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Acupuncture is a traditional Chinese medicine treatment that has widely been used to modulate gastrointestinal dysfunction caused by irritable bowel syndrome (IBS) and to alleviate the resulting pain. Recent studies have shown that gastrointestinal dysfunction caused by IBS is associated with dysregulation of the brain's central and peripheral nervous system, while functional magnetic resonance imaging (fMRI) helps explore functional abnormality of the brain. However, previous studies rarely used fMRI to study the correlations between brain functional connection, interaction, or segregation (e.g., network degree and clustering coefficient) and acupuncture stimulation in IBS. To bridge this knowledge gap, we study the changed brain functional connection, interaction, and segregation before and after acupuncture stimulation for diarrhea-dominant IBS (IBS-D) with the help of complex network methods based on fMRI. Our results indicate that the abnormal functional connections (FCs) in the right hippocampus, right superior occipital gyrus, left lingual gyrus, left middle occipital gyrus, and the cerebellum, and abnormal network degree in right middle occipital gyrus, where normal controls are significantly different from IBS-D patients, are improved after acupuncture stimulation. These changed FCs and the network degree before and after acupuncture stimulation have significant correlations with the changed clinical information including IBS symptom severity score (r = −0.54, p = 0.0065) and IBS quality of life (r = 0.426, p = 0.038). We conclude that the changes of the brain functional connection, interaction, and segregation in the hippocampus, middle and superior occipital gyrus, cerebellum, and the lingual gyrus may be related to acupuncture stimulation. The abnormal functional connection, interaction, and segregation in IBS-D may be improved after acupuncture stimulation.

The C-eigenpair of piezoelectric tensors finds applications in the area of the piezoelectric effect and converse piezoelectric effect. In this paper, we provide some characterizations of C-eigenvectors by exploring the structure of piezoelectric tensors, and establish sharp C-eigenvalue inclusion intervals via Cauchy–Schwartz inequality. Further, we propose the lower and upper bounds of the largest C-eigenvalue and evaluate the efficiency of the best rank-one approximation of piezoelectric tensors. Numerical examples are proposed to verify the efficiency of the obtained results.

The current study was designed to investigate the chemical composition, amino acid content, and rumen degradation characteristics (nylon bag method) of six organic feeds to illustrate their feeding values. The feeds analyzed were: corn grain (CG), soybean cake (SC), wheat bran (WB), corn silage (CS), oat hay (OT), and alfalfa hay (AF). Our results showed that the contents of crude protein (CP) (47.46%) and ether extract (EE) (8.23%) in SC were highest. The contents of neutral detergent fiber (NDF) (65.00%) and acid detergent fiber (ADF) (39.16%) in OT were highest. The contents of total amino acid (TAA) (42.95%) and essential amino acid (EAA) (19.73%) in SC were highest. Among SC, WB, and CG, the effective degradation rate (ED) of dry matter (DM) is SC (87.89%) > WB (73.32%) > CG (64.25%); the ED value of CP is CG (82.37%) > WB (82.40%) > SC (60.47%). Among CS, OT, and AF, the effective degradation rate (ED) of DM is CS (72.68%) > OT (59.97%) > AF (58.89%); the ED value of CP is AF (76.46%) > CS (72.03%) > OT (71.99%). In conclusion, the chemical composition, amino acid content, and rumen degradation rate of SC and AF were better than those of the other four feeds.

Metformin is a widely prescribed anti-diabetes drug with potential utilities for cancer therapies. Several studies have related metformin to the reduced risk of cholangiocarcinoma (CCA), highlighting its potentialities for the treatments of CCA. However, the underlying molecular mechanisms remain elusive. Here, we demonstrated that metformin treatment could inhibit proliferations of the human CCA cell lines Mz-ChA-1 and QBC939 in dose-dependent manners. The NMR-based metabonomic analyses showed distinct discriminations between the metformin-treated (Met) and control (Ctrl) groups of both CCA cells. Characteristic metabolites were identified by a combination of multivariate statistical analysis of 1D 1H-NMR spectral data and the pair-wise t-test of metabolite levels. We then identified four significantly altered metabolic pathways based on the characteristic metabolites, including glucose metabolism, oxidative stress-related metabolism, energy metabolism, and amino acids metabolism. Comparing CCA cells with normal human umbilical vein endothelial cells (HUVECs), we found that metformin treatment profoundly promoted glycolysis and specifically increased the levels of BCAAs and UDP-GlcNAc, implying the occurrence of autophagy and cell cycle arrest in metformin-treated CAA cells. This work provides a mechanistic understanding of the anticancer effect of metformin treatment on CAA cells, and is beneficial to further developments of metformin as an anticancer drug.

Void defects under track slabs are the main danger affecting the safe operation of high-speed railways. In the short high-speed railway maintenance periods, China’s high-speed railway line maintenance operations must quickly and dynamically determine void defects under track slabs that are in service without contact. However, the detection of void defects under track slabs still mainly relies on the manual inspection and flaw detection by railway workers during the railway maintenance period. If the defects are not quickly identified, the consequences could be disastrous. This article presents a new method for the non-contact dynamic detection of void defects under track slabs. The method involves the use of air-coupled ultrasonic sensors to generate and receive ultrasonic guided waves in the track slab to quantitatively represent the size of the void defect according to the principle of energy leakage of guided waves in the propagation process. The characteristics of the position-amplitude curve, taking the position of the beam axis as the abscissa and the amplitude of the time domain signal as the ordinate, were numerically calculated and analyzed. The quantitative relationship between the convex interval of the position-amplitude curve and the size of the void defect was obtained, and an imaging method of the void defects based on x, y two-dimensional line scanning data fusion is proposed. The excitation and reception methods of air-coupled ultrasonic guided waves were studied, and a 1:1 model of the track structure was built in the laboratory to verify the method and detect the void defect under the track slab. The experimental results show that ultrasonic guided waves can be excited and received in the track slab by air-coupled ultrasonic sensors. Based on the guided wave energy leakage principle, the quantitative characterization and imaging of the void defect under track slabs can be realized.

Expression quantitative trait loci (eQTL) analysis is useful for identifying genetic variants correlated with gene expression, however, it cannot distinguish between causal and nearby non-functional variants. Because the majority of disease-associated SNPs are located in regulatory regions, they can impact allele-specific binding (ASB) of transcription factors and result in differential expression of the target gene alleles. In this study, our aim was to identify functional single-nucleotide polymorphisms (SNPs) that alter transcriptional regulation and thus, potentially impact cellular function. Here, we present regSNPs-ASB, a generalized linear model-based approach to identify regulatory SNPs that are located in transcription factor binding sites. The input for this model includes ATAC-seq (assay for transposase-accessible chromatin with high-throughput sequencing) raw read counts from heterozygous loci, where differential transposase-cleavage patterns between two alleles indicate preferential transcription factor binding to one of the alleles. Using regSNPs-ASB, we identified 53 regulatory SNPs in human MCF-7 breast cancer cells and 125 regulatory SNPs in human mesenchymal stem cells (MSC). By integrating the regSNPs-ASB output with RNA-seq experimental data and publicly available chromatin interaction data from MCF-7 cells, we found that these 53 regulatory SNPs were associated with 74 potential target genes and that 32 (43%) of these genes showed significant allele-specific expression. By comparing all of the MCF-7 and MSC regulatory SNPs to the eQTLs in the Genome-Tissue Expression (GTEx) Project database, we found that 30% (16/53) of the regulatory SNPs in MCF-7 and 43% (52/122) of the regulatory SNPs in MSC were also in eQTL regions. The enrichment of regulatory SNPs in eQTLs indicated that many of them are likely responsible for allelic differences in gene expression (chi-square test, p-value < 0.01). In summary, we conclude that regSNPs-ASB is a useful tool for identifying causal variants from ATAC-seq data. This new computational tool will enable efficient prioritization of genetic variants identified as eQTL for further studies to validate their causal regulatory function. Ultimately, identifying causal genetic variants will further our understanding of the underlying molecular mechanisms of disease and the eventual development of potential therapeutic targets.

Oral squamous cell carcinoma (OSCC) has always been one of the most aggressive and invasive cancers among oral and maxillofacial malignancies. As the morbidity and mortality of the disease have increased year by year, the search for a promising diagnostic and prognostic biomarker for the disease is becoming increasingly urgent. Tumorous and adjacent tissues were collected from three OSCC sufferers and we obtained 229 differentially expressed genes (DEGs) between tumor and normal tissues via high-throughput RNA sequence. Function and pathway enrichment analyses for DEGs were conducted to find a correlation between tumorigenesis status and DEGs. Protein interaction network and molecular complex detection (MCODE) were constructed to detect core modules. Two modules were enriched in MCODE. The diagnostic and prognostic values of the candidate genes were analyzed, which provided evidence for the candidate genes as new tumor markers. Small Proline Rich Protein 3 (SPRR3), a potential tumor marker that may be useful for the diagnosis of OSCC, was screened out. The survival analysis showed that SPRR3 under expression predicted the poor prognosis of OSCC patients. Further experiments have also shown that the expression of SPRR3 decreased as the malignancy of OSCC increased. Therefore, we believe that SPRR3 could be used as a novel diagnostic and prognostic tumor marker.

ABSTRACT Ssr4 serves as a cosubunit of chromatin-remodeling SWI/SNF and RSC complexes in yeasts but remains functionally uncharacterized due to its essentiality for yeast viability. Here, we report pleiotropic effects of the deletion of the ssr4 ortholog nonessential for cell viability in Beauveria bassiana, an asexual insect mycopathogen. The deletion of ssr4 resulted in severe growth defects on different carbon/nitrogen sources, increased hyphal hydrophilicity, blocked hyphal differentiation, and 98% reduced conidiation capacity compared to a wild-type standard. The limited Δssr4 conidia featured an impaired coat with disordered or obscure hydrophobin rodlet bundles, decreased hydrophobicity, increased size, and lost insect pathogenicity via normal cuticle infection and 90% of virulence via intrahemocoel injection. The expression of genes required for hydrophobin biosynthesis and assembly of the rodlet layer was drastically repressed in more hydrophilic Δssr4 cells. Transcriptomic analysis revealed 2,517 genes differentially expressed in the Δssr4 mutant, including 1,505 downregulated genes and 1,012 upregulated genes. The proteins encoded by hundreds of repressed genes were involved in metabolism and/or transport of carbohydrates, amino acids, and lipids, inorganic ion transport and energy production or conversion, including dozens involved in DNA replication, transcription, translation, and posttranslational modifications. However, purified Ssr4 samples showed no DNA-binding activity, implying that the role of Ssr4 in genome-wide gene regulation could rely upon its acting as a cosubunit of the two complexes. These findings provide the first insight into an essential role of Ssr4 in the asexual cycle in vitro and in vivo of B. bassiana and highlights its importance for the filamentous fungal lifestyle. IMPORTANCE Ssr4 is known to serve as a cosubunit of chromatin-remodeling SWI/SNF and RSC complexes in yeasts but has not been functionally characterized in fungi. This study unveils for the first time the pleiotropic effects caused by deletion of ssr4 and its role in mediating global gene expression in a fungal insect pathogen. Our findings confirm an essential role of Ssr4 in hydrophobin biosynthesis and assembly required for growth, differentiation, and development of aerial hyphae for conidiation and conidial adhesion to insect surface and its essentiality for insect pathogenicity and virulence-related cellular events. Importantly, Ssr4 can regulate nearly one-fourth of all genes in the fungal genome in direct and indirect manners, including dozens involved in gene activity and hundreds involved in metabolism and/or transport of carbohydrates, amino acids, lipids, and/or inorganic ions. These findings highlight a significance of Ssr4 for filamentous fungal lifestyle.

Background: Abnormal expression of the orphan nuclear receptor Nurr1 is a critical factor in the etiology of multiple cancers. However, its potential role in gastric cancer (GC) remains elusive. In this study, we have demonstrated that the expression of Nurr1 was elevated and had an oncogenic function in GC. Methods: Nurr1 expression was analyzed in clinical specimens and the GEO database. Functions of Nurr1 in GC cells were analyzed using Nurr1 knockdown and overexpression. Various cell and molecular biological methods were used to explore the potential mechanisms of Nurr1 upregulation and its role in promoting GC. Findings: Overexpression of Nurr1 was directly related to the poor prognosis of GC patients. What's more, Nurr1 was induced by Helicobacter pylori (H. pylori) via the PI3K/AKT-Sp1 pathway. Sp1 enhanced Nurr1 expression by binding to its promoter to activate the transcription. Upregulated Nurr1 then directly targeted CDK4 by binding to its promoter region to increase its expression, thereby facilitated GC cells proliferation both in vitro and in vivo. Interpretation: We identified Nurr1 as a driving oncogenic factor in GC. In addition, Nurr1 could be used as a potential therapeutic target for the diagnosis and treatment of H. pylori-associated GC. Funding: This work was supported by the National Natural Science Foundation of China (Nos 81801983, 81871620, 81971901, 81772151 and 81571960), and the Department of Science and Technology of Shandong Province (2018CXGC1208). Keywords: Gastric cancer, PI3K/AKT/Sp1, Proliferation, CDK4, Helicobacter pylori

Mechanical ventilation strategies that reduce the heterogeneity of regional lung stress and strain may reduce the risk of ventilator-induced lung injury (VILI). In this study, we used registration of four-dimensional computed tomographic (4DCT) images to assess regional lung aeration and deformation in 10 pigs under baseline conditions and following acute lung injury induced with oleic acid. CT images were obtained via dynamic axial imaging (Siemens SOMATOM Force) during conventional pressure-controlled mechanical ventilation (CMV), as well as high-frequency and multi-frequency oscillatory ventilation modalities (HFOV and MFOV, respectively). Our results demonstrate that oscillatory modalities reduce intratidal strain throughout the lung in comparison to conventional ventilation, as well as the spatial gradients of dynamic strain along the dorsal-ventral axis. Harmonic distortion of parenchymal deformation was observed during HFOV with a single discrete sinusoid delivered at the airway opening, suggesting inherent mechanical nonlinearity of the lung tissues. MFOV may therefore provide improved lung-protective ventilation by reducing strain magnitudes and spatial gradients of strain compared to either CMV or HFOV.

The Mann-Kendall (MK) statistical test has been widely applied in the trend detection of the hydrometeorological time series. Previous studies have mainly focused on the null hypothesis of “no trend” or the “Type I Error.” However, few studies address the capability of the MK test to successfully recognize the trends. In some cases, especially when the trend test is jointly applied with hydropower station design, flood risk assessment, and water quality evaluation, the “Type II error” is equally important and should not be neglected. To cope with this problem, we carry out Monte Carlo simulations and the results indicate that in addition to the significance level and the sample length, the MK test power has a close relationship with the sample variance and the magnitude of the trend. For a given time series with fixed length, the power of the MK test increases as the slope increases and declines with increasing sample variance. A deterministic relationship between the slope and the standard deviation of the white noise that can be used for evaluating the power of the MK test has also been detected. Furthermore, we find that a positive autocorrelation contained in the time series will increase both the Type I and the Type II errors due to the enlargement of the variance in the MK statistics. Finally, we recommend that researchers slightly increase the significance level and lengthen the time series sample to improve the power of the MK test in future studies.

In this work, the air pollution index in three cities (Seoul, Busan, and Daegu) in South Korea was studied using multifractal detrended fluctuation analysis (MF-DFA). Hurst, Renyi, and Holder exponents were used to analyze the characteristics of the concentration time series of PM2.5 and NO2. The results showed that multifractality exists in each season interval and the multifractal degree of PM2.5 is stronger than that of NO2. To investigate the effects of the implementation of the “haze special law” on February 15, 2019, we analyzed the time series of PM2.5 during the time periods from February 15, 2018, to December 16, 2018, and February 15, 2019, to December 16, 2019. We found that the multifractal spectrum width after the implementation of the law was narrower than that before the law for all the cities, which shows that the enactment of the law has played a role in improving the efficiency of air pollution control in South Korea. We also conclude that the major effects of the law will be particularly visible in larger cities. To study the main causes of multifractality, the shuffled and phase-randomized series were analyzed using MF-DFA, and the results demonstrated that the fat-tailed distribution resulted in the multifractality of the time series before and after the implementation of the “haze special law” in Seoul and Daegu, whereas long-range correlation resulted in multifractality of the series before and after the implementation of the law in Busan.

In this paper, lightweight carbon/carbon fiber composite thermal field insulation materials were fabricated by the process method of long carbon fiber airflow netting-needle punching forming felt-resin impregnation-molding curing-high-temperature carbonization and graphitization. The microscopic morphology, conductivity, bending strength, and thermal conductivity of carbon/carbon fiber composites were measured by using the scanning electron microscope (SEM), four probes, electronic universal testing machine, and thermal analyzer. The results show that the long carbon fiber in the carbon/carbon fiber composite forms a three-dimensional structure of X-Y-Z with a density of 0.16 ± 0.02 g/cm3, which makes the composite material have excellent thermal insulation performance at high temperature, and the conductivity is 1452.4 S/m (plane direction) and 182.8 S/m (perpendicular to the plane direction), the compressive strength is 0.2 MPa (plane direction) and 1.31 MPa (perpendicular to the plane direction), the bending strength is 0.24 MPa (plane direction) and 1.1 MPa (perpendicular to the plane direction), and the thermal conductivity is 0.076 W/(mK) (25°C) and 0.17 W/(mK) (1200°C), respectively. The above process methods and test results will provide the application of the carbon/carbon fiber composite in the solar polysilicon furnace, single crystal silicon furnace, semiconductor furnace, sapphire furnace, fiber drawing furnace, and high-end metallurgical heat treatment furnaces, as well as applications in other high-temperature insulation environments, and also provide some suggestions in these insulation applications.

The study region was the East Asian summer monsoon (EASM) transition zone. The datasets used in this study included the daily data of national stations, reanalysis datasets of the European Centre for Medium-Range Weather Forecasts (ECMWF), Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) and Moderate Resolution Imaging Spectroradiometer (MODIS) data. All datasets covered a total period of more than 1 year (from January 2008 to December 2016). We analyzed the influence of EASM on aerosol optical depth (AOD) in the transition zone and the response of different types of aerosols in the transition zone to the abundant and deficient monsoon years. It was found that the AOD was 0.15 in abundant years, while it was 0.09 in deficient years. The abundant year’s AOD was 40% larger than deficient years. In deficient years, with less precipitation, the influence of precipitation on the AOD was more significant. The dust was mainly distributed at 2–6 km in the western part of the transition zone, while the polluted aerosols were distributed at 0–4 km in the central and eastern region. The frequency of dust was significantly lower in abundant years, and dust particles accounted for about 19.6%. The frequency of polluted aerosols had an opposite trend, accounting for about 71.8%. Our findings bringed insight into the vertical distribution of aerosols in the atmospheric boundary layer and the interannual variation over the transition zone.

COVID-19 vaccines were first administered on 15 December 2020, marking an important transition point for the spread of SARS-CoV-2 in the United States (U.S.). Prior to this point in time, the virus spread to an almost completely immunologically naïve population, whereas subsequently, vaccine-induced immune pressure and prior infections might be expected to influence viral evolution. Accordingly, we conducted a study to characterize the spread of SARS-CoV-2 in the U.S. pre-vaccination, investigate the depth and uniformity of genetic surveillance during this period, and measure and otherwise characterize changing viral genetic diversity, including by comparison with more recently emergent variants of concern (VOCs). In 2020, SARS-CoV-2 spread across the U.S. in three phases distinguishable by peaks in the numbers of infections and shifting geographical distributions. Virus was genetically sampled during this period at an overall rate of ~1.2%, though there was a substantial mismatch between case rates and genetic sampling nationwide. Viral genetic diversity tripled over this period but remained low in comparison to other widespread RNA virus pathogens, and although 54 amino acid changes were detected at frequencies exceeding 5%, linkage among them was not observed. Based on our collective observations, our analysis supports a targeted strategy for worldwide genetic surveillance as perhaps the most sensitive and efficient means of detecting new VOCs.

Background: There is considerable discordance in the curve progression of adolescent idiopathic scoliosis (AIS) patients between monozygotic (MZ) twins, indicating that nongenetic factors must be involved in the curve progression of AIS patients. Epigenetic processes may constitute one of these factors and have not yet been investigated in relation to curve progression in AIS patients. Methods: The genome and methylome of peripheral monocytes were compared between MZ twins discordant for curve progression. Sets of differentially methylated sites were validated using the MassARRAY platform of Sequenome on additional samples. Results: In the discovery study, we found evidence suggesting a lack of differences at the genome sequence level and the presence of epigenetic differences related to the curve progression of AIS patients. The top 4 differentially methylated CpG sites associated with curve severity were tested, and only site cg01374129 (CpG site located at chr8:122583383, Hg19) was confirmed in two replication cohorts. The methylation levels of site cg01374129 were significantly lower in the progression group than in the nonprogression group. Cox regression analysis demonstrated that hypo-methylation of site cg01374129 was an independent prognostic factor for curve severity. Site cg01374129 methylation as a marker achieved a sensitivity of 76.4% and a specificity of 85.6% in differentiating between samples from patients with and without curve progression (AUC = 0.827; 95% CI: 0.780 to 0.876). Conclusion: Increased curvature is associated with decreased methylation at site cg01374129. Our results indicate that methylation of site cg01374129 may therefore serve as a promising biomarker in differing between patients with and without curve progression. Keywords: Adolescent idiopathic scoliosis, Progression, Whole genome sequencing, Methylation, Predictor

Abstract Background Adolescent idiopathic scoliosis (AIS) is the most common paediatric spinal deformity. The etiology and pathology of AIS remain unexplained, and have been reported to involve a combination of genetic and epigenetic factors. Since paravertebral muscle imbalance plays an important role in the onset and progression of scoliosis, we aimed to investigate transcriptomic differences by RNA-seq and identify significantly differentially expressed transcripts in two sides of paravertebral muscle in AIS. Methods RNA-seq was performed on 5 pairs of paravertebral muscle from 5 AIS patients. Significantly differentially expressed transcripts were validated by quantitative reverse polymerase chain reaction. Gene expression difference was correlated to clinical characteristics. Results We demonstrated that ADIPOQ mRNA and H19 is significantly differentially expressed between two sides of paravertebral muscle, relatively specific in the context of AIS. Relatively low H19 and high ADIPOQ mRNA expression levels in concave-sided muscle are associated with larger spinal curve and earlier age at initiation. We identified miR-675-5p encoded by H19 as a mechanistic regulator of ADIPOQ expression in AIS. We demonstrated that significantly reduced CCCTC-binding factor (CCTF) occupancy in the imprinting control region (ICR) of the H19 gene in the concave-sided muscle contributes to down-regulated H19 expression. Conclusions RNA-seq revealed transcriptomic differences between two sides of paravertebral muscle in AIS patients. Our findings imply that transcriptomic differences caused by epigenetic factors in affected individuals may account for the structural and functional imbalance of paravertebral muscle, which can expand our etiologic understanding of this disease.

Abstract Background Amplified inflammation is important for the progression of Parkinson’s disease (PD). However, how this enhanced inflammation is regulated remains largely unknown. Deletion of DICER leads to progressive dopamine neuronal loss and induces gliosis. We hypothesized that the homeostasis of microglial DICER would be responsible for the amplified inflammation in the mouse model of PD. Methods The microglia or C57BL/6 mice were treated or injected with l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) or 1-methyl-4-phenylpyridinium (MPP+), respectively, for the model establishment. Microglia and astrocytes sorted by fluorescence-activated cell sorter (FACS) were assayed by quantitative real-time PCR, Western blotting, immunoprecipitation, enzyme-linked immunosorbent assay (ELISA), immunohistofluorescence, and mass spectrometry. Results Microglial DICER was phosphorylated at serine 1456 by c-jun N-terminal kinase (JNK) and downregulated in response to 1-methyl-4-phenylpyridinium (MPP+), a causative agent in PD. Inhibition of JNK phosphorylation of DICER at serine 1456 rescued the MPP+-induced DICER degradation, suppressed microglial inflammatory process, and prevented the loss of tyrosine hydroxylase-expressing neurons in the mouse MPTP model. Conclusions JNK-mediated microglial DICER degradation potentiates inflammation to induce dopaminergic neuronal loss. Thus, preventing microglial DICER degradation could be a novel strategy for controlling neuroinflammation in PD.

With data mining techniques for the preprocessing of training patterns, an artificial neural network (ANN) model is proposed for parametric modeling of electromagnetic behavior of ultrawide band (UWB) antennas in this paper. In this ANN method, two data mining techniques, including correlation analysis and data classification based on support vector machine (SVM), are employed to determine geometrical variable inputs and classify the inputs during the training and testing processes. Compared with the traditional ANN, the proposed model with data mining can achieve the trained model with small training datasets and accurate results. The validity and efficiency of this proposed method are confirmed with two band-notched UWB antenna examples.

Abstract Metastasis is the leading cause of human cancer deaths. Unfortunately, no approved drugs are available for anti-metastatic treatment. In our study, high-throughput sequencing-based high-throughput screening (HTS2) and a breast cancer lung metastasis (BCLM)-associated gene signature were combined to discover anti-metastatic drugs. After screening of thousands of compounds, we identified Ponatinib as a BCLM inhibitor. Ponatinib significantly inhibited the migration and mammosphere formation of breast cancer cells in vitro and blocked BCLM in multiple mouse models. Mechanistically, Ponatinib represses the expression of BCLM-associated genes mainly through the ERK/c-Jun signaling pathway by inhibiting the transcription of JUN and accelerating the degradation of c-Jun protein. Notably, JUN expression levels were positively correlated with BCLM-associated gene expression and lung metastases in breast cancer patients. Collectively, we established a novel approach for the discovery of anti-metastatic drugs, identified Ponatinib as a new drug to inhibit BCLM and revealed c-Jun as a crucial factor and potential drug target for BCLM. Our study may facilitate the therapeutic treatment of BCLM as well as other metastases.

Based on the explicit finite-difference time-domain (FDTD) and implicit Crank–Nicolson (CN) FDTD methods, this paper presents a hybrid sub-gridded scheme whose time step size depends on the coarse grid size for numerically simulating the 3-D ground penetrating radar (GPR) scenarios in lossy, dispersive, and inhomogeneous soils. The time step size of CN-FDTD is independent of the grid size in the dense grid region due to its unconditional stability. Thus, the whole region can be run with a time step size determined by the coarse grid in an absolutely stable fashion. Moreover, a multi-pole Debye dispersion model, solved with auxiliary differential equations (ADEs) for both FDTD and CN-FDTD, is incorporated to simulate realistic GPR scenarios, including the detection of different objects buried in dispersive soils. In order to reduce the matrix size of the 3-D implicit CN-FDTD method, the domain decomposition technique is originally employed to achieve fast calculation. Several numerical examples of the GPR scenarios are provided to demonstrate the accuracy and efficiency of the hybrid sub-gridded ADE-FDTD method.

Long noncoding RNAs (lncRNAs) are defined as transcripts with more than 200 nucleotides that have little or no coding potential. In recent years, due to the development of next-generation sequencing (NGS), a large number of studies have revealed that lncRNAs function as key regulators to maintain immune balance and participate in diverse physiological and pathological processes in the human body. Notably, overwhelming evidence suggests that lncRNAs can regulate innate immune responses, the differentiation and development of immune cells, inflammatory autoimmune diseases, and many other immunological processes with distinct regulatory mechanisms. In this review, we summarized the emerging roles of lncRNAs in macrophage development and polarization. In addition, the potential value of lncRNAs as diagnostic biomarkers and novel therapeutic targets for the treatment of aberrant immune responses and inflammatory diseases are discussed.

Quantification of uncertainties associated with satellite precipitation products is a prior requirement for their better applications in earth science studies. An improved scheme is developed in this study to decompose mean bias error (MBE) and mean square error (MSE) into three components, i.e., MBE and MSE associated hits, missed precipitation, and false alarms, respectively, which are weighted by their relative frequencies of occurrence (RFO). The trend of total MBE or MSE is then naturally decomposed into six components according to the chain rule for derivatives. Quantitative estimation of individual contributions to total MBE and MSE is finally derived. The method is applied to validation of Integrated MultisatellitE Retrievals for GPM (IMERG) in Mainland China. MBE associated with false alarms is an important driver for total MBE, while MSE associated with hits accounts for more than 85% of MSE, except in inland semi-arid area. The RFO of false alarms increases, whereas the RFO of missed precipitation decreases. Both factors lead in part to a growing trend for total MBE. Detection of precipitation should be improved in the IMERG algorithm. More specifically, the priority should be to reduce false alarms.

Pure Copper (Cu) is very difficult to prepare using selective laser melting (SLM) technology. This work successfully prepared the pure Cu with high relative density and high strength by the SLM technology using a surface oxidation treatment. The gas-atomized pure Cu powder was used as the feedstock in this work. Before the SLM process, the pure Cu powder was initially handled using the surface oxidation treatment to coat the powder with an extremely thin layer of Cu2O. The SLMed highly dense specimens contain α-Cu and nano-Cu2O phases. A relationship between the processing parameters (laser power (LP), scanning speed (SS), and hatch space (HS)) and density of Cu alloy in SLM was also investigated. The microstructure of SLMed Cu consists of fine grains with grain sizes ranging from 0.5 to ~30 μm. Tensile testing and detailed microstructural characterization were performed on specimens in the as-SLMed and pure copper state specimens. The mechanical property experiments showed that the specimens prepared by SLM technology containing nano-oxide phases had higher yield strength and tensile strength than that of other SLM-built pure copper. However, the elongation was remarkably decreased compared to other SLM-built pure copper, due to the fine grains and the nano-oxides.

Wheel rail rolling contact fatigue is a very common form of damage, which can lead to uneven rail treads, railhead nuclear damage, etc. Therefore, ANSYS software was used to establish a three-dimensional wheel–rail contact model and analyze the effects of several main characteristics, such as the rail crack length and crack propagation angle, on the fatigue crack intensity factor during crack propagation. The main findings were as follows: (1) With the rail crack length increasing, the position where the crack propagated by mode I moved from the inner edge of the wheel–rail contact spot to the outer edge. When the crack propagated to 0.3–0.5 mm, it propagated to the rail surface, causing the rail material to peel or fall off and other damage. (2) When the crack propagation angle was less than 30°, the cracks were mainly mode II cracks. When the angle was between 30 and 70°, the cracks were mode I–II cracks. When the angle was more than 70°, the cracks were mainly mode I cracks. When the crack propagation angle was 60°, the equivalent stress intensity factor reached the maximum, and the rail cracks propagated the fastest.

It is important for aquaculture monitoring, scientific planning, and management to extract offshore aquaculture areas from medium-resolution remote sensing images. However, in medium-resolution images, the spectral characteristics of offshore aquaculture areas are complex, and the offshore land and seawater seriously interfere with the extraction of offshore aquaculture areas. On the other hand, in medium-resolution images, due to the relatively low image resolution, the boundaries between breeding areas are relatively fuzzy and are more likely to ‘adhere’ to each other. An improved U-Net model, including, in particular, an atrous spatial pyramid pooling (ASPP) structure and an up-sampling structure, is proposed for offshore aquaculture area extraction in this paper. The improved ASPP structure and up-sampling structure can better mine semantic information and location information, overcome the interference of other information in the image, and reduce ‘adhesion’. Based on the northeast coast of Fujian Province Sentinel-2 Multispectral Scan Imaging (MSI) image data, the offshore aquaculture area extraction was studied. Based on the improved U-Net model, the F1 score and Mean Intersection over Union (MIoU) of the classification results were 83.75% and 73.75%, respectively. The results show that, compared with several common classification methods, the improved U-Net model has a better performance. This also shows that the improved U-Net model can significantly overcome the interference of irrelevant information, identify aquaculture areas, and significantly reduce edge adhesion of aquaculture areas.

This study investigated the effect of moderate risk level (8 µg/kg) AFB1 in diet supplemented with or without adsorbents on lactation performance, serum parameters, milk AFM1 content of healthy lactating cows and the AFM1 residue exposure risk in different human age groups. Forty late healthy lactating Holstein cows (270 ± 22 d in milk; daily milk yield 21 ± 3.1 kg/d) were randomly assigned to four treatments: control diet without AFB1 and adsorbents (CON), CON with 8 μg/kg AFB1 (dry matter basis, AF), AF + 15 g/d adsorbent 1 (AD1), AF + 15 g/d adsorbent 2 (AD2). The experiment lasted for 19 days, including an AFB1-challenge phase (day 1 to 14) and an AFB1-withdraw phase (day 15 to 19). Results showed that both AFB1 and adsorbents treatments had no significant effects on the DMI, milk yield, 3.5% FCM yield, milk components and serum parameters. Compared with the AF, AD1 and AD2 had significantly lower milk AFM1 concentrations (93 ng/L vs. 46 ng/L vs. 51 ng/L) and transfer rates of dietary AFB1 into milk AFM1 (1.16% vs. 0.57% vs. 0.63%) (p < 0.05). Children aged 2–4 years old had the highest exposure risk to AFM1 in milk in AF, with an EDI of 1.02 ng/kg bw/day and a HI of 5.11 (HI > 1 indicates a potential risk for liver cancer). Both AD1 and AD2 had obviously reductions in EDI and HI for all population groups, whereas, the EDI (≥0.25 ng/kg bw/day) and HI (≥1.23) of children aged 2–11 years old were still higher than the suggested tolerable daily intake (TDI) of 0.20 ng/kg bw/day and 1.00 (HI). In conclusion, moderate risk level AFB1 in the diet of healthy lactating cows could cause a public health hazard and adding adsorbents in the dairy diet is an effective measure to remit AFM1 residue in milk and its exposure risk for humans.

With the development of sensors and of the Internet of Things (IoT), smart cities can provide people with a variety of information for a more convenient life. Effective on-street parking availability prediction can improve parking efficiency and, at times, alleviate city congestion. Conventional methods of parking availability prediction often do not consider the spatial–temporal features of parking duration distributions. To this end, we propose a parking space prediction scheme called the hybrid spatial–temporal graph convolution networks (HST-GCNs). We use graph convolutional networks and gated linear units (GLUs) with a 1D convolutional neural network to obtain the spatial features and the temporal features, respectively. Then, we construct a spatial–temporal convolutional block to obtain the instantaneous spatial–temporal correlations. Based on the similarity of the parking duration distributions, we propose an attention mechanism called distAtt to measure the similarity of parking duration distributions. Through the distAtt mechanism, we add the long-term spatial–temporal correlations to our spatial–temporal convolutional block, and thus, we can capture complex hybrid spatial–temporal correlations to achieve a higher accuracy of parking availability prediction. Based on real-world datasets, we compare the proposed scheme with the benchmark models. The experimental results show that the proposed scheme has the best performance in predicting the parking occupancy rate.

A superhydrophobic fluorinated silica functionalized chitosan (F-CS) aerogel is constructed and fabricated by a simple and sustainable method in this study in order to achieve highly efficient gravity-driven oil/water separation performance. The fluorinated silica functionalization invests the pristine hydrophilic chitosan (CS) aerogel with promising superhydrophobicity with a water contact angle of 151.9°. This novel F-CS aerogel possesses three-dimensional structure with high porosity as well as good chemical stability and mechanical compression property. Moreover, it also shows striking self-cleaning performance and great oil adsorption capacity. Most importantly, the as-prepared aerogels exhibits fast and efficient separation of oil/water mixture by the gravity driven process with high separation efficiency. These great performances render the prepared F-CS aerogel a good candidate for oil/water separation in practical industrial application.

High temperatures can enhance the chloride diffusion coefficient and this poses a threat to reinforced concrete (RC) piles. This study intends to propose predictive models that can evaluate the service life and lateral bearing behaviour of reinforced concrete piles subjected to marine environments and varying temperatures. The models show that temperature can accelerate the diffusion rate of chloride and increase the concentration of free chloride in concrete. The distribution law of chloride concentration is obtained by considering the ageing effect as well. Deterministic and probabilistic models are proposed to assess the time to corrosion initiation and propagation. The stiffness degradation coefficient is introduced in the analysis of the lateral bearing capacity of RC piles. The results show that high temperature can decrease the service life of piles and the life spans obtained from deterministic and probabilistic methods are similar; however, the predictions of the latter are more conservative. Temperature can enhance the current density and boost corrosion products, which leads to pile cracking. The rust appearing on the steel surface would make the stiffness degradation coefficient drop sharply. The lateral bearing capacity analysis is conducted from the perspectives of shear force, displacement and bearing moment of the piles.

Abstract Background Schistosomiasis is one of the most common parasitic diseases affecting millions of humans and animals worldwide. Understanding the signal transduction pathways and the molecular basis of reproductive regulation in schistosomes is critically important for developing new strategies for preventing and treating these infections. Syk kinases regulate the proliferation, differentiation, morphogenesis, and survival of various types of cells and have been identified in invertebrates. Tyrosine kinase 4 (TK4), a member of the Syk kinase family, plays a pivotal role in gametogenesis in S. mansoni, affecting the development of the testis and ovaries in this parasite. The role of TK4, however, in the reproduction of S. japonicum is poorly understood. Methods Here, the complete coding sequence of TK4 gene in S. japonicum (SjTK4) was cloned and characterized. The expression of SjTK4 was analyzed at different life-cycle stages and in various tissues of S. japonicum by qPCR. Piceatannol, a Syk kinase inhibitor, was applied to S. japonicum in vitro. The piceatannol-induced morphological changes of the parasites were observed using confocal laser scanning microscopy and the alterations in important egg-shell synthesis-related genes were examined using qPCR analyses. Results SjTK4 mRNA was differentially expressed throughout the life-cycle of S. japonicum. SjTK4 mRNA was highly expressed in the ovary and testis of S. japonicum, with the level of gene expression significantly higher in males than in females. The expression levels of some important egg-shell synthesis related genes were higher in the piceatannol-treated groups than in the vehicle-treated control group and the number of eggs and germ cells also decreased in a concentration-dependent manner. Importantly, large pore-like structures can be found in the testis and ovaries of males and females after treating with piceatannol. Conclusion The results suggest that SjTK4 may play an important role in regulating gametogenesis of S. japonicum. The findings may help better understand the fundamental biology of S. japonicum. Moreover, the effect of S. japonicum treatment by piceatannol provides us with a new idea that inhibition of SjTK4 signaling pathway can effectively retard the development of the testis and ovaries.

Abstract The association between air pollution and childhood respiratory disease is inconsistent. In the present study, we investigated a short-term effect of ambient air pollutants and daily childhood lower respiratory diseases (CLRD). Daily air pollutants, weather data, and CLRD data were collected from January 2014 to April 2015 (452 days) in Nanjing, China. Time-series regression and generalized additive models were used to assess the effects of air pollutants (PM10, PM2.5, NO2, SO2, O3, and CO) on CLRD. We observed that an interquartile range (IQR) increase in concentrations of PM10, NO2, and SO2 significantly increased the daily CLRD with 6 days cumulative effects (difference of estimates: 2.8%, 95% CI: 0.6–5.0%; 4.1%, 1.2–7.0%; 5.6%, 2.6–8.6%, respectively). However, no significant association was found in IQR concentrations of PM2.5, O3, and CO. Specifically, elevated PM10, PM2.5, NO2, and SO2 significantly increased the numbers of CLRD in cool season (3.6%, 1.5–5.7%; 2.4%, 0.3–4.5%; 4.9%, 2.9–7.0%; 6.3%, 3.7–9.0%, respectively). Additionally, the effect estimates of PM10, NO2, and SO2 in female and age >27 months were more pronounced than in male and age ≤27 months. This study suggested that short-term exposure to ambient PM10, NO2, and SO2 were associated with the increased CLRD numbers.

Abstract Purpose: To investigate the effects of dexmedetomidine (DEX) on amino acid contents and the cerebral ultrastructure of rats with cerebral ischemia-reperfusion injury (I/R). Methods: Thirty-six, male, Wistar rats were randomly divided into three groups: the sham operation group (group C), the ischemia-reperfusion group (group I/R), and the DEX group (group D). The middle cerebral artery occlusion model was prepared by the modified Longa method. The time of ischemia was 180 min, and 120 min after reperfusion, the amount of glutamate (Glu), and γ-aminobutyric acid (GABA) in the brain were measured, and the ultrastructure-level changes in the cerebral cortex were examined using electron microscopy. Results: Compared to group C, Glu contents in group D, and I/R significantly increased. Compared to group I/R, Glu contents in group D significantly decreased. Compared to group C, GABA contents in group D, and I/R significantly increased, and those in group D significantly increased, as compared to group I/R. The cerebral ultrastructure was normal in group C. Vacuolar degeneration in the plastiosome and nervous processes, was more critical than in group D. Vascular endothelial cells (VEC) were damaged. On the contrary, these changes in group D significantly improved. Conclusion: Dexmedetomidine is capable of decreasing glutamergic content, and increasing GABAergic content, in order to decrease the injury of the cerebral ultrastructure, following cerebral ischemia-reperfusion injury.

Abstract Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary tumor in the central nervous system. One of the most widely used chemotherapeutic drugs for GBM is temozolomide, which is a DNA-alkylating agent and its efficacy is dependent on MGMT methylation status. Little progress in improving the prognosis of GBM patients has been made in the past ten years, urging the development of more effective molecular targeted therapies. Hyper-activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is frequently found in a variety of cancers including GBM, and it plays a central role in the regulation of tumor cell survival, growth, motility, angiogenesis and metabolism. Numerous PI3K inhibitors including pan-PI3K, isoform-selective and dual PI3K/mammalian target of rapamycin (mTOR) inhibitors have exhibited favorable preclinical results and entered clinical trials in a range of hematologic malignancies and solid tumors. Furthermore, combination of inhibitors targeting PI3K and other related pathways may exert synergism on suppressing tumor growth and improving patients’ prognosis. Currently, only a handful of PI3K inhibitors are in phase I/II clinical trials for GBM treatment. In this review, we focus on the importance of PI3K/Akt pathway in GBM, and summarize the current development of PI3K inhibitors alone or in combination with other inhibitors for GBM treatment from preclinical to clinical studies.

In this paper, an efficient domain decomposition (DD) technique is originally introduced into the unconditionally stable Crank-Nicolson finite-difference time-domain (CN-FDTD) method for analyzing the extraordinary optical transmission (EOT) phenomenon of periodic metallic gratings. Being caused by the evanescent waves propagating along the metal-dielectric interface in the visible and near infrared regions, the dispersion of the considered metal in this case is expressed by the Drude model and solved with a generalized auxiliary differential equation (ADE) technique. The periodic boundary condition is applied to the two-dimensional periodic metallic grating structures due to their periodicity. Then, the standard unsplit-field perfectly matched layer is derived as the absorbing boundary condition for CN-FDTD based on the ADE concept. In DD structures, the whole computational domain is divided into several subdomains to reduce the matrix size and save calculating time. Furthermore, the reverse Cuthill-Mckee scheme for the lower-upper decomposition is applied to the subdomain matrices individually to improve the efficiency of DD-CN-FDTD. Finally, two numerical examples are calculated and the physical mechanism of the EOT phenomenon is investigated. The results from the proposed method demonstrate its accuracy and efficiency for the nanostructures.

BackgroundHIV-1 proviruses can persist during ART in clonally-expanded populations of CD4+ T cells. To date, few examples of an expanded clones containing replication-competent proviruses exist, although it is suspected to be common. One such clone, denoted AMBI-1 (Maldarelli et al., 2014), was also a source of persistent viremia on ART, begging the question of how the AMBI-1 clone can survive despite infection with a replication-competent, actively-expressing provirus. We hypothesized that only a small fraction of cells within the AMBI-1 clone are activated to produce virus particles during cell division while the majority remain latent despite division, ensuring their survival. To address this question, we determined the fraction of HIV-1 proviruses within the AMBI-1 clone that expresses unspliced cell-associated RNA during ART and compared this fraction to 33 other infected T cell clones within the same individual.ResultsIn total, 34 different clones carrying either intact or defective proviruses in “Patient 1” from Maldarelli et al. (2014) were assessed. We found that 2.3% of cells within the AMBI-1 clone contained unspliced HIV-1 RNA. Highest levels of HIV-1 RNA were found in the effector memory (EM) T cell subset. The fraction of cells within clones that contained HIV-1 RNA was not different in clones with intact (median 2.3%) versus defective (median 3.5%) proviruses (p = 0.2). However, higher fractions and levels of RNA were found in cells with proviruses containing multiple drug resistance mutations, including those contributing to rebound viremia.ConclusionThese findings show that the vast majority of HIV-1 proviruses within expanded T cell clones, including intact proviruses, may be transcriptionally silent at any given time, implying that infected T cells may be able to be activated to proliferate without inducing the expression of the integrated provirus or, alternatelively, may be able to proliferate without cellular activation. The results of this study suggest that the long, presumed correlation between the level of cellular and proviral activation may not be accurate and, therefore, requires further investigation.

To date, most assays for measuring the human immunodeficiency virus (HIV-1) reservoir do not include memory CD4+ T-cells expressing the activation marker, human leukocyte antigen-antigen D related (HLA-DR). However, little is known concerning the role these cells play in maintaining persistent HIV-1 during effective antiretroviral therapy (ART). To address this issue, we examined, cellular activation/exhaustion markers (Ki67, CCR5, PD-1, Lag-3 and Tim-3) and viral gag-pol DNA sequences within HLA-DR− and HLA-DR+ memory CD4+ T-cell subsets longitudinally from the peripheral blood of six participants over 3 to ≥15 years of effective therapy. HLA-DR expression was readily detected during the study period in all participants. The average expression levels of CCR5, PD-1 and Tim-3 were higher on the HLA-DR+ T-cell subset whereas the average of LAG-3 expression was higher on their HLA-DR− counterpart. The proportion of HIV-infected cells increased within the HLA-DR+ subset by an average of 18% per year of ART whereas the frequency of infected HLA-DR− T-cells slightly decreased over time (5% per year). We observed that 20–33% of HIV-DNA sequences from the early time points were genetically identical to viral sequences from the last time point within the same cell subset during ART. This indicates that a fraction of proviruses persists within HLA-DR+ and HLA-DR− T-cell subsets during prolonged ART. Our HIV-DNA sequence analyses also revealed that cells transitioned between the HLA-DR+ and HLA-DR− phenotypes. The Ki67 expression, a marker for cellular proliferation, and the combined markers of Ki67/PD-1 averaged 19-fold and 22-fold higher on the HLA-DR+ T-cell subset compared to their HLA-DR− counterpart. Moreover, cellular proliferation, as reflected by the proportion of genetically identical HIV-DNA sequences, increased within both T-cell subsets over the study period; however, this increase was greater within the HLA-DR+ T-cells. Our research revealed that cellular transition and proliferation contribute to the persistence of HIV in HLA-DR+ and HLA-DR− T-cell subsets during prolonged therapy. As such, the HIV reservoir expands during effective ART when both the HLA-DR+ and HLA-DR− cell subsets are included, and therapeutic interventions aimed at reducing the HIV-1 reservoir should target HLA-DR+ and HLA-DR− T-cells.

This paper presents an ultrasonic Lamb wave imaging method based on time-domain topological energy to address artifacts in the results of traditional ultrasound imaging methods. This method is based on topological theory and the calculation of the direct and adjoint sound fields in a defect-free reference medium. It focuses the direct and adjoint sound fields at the cavity defect using time reversal and their time-domain topological energy as the pixel values of the image to reduce the artifacts. The physical mechanism of time-domain topological energy (TDTE) imaging is revealed by finite element simulation and experiment. The feasibility of this method for multilayer concrete cavity defect imaging is verified. Compared with the traditional synthetic aperture focusing technique (SAFT) imaging method, the numerical simulation and experimental results show that the method can overcome the influence of ultrasonic Lamb wave dispersion and locate cavity defects with high accuracy and few artifacts. These features indicate the potential of the method in imaging damage concrete structures.

It has been recognized that pore water pressure (PWP) changes in response to precipitation play a critical role in rainfall-triggered landslides. Tank models as a kind of undetermined model are widely applied for estimating groundwater levels in slopes. Most of these applications treat the tank models as a theoretical model. Therefore, in this study, physical tank experiments are reported, indicating an evaluation of three typical conceptual tank models (i.e., simple tank model, surface runoff tank model, and lateral water flow supply tank model). To reduce the slope structure controlling affection, the study takes homogenous soil material as the simulation of the slope mass. The experimental results demonstrated how the groundwater tables producing pore water pressure were affected by infiltration time lags, surface runoff, and lateral flow.

The rhizosphere microenvironment is the site of nutrient circulation and microbial community formation, and thus is an ongoing topic of research. Although research on this topic is extensive, studies into the rhizosphere microenvironment of fruit trees remain rare. To elucidate the mechanisms driving the fruit tree rhizosphere microenvironment, we assessed soil physicochemical properties, enzyme activities, the community-level physiological profile (CLPP) and microbial diversity in rhizospheric soils of eight common deciduous fruit trees in northern China. We found that the available minerals, pH, enzyme activities, microbial utilization of six types of carbon (C) substrates, and microbial diversity in the rhizosphere varied among tree species. Redundancy analysis (RDA) showed that rhizosphere microenvironmental parameters (ammonia nitrogen content, soil pH and invertase activity) were closely related to the soil microbial community. Further analysis revealed that the soil microbial utilization of six C sources, nitrate nitrogen content, and invertase activity were negatively correlated with Ambiguous species and Alternaria; however, these groups were positively correlated with pH. The ammonia nitrogen content was positively correlated with C source utilization and negatively correlated with Ambiguous, Lysobacter, Nitrospira, Alternaria, Fusarium, and Colletotrichum. Interestingly, invertase was closely linked to the microbial community, especially fungal diversity, and was positively correlated with plant-beneficial microbes such as Mortierella, Geomyces, Lysobacter, and Chaetomium, but negatively correlated with pathogenic microbes such as Alternaria, Fusarium, and Colletotrichum. Hence, rhizosphere soil physicochemical properties, enzyme activities and microbial community were significantly affected by tree species. Additionally, a variety of environmental factors were closely related to the microbial community in the rhizospheric soils of eight species of deciduous fruit trees.

The latent HIV-1 reservoir is comprised of stably integrated and intact proviruses with limited to no viral transcription. It has been proposed that latent infection may be maintained by methylation of pro-viral DNA. Here, for the first time, we investigate the cytosine methylation of a replication competent provirus (AMBI-1) found in a T cell clone in a donor on antiretroviral therapy (ART). Methylation profiles of the AMBI-1 provirus were compared to other proviruses in the same donor and in samples from three other individuals on ART, including proviruses isolated from lymph node mononuclear cells (LNMCs) and peripheral blood mononuclear cells (PBMCs). We also evaluated the apparent methylation of cytosines outside of CpG (i.e., CpH) motifs. We found no evidence for methylation in AMBI-1 or any other provirus tested within the 5′ LTR promoter. In contrast, CpG methylation was observed in the env-tat-rev overlapping reading frame. In addition, we found evidence for differential provirus methylation in cells isolated from LNMCs vs. PBMCs in some individuals, possibly from the expansion of infected cell clones. Finally, we determined that apparent low-level methylation of CpH cytosines is consistent with occasional bisulfite reaction failures. In conclusion, our data do not support the proposition that latent HIV infection is associated with methylation of the HIV 5′ LTR promoter.

As the heat flux of electronic components is increasing rapidly, the traditional air-cooling technique is gradually not meeting the requirements of thermal management. The immersion liquid-cooling technique shows great potential, and has attracted increasing attention due to its excellent performance in recent years. The finned heat sink is common and essential for cooling electric components. To analyze the influences of its structural parameters on heat dissipation and improve its efficiency while using a dielectric coolant, this study used the orthogonal analysis method to obtain the optimal structure via the numerical simulation method. The maximum temperature of the heat sink was selected as the evaluation criteria. The results showed that the parameters that affect the maximum temperature, in order of importance, are fin thickness, the number of fins, the height of the fins, and substrate thickness. Finally, taking the maximum temperature and mass as indexes obtained the optimal structure of the heat sink. The mass was reduced by 19%, while the temperature only increased by 4.5% when considering the mass index.

Treatment of HIV-1 infected patients with latency-reversing agents (LRA) induces transcription of proviruses in CD4 T cells. Using single-genome sequencing, the authors show that the LRA-induced CD4 T cell-associated HIV RNA is genetically diverse and contains a high proportion of defective RNA.

Sterol regulatory element-binding protein (SREBP) transcription factors are central regulators of cellular lipid homeostasis and activate expression of genes required for fatty acid, triglyceride, and cholesterol synthesis and uptake. SREBP cleavage activating protein (SCAP) plays an essential role in SREBP activation by mediating endoplasmic reticulum (ER)-to-Golgi transport of SREBP. In the Golgi, membrane-bound SREBPs are cleaved sequentially by the site-1 and site-2 proteases. Recent studies have shown a requirement for the SREBP pathway in the development of fatty liver disease and tumor growth, making SCAP a target for drug development. Fatostatin is a chemical inhibitor of the SREBP pathway that directly binds SCAP and blocks its ER-to-Golgi transport. In this study, we determined that fatostatin blocks ER exit of SCAP and showed that inhibition is independent of insulin-induced gene proteins, which function to retain the SCAP-SREBP complex in the ER. Fatostatin potently inhibited cell growth, but unexpectedly exogenous lipids failed to rescue proliferation of fatostatin-treated cells. Furthermore, fatostatin inhibited growth of cells lacking SCAP. Using a vesicular stomatitis virus glycoprotein (VSVG) trafficking assay, we demonstrated that fatostatin delays ER-to-Golgi transport of VSVG. In summary, fatostatin inhibited SREBP activation, but fatostatin additionally inhibited cell proliferation through both lipid-independent and SCAP-independent mechanisms, possibly by general inhibition of ER-to-Golgi transport.

In this paper, the Newmark-Beta algorithm is introduced into the finite-difference time-domain (FDTD) method in dispersion media, resulting in an unconditionally stable method for periodic metallic grating analysis. The proposed method eliminates the Courant-Friedrich-Levy constraint and improves the simulation efficiency for multiscale problems. The dispersion of the metal, which is caused by the evanescent waves propagating along the interface between the metal and dielectric materials in the visible and near-infrared regions, is solved with a generalized auxiliary differential equation (ADE) technique. The extraordinary optical transmission through a periodic metallic grating with different number and different size of the perpendicular bump is also investigated. Compared with the traditional ADE-FDTD method and ADE alternating-direction-implicit FDTD method, the results from the proposed method show its accuracy and efficiency.