily smoking intensity, smoking duration, cigarette type, or pack-years of smoking. Cigarette smoking characteristics in all subgroups did not correlate with nasopharyngeal EBV DNA positivity or EBV VCA/IgA seropositivity. Conclusions In a population at high risk of NPC, our study suggests that cigarette smoking is neither associated with nasopharyngeal EBV DNA load nor serum VCA/IgA antibody level. Smoking-associated NPC carcinogenesis may act through other mechanisms than reactivating nasopharyngeal EBV replication.

Cyber physical systems (CPSs) are rapidly developing, with increasing scale, complexity and heterogeneity. However, testing CPSs systematically to ensure that they operate with high reliability remains a big challenge. Therefore, it is necessary to summarize existing works and technologies systematically, with the aim of inspiring new inventions for more efficient CPS testing. Accordingly, this paper first investigated the advances in CPS testing methods from ten aspects, including different testing paradigms, technologies, and some non-functional testing methods (including security testing, robust testing, and fragility testing). Then, we further elaborate on the infrastructures of CPS testbeds from the perspectives of their architecture and the corresponding function analyses. Finally, challenges and future research directions are identified and discussed. It can be concluded that future CPS testing should focus more on the combination of different paradigms and technologies for multi-objective by integrating more emerging cutting-edge technologies such as Internet of things, big data, cloud computing and AI.

Continuous observations from geostationary satellites can show the morphology of precipitation cloud systems in quasi-real-time, but there are still large deviations in the inversion of precipitation. We used binary-connected area recognition technology to identify meso-β-scale rain clusters over Hainan Island from 1 June 2000 to 31 December 2018, based on Global Precipitation Measurement (GPM) Integrated Multi-satellitE Retrievals for GPM data. We defined and statistically analyzed the parameters of rain clusters to reveal the typical morphological and precipitation characteristics of rain clusters, and to explore the relationship between the parameters and rainfall intensity of rain clusters. We found that the area and long axis of rain clusters over land were larger than those over the ocean, and that continental rain clusters were usually square in shape. Rain clusters with a larger area and longer axis were concentrated on the northern side of the mountains on Hainan Island and the intensity of rain was larger on the northern and eastern sides of the mountains. The variation of continental rain clusters over time was more dramatic than the variation of oceanic clusters. The area and long axis of rain clusters was larger between 14:00 and 21:00 from April to September and the long axis of the oceanic rain clusters increased in winter. There were clear positive correlations between the area, long axis and shape of the rain clusters and the maximum rain rate. The area and long axis of continental rain clusters had a higher correlation with the rain rate than those of oceanic clusters. The establishment of a relationship between the morphology of rain clusters and precipitation helps us to understand the laws of precipitation and improve the prediction of precipitation in this region.

Abstract Background The present study compared the effects of soybean meal fermented by three different probiotics organisms with non-fermented soybean meal on growth performance, serum parameters, immune chemistry and intestinal morphology in weaned piglets. Methods One hundred and forty-four 35-day old crossbred (Duroc × Landrace × Yorkshire) piglets were randomly allocated into four different dietary treatments (n = 36 per group) containing 0, 5, 10 and 15% fermented soybean meal. Results The piglets fed fermented soybean meal showed an increase (p

Abstract Background Gastric cancer (GC) is one of the frequent causes of cancer-related death in eastern Asian population. IGF2BP2 lists in the top rank up-regulated genes in GC, but its functional role is unclear. Method The expression of IGF2BP3 in GC cell lines and primary samples was examined by qRT-PCR and Western blot. The biological role of IGF2BP3 was revealed by a series of functional in vitro studies. Its regulation by microRNAs (miRNAs) was predicted by TargetScan and confirmed by luciferase assays and rescue experiments. Results IGF2BP3 ranked the No.1 of the up-regulated genes by expression microarray analysis in GC cell lines. The expression level of IGF2BP3 was observed in GC tissues comparing with non-tumorous gastric epitheliums. The up-regulated IGF2BP3 expression was associated with poor disease specific survival. IGF2BP3 knockdown significantly inhibited cell proliferation and invasion. Apart from copy number gain, IGF2BP3 has been confirmed to be negatively regulated by tumor-suppressive miRNA, namely miR-34a. The expression of miR-34a showed negative correlation with IGF2BP3 mRNA expression in primary GC samples and more importantly, re-overexpression of IGF2BP3 rescued the inhibitory effect of miR-34a. Conclusion We compressively revealed the oncogenic role of IGF2BP3 in gastric tumorigenesis and confirmed its activation is partly due to the silence of miR-34a. Our findings identified useful prognostic biomarker and provided clinical translational potential.

An improved multi-carrier M-ary differential chaos shift keying (MM-DCSK) system is presented, where differential modulation and demodulation are carried out across multiple carriers in the frequency domain, so channel estimation is not needed. For one data frame transmission, only one noninformation-bearing reference sub-carrier signal is required, and the reference of each information-bearing sub-carrier is its previous sub-carrier signal, thus high energy efficiency is attained. If channel response changes during a frame period, the time diversity is achieved. In addition, the peak-to-average power ratio (PAPR) is considered, and it is found that adjacent symbols with a large Euclidean distance achieve a low PAPR. Accordingly, a low-complexity PAPR reduction algorithm is proposed based on symbol-interleaving with only one inverse fast Fourier transform processor. The simulation results demonstrate that the system with the proposed algorithm dramatically reduces the PAPR. Analytical bit-error-rate expressions are derived and verified by simulations over additive white Gaussian noise and multi-path fading channels.

The mechanism of bipolar disorder is unclear. Growing evidence indicates that gut microbiota plays a pivotal role in mental disorders. This study aimed to find out changes in the gut microbiota in bipolar depression (BD) subjects following treatment with quetiapine and evaluate their correlations with the brain and immune function. Totally 36 subjects with BD and 27 healthy controls (HCs) were recruited. The severity of depression was evaluated with the Montgomery-Asberg depression rating scale (MADRS). At baseline, fecal samples were collected and analyzed by quantitative polymerase chain reaction (qPCR). T lymphocyte subsets were measured to examine immune function. Near-infrared spectroscopy (NIRS) was used to assess brain function. All BD subjects received quetiapine treatment (300 mg/d) for four weeks, following which the fecal microbiota and immune profiles were reexamined. Here, we first put forward the new concept of brain-gut coefficient of balance (B-GCB), which referred to the ratio of [oxygenated hemoglobin]/(Bifidobacteria to Enterobacteriaceae ratio), to analyze the linkage between the gut microbiota and brain function. At baseline, the CD3+ T cell proportion was positively correlated with log10 Enterobacter spp count, whereas the correlativity between the other bacteria and immune profiles were negative. Log10 B-GCB was positively correlated with CD3+ T cell proportion. In subjects with BD, counts of Faecalibacterium prausnitzii, Bacteroides–Prevotella group, Atopobium Cluster, Enterobacter spp, and Clostridium Cluster IV were higher, whereas the log10 (B/E) were lower than HCs (B/E refers to Bifidobacteria to Enterobacteriaceae ratio and represents microbial colonization resistance). After treatment, MADRS scores were reduced, whereas the levels of Eubacterium rectale, Bifidobacteria, and B/E increased. The composition of the gut microbiota and its relationship to brain function were altered in BD subjects. Quetiapine treatment was effective for depression and influenced the composition of gut microbiota in patients.Clinical Trial Registration:http://www.chictr.org.cn/index.aspx, identifier ChiCTR-COC-17011401, URL: http://www.chictr.org.cn/listbycreater.aspx.

Progressive neurological deterioration poses enormous burden on the aging population with ischemic stroke and neurodegenerative disease patients, such as Alzheimers’ disease and Parkinson’s disease. The past two decades have witnessed remarkable advances in the research of neurovascular unit dysfunction, which is emerging as an important pathological feature that underlies these neurological disorders. Dysfunction of the unit allows penetration of blood-derived toxic proteins or leukocytes into the brain and contributes to white matter injury, disturbed neurovascular coupling and neuroinflammation, which all eventually lead to cognitive dysfunction. Recent evidences suggest that aging-related oxidative stress, accumulated DNA damage and impaired DNA repair capacities compromises the genome integrity not only in neurons, but also in other cell types of the neurovascular unit, such as endothelial cells, astrocytes and pericytes. Combating DNA damage or enhancing DNA repair capacities in the neurovascular unit represents a promising therapeutic strategy for vascular and neurodegenerative disorders. In this review, we focus on aging related mechanisms that underlie DNA damage and repair in the neurovascular unit and introduce several novel strategies that target the genome integrity in the neurovascular unit to combat the vascular and neurodegenerative disorders in the aging brain.

Neurological deficits and cognitive dysfunctions caused by acute ischemic stroke pose enormous burden to the stroke families and the communities. Restoration of the normal function of the neurovascular unit following ischemic stroke is critical for improving neurological recovery and cognitive functions after stroke. Recent evidence suggests that the myeloid cells including both the resident microglia and infiltrating monocytes/macrophages and neutrophils are highly plastic in response to the environmental cues. They intimately interact with multiple components of the neurovascular unit in response to the alarmins, danger associated pattern molecules (DAMPs) and other signals released from the ischemic brain. The aim of this review is to discuss the reciprocal interactions between the myeloid cells and the ischemic neurovascular unit during the late repair phase of cerebral ischemic stroke. We also summarize potential immunotherapeutic targets on myeloid cells and new therapeutic approaches targeting myeloid cells, such as cell transplantation, mitochondrial dynamic and extracellular vesicles-based therapy et al to enhance neurovascular repair for better stroke recovery.

Abstract This study aims to characterize the gut microbiota in depressed patients with bipolar disorder (BD) compared with healthy controls (HCs), to examine the effects of quetiapine treatment on the microbiota, and to explore the potential of microbiota as a biomarker for BD diagnosis and treatment outcome. Analysis of 16S‐ribosomal RNA gene sequences reveals that gut microbial composition and diversity are significantly different between BD patients and HCs. Phylum Bacteroidetes and Firmicutes are the predominant bacterial communities in BD patients and HCs, respectively. Lower levels of butyrate‐producing bacteria are observed in untreated patients. Microbial composition changes following quetiapine treatment in BD patients. Notably, 30 microbial markers are identified on a random forest model and achieve an area under the curve (AUC) of 0.81 between untreated patients and HCs. Ten microbial markers are identified with the AUC of 0.93 between responder and nonresponder patients. This study characterizes the gut microbiota in BD and is the first to evaluate microbial changes following quetiapine monotherapy. Gut microbiota‐based biomarkers may be helpful in BD diagnosis and predicting treatment outcome, which need further validations.

Background Citrus huanglongbing (HLB) is a destructive disease of citrus and a major threat to the citrus industry around the world. This disease accounts for substantial economic losses in China every year. Diaphorina citri Kuwayama is one of the major vectors by which citrus HLB is spread under natural conditions in China. Research is needed to identify the geographic distribution of D. citri and its major areas of occurrence and to formulate measures for early warning, monitoring, and control of this pest and citrus HLB. Methods In this study, the ecological niche modelling software MaxEnt (maximum entropy model) was combined with ArcGIS (a geographic information system) to predict the potential geographic distribution of D. citri in China. Key environmental factors and the appropriate ranges of their values were also investigated. Results Our results show that the training data provided a good forecast (AUCmean = 0.988). The highly suitable areas for D. citri in China are mainly concentrated to the south of the Yangtze River, and the total area is 139.83 × 104 km2. The area of the moderately suitable areas is 27.71 × 104 km2, with a narrower distribution than that of the highly suitable area. The important environmental factors affecting the distribution of D. citri were min temperature of coldest month, mean temperature of coldest quarter, precipitation of wettest quarter, mean temperature of warmest quarter, precipitation of warmest quarter, max temperature of warmest month, and temperature seasonality. These results provide a valuable theoretical basis for risk assessments and control of D. citri. Discussion The predicted results showed that there were highly suitable areas for D. citri in Chongqing, Hubei, Anhui, and Jiangsu. Therefore, the possibility exists for the further spread of D. citri in China in the future. Extreme temperature variables, especially the min temperature of the coldest month, play an important role in the distribution of D. citri and are most closely related to the distribution of D. citri.

Testicular structural and functional impairment is a serious complication in male diabetes mellitus (DM) patients that leads to impaired fertility in adulthood. In contrast to other endocrine therapies, islet transplantation (IT) can effectively prevent and even reverse diabetic nephropathy and myocardial damage. However, whether IT can alleviate diabetes-induced testicular injury remains unclear. In this study, we sought to investigate the effect of IT on diabetes-induced testicular damage. A diabetic rat model was established by streptozotocin injection. DM, IT, and insulin treatment (INS) groups were compared after 4 weeks of respective treatment. We confirmed that IT could effectively attenuate diabetes-induced testicular damage and recover sperm counts more extensively compared with INS in diabetic rats. In addition, significantly higher levels of superoxide dismutase (SOD) activity and lower contents of malondialdehyde (MDA) were detected in the testes of the IT group versus diabetic rats. Mechanism studies revealed that IT significantly activates the expression of Nrf-2, HO-1, and NQO-1 and inhibits upregulation of the NF-κB expression in response to DM, while INS only exhibit slight impact on the protein expression. Therefore, we speculate that IT may prevent the progression of testicular damage by downregulating oxidative stress and inhibiting inflammation via Nrf-2/HO-1 and NF-κB pathways.

The research was studying the chromium precipitation in faucets which were extracted at ambient temperature of 20 ºC, 40 ºC and 60 ºC by extraction solution, the results showed that in general, the chromium extraction in the faucets increased as the temperature rises. And the chromium extraction in different batches and different samples in the same batch varied greatly, mainly affected by materials and the processing technology. After further analysis, the detection showed that Cr VI in chromium precipitation was between 83% and 103% of the total chromium content. This indicated that Cr VI was the main form of chromium in extraction solution, which will be harmful to human health.

Naphthoquinone-based meroterpenoids are hybrid polyketide-terpenoid natural products with chemical diversity and a broad range of biological activities. Here, we report the isolation of a group of naphthoquinone-containing compounds from Streptomyces sp. B9173, and their structures were elucidated by using a combination of spectroscopic techniques, including 1D, 2D NMR, and high-resolution mass (HRMS) analysis. Seven flaviogeranin congeners or intermediates, three of which were new, have been derived from common naphthoquinone backbone and subsequent oxidation, methylation, prenylation, and amino group incorporation. Both flaviogeranin B1 (1) and B (2) contain an amino group which was incorporated into the C8 of 1,3,6,8-terhydroxynaphthalene (THN). Flaviogeranin D (3) contains an intact C-geranylgeranyl residue attached to the C2 of THN, while the O-geranylgeranyl group of 2 links with the hydroxyl on the C2 site of THN. Four compounds were selected and tested for antibacterial activity and cytotoxicity, with 3 and flaviogeranin C2 (5) displaying potent activity against selected bacteria and cancer cell lines. In light of the structure features of isolated compounds and the biosynthetic genes, a biosynthetic pathway of naphthoquinone-based flaviogeranins has been proposed. These isolated compounds not only extend the structural diversity but also represent new insights into the biosynthesis of naphthoquinone-based meroterpenoids.

Opioid analgesics such as morphine have indispensable roles in analgesia. However, morphine use can elicit side effects such as respiratory depression and constipation. It has been reported that G protein-biased agonists as substitutes for classic opioid agonists can alleviate (or even eliminate) these side effects. The compounds PZM21 and TRV130 could be such alternatives. Nevertheless, there are controversies regarding the efficacy and G protein-biased ability of PZM21. To demonstrate a rationale for the reduced biasing agonism of PZM21 compared with that of TRV130 at the molecular level, we undertook a long-term molecular dynamics simulation of the μ-opioid receptor (MOR) upon the binding of three ligands: morphine, TRV130, and PZM21. We found that the delayed movement of the W2936.48 (Ballesteros–Weinstein numbering) side chain was a factor determining the dose-dependent agonism of PZM21. Differences in conformational changes of W3187.35, Y3267.43, and Y3367.53 in PZM21 and TRV130 explained the observed differences in bias between these ligands. The extent of water movements across the receptor channel was correlated with analgesic effects. Taken together, these data suggest that the observed differences in conformational changes of the studied MOR–ligand complexes point to the low-potency and lower bias effects of PZM21 compared with the other two ligands, and they lay the foundation for the development of G protein-biased agonists.

The Lattice Boltzmann method (LBM) has been applied for the simulation of lid-driven flows inside cavities with internal two-dimensional circular obstacles of various diameters under Reynolds numbers ranging from 100 to 5000. With the LBM, a simplified square cross-sectional cavity was used and a single relaxation time model was employed to simulate complex fluid flow around the obstacles inside the cavity. In order to made better convergence, well-posed boundary conditions should be defined in the domain, such as no-slip conditions on the side and bottom solid-wall surfaces as well as the surface of obstacles and uniform horizontal velocity at the top of the cavity. This study focused on the flow inside a square cavity with internal obstacles with the objective of observing the effect of the Reynolds number and size of the internal obstacles on the flow characteristics and primary/secondary vortex formation. The current LBM has been successfully used to precisely simulate and visualize the primary and secondary vortices inside the cavity. In order to validate the results of this study, the results were compared with existing data. In the case of a cavity without any obstacles, as the Reynolds number increases, the primary vortices move toward the center of the cavity, and the secondary vortices at the bottom corners increase in size. In the case of the cavity with internal obstacles, as the Reynolds number increases, the secondary vortices close to the internal obstacle become smaller owing to the strong primary vortices. In contrast, depending on the sizes of the obstacles ( R / L = 1/16, 1/6, 1/4, and 2/5), secondary vortices are induced at each corner of the cavity and remain stationary, but the secondary vortices close to the top of the obstacle become larger as the size of the obstacle increases.

This paper presents a multi-state adaptive early warning method for mechanical equipment and proposes an adaptive dynamic update model of the equipment alarm threshold based on a similar proportion and state probability model. Based on the similarity of historical equipment, the initial thresholds of different health states of equipment can be determined. The equipment status is divided into four categories and analyzed, which can better represent its status and provide more detailed and reasonable guidance. The obtained dynamic alarm lines at all levels can regulate the operation range of equipment in the different health states. Compared to the traditional method of a fixed threshold, this method can effectively reduce the number of false alarms and attains a higher prediction accuracy, which demonstrates its effectiveness and superiority. Finally, the method was verified by means of lifetime data of a rolling bearings. The results show that the model improves the timely detection of the abnormal state of the equipment, greatly reduces the false alarm rate, and even overcomes the limitation of independence between the fixed threshold method and equipment state. Moreover, multi-state division can accurately diagnose the current equipment state, which should be considered in maintenance decision-making.

Differential evolution (DE) algorithms for software testing usually exhibited limited performance and stability owing to possible premature-convergence-related aging during evolution processes. This paper proposes a new framework comprising an antiaging mechanism, that is, a rebirth strategy with partial memory against aging, for the existing DE algorithm and a specialized fitness function. The results of application of the proposed framework to instantiate three DE algorithms with different mutation schemas indicate that it significantly improved their effectiveness, performance, and stability.

Necroptosis is the best-described form of regulated necrosis at present, which is widely recognized as a component of caspase-independent cell death mediated by the concerted action of receptor-interacting protein kinase 1 (RIPK1) and receptor-interacting protein kinase 3 (RIPK3). Mixed-lineage kinase domain-like (MLKL) was phosphorylated by RIPK3 at the threonine 357 and serine 358 residues and then formed tetramers and translocated onto the plasma membrane, which destabilizes plasma membrane integrity leading to cell swelling and membrane rupture. Necroptosis is downstream of the tumor necrosis factor (TNF) receptor family, and also interaction with NOD-like receptor pyrin 3 (NLRP3) induced inflammasome activation. Multiple inhibitors of RIPK1 and MLKL have been developed to block the cascade of signal pathways for procedural necrosis and represent potential leads for drug development. In this review, we highlight recent progress in the study of roles for necroptosis in cerebral ischemic disease and discuss how these modifications delicately control necroptosis.

Accurate traffic sensor data is essential for traffic operation management systems and acquisition of real-time traffic surveillance data depends heavily on the reliability of the traffic sensors (e.g., wide range detector, automatic traffic recorder). Therefore, detecting the health status of the sensors in a traffic sensor network is critical for the departments of transportation as well as other public and private entities, especially in the circumstances where real-time decision is required. With the purpose of efficiently determining the sensor health status and identifying the failed sensor(s) in a timely manner, this paper proposes a graphical modeling approach called spatiotemporal pattern network (STPN). Traffic speed and volume measurement sensors are used in this paper to formulate and analyze the proposed sensor health monitoring system and historical time-series data from a network of traffic sensors on the Interstate 35 (I-35) within the state of Iowa is used for validation. Based on the validation results, we demonstrate that the proposed approach can: (i) extract spatiotemporal dependencies among the different sensors which leads to an efficient graphical representation of the sensor network in the information space, and (ii) distinguish and quantify a sensor issue by leveraging the extracted spatiotemporal relationship of the candidate sensor(s) to the other sensors in the network.

Traffic dynamics in the urban interstate system are critical in terms of highway safety and mobility. This paper proposes a systematic data mining technique to detect traffic system-level anomalies in a batch-processing fashion. Built on the concepts of symbolic dynamics, a spatiotemporal pattern network (STPN) architecture is developed to capture the system characteristics. This novel spatiotemporal graphical modeling approach is shown to be able to extract salient time series features and discover spatial and temporal patterns for a traffic system. An information-theoretic metric is used to quantify the causal relationships between sub-systems. By comparing the structural similarity of the information-theoretic metrics of the STPNs learnt from each day, a day with anomalous system characteristics can be identified. A case study is conducted on an urban interstate in Iowa, USA, with 11 roadside radar sensors collecting 20-second resolution speed and volume data. After applying the proposed methods on one-month data (Feb. 2017), several system-level anomalies are detected. The potential causes that include inclement weather condition and non-recurring congestion are also verified to demonstrate the efficacies of the proposed technique. Compared to the traditional predefined performance measures for the traffic systems, the proposed framework has advantages in capturing spatiotemporal features in a fast and scalable manner.

Speed-volume-density relationship and capacity are key elements in modelling traffic operations, designing roadways, and evaluating facility performance. This paper uses a modified five-parameter logistic model to describe the speed-density relationship. The calibrated speed-density models show that the stop-and-go speed (Vb) and shape parameters (θ1 and θ2) are similar for work zones and the nonwork zone site. Accordingly, an operational capacity prediction method is proposed. To demonstrate the effectiveness of the proposed method, the predicted operational capacities are compared with the field data, Highway Capacity Manual method, the output of WorkZoneQ software, and the ensemble tree approach under different work zone scenarios. Furthermore, a lifetime distribution prediction framework for stochastic capacity of work zones is proposed. The predicted lifetime distribution can well capture the tendency of the observed work zone capacities.

Hepatitis B virus (HBV)-associated acute-on-chronic liver failure (HBV-ACLF), characterized by an acute deterioration of liver function in the patients with chronic hepatitis B (CHB), is lack of predicting biomarkers for prognosis. Plasma is an ideal sample for biomarker discovery due to inexpensive and minimally invasive sampling and good reproducibility. In this study, immuno-depletion of high-abundance plasma proteins followed by iTRAQ-based quantitative proteomic approach was employed to analyze plasma samples from 20 healthy control people, 20 CHB patients and 20 HBV-ACLF patients, respectively. As a result, a total of 427 proteins were identified from these samples, and 42 proteins were differentially expressed in HBV-ACLF patients as compared to both CHB patients and healthy controls. According to bioinformatics analysis results, 6 proteins related to immune response (MMR), inflammatory response (OPN, HPX), blood coagulation (ATIII) and lipid metabolism (APO-CII, GP73) were selected as biomarker candidates. Further ELISA analysis confirmed the significant up-regulation of GP73, MMR, OPN and down-regulation of ATIII, HPX, APO-CII in HBV-ACLF plasma samples (p < 0.01). Moreover, receiver operating characteristic (ROC) curve analysis revealed high diagnostic value of these candidates in assessing HBV-ACLF. In conclusion, present quantitative proteomic study identified 6 novel HBV-ACLF biomarker candidates and might provide fundamental information for development of HBV-ACLF biomarker.