Legionella pneumophila Risk from Cooling Tower Systems in China.

Legionella pneumophila widely exists in natural and artificial water environments, which enables it to infect people. L. pneumophila infection causes Legionnaires' disease (LD), which is a significant but relatively uncommon respiratory infection. Approximately 90% of LD is caused by L. pneumophila serogroup 1 (Lp1). Meteorological conditions may affect the infectivity and virulence of Lp1, but the exact relationship between them is still unclear. In this study, we evaluated the virulence of Lp1 by screening of total 156 Lp1 strains isolated from cooling tower water in different regions of China by detecting their abilities to activate NF-κB signaling pathway in vitro. In addition, we screened the distribution of some selected virulence genes in these strains. The virulence, virulence gene distribution, and the meteorological factors were analyzed. We found that both the virulence and the distribution of virulence genes had a certain regional and meteorological correlation. Although the loss of several virulence genes showed significant effects on the virulence of Lp1 strains, the distribution of virulence genes had very limited effects on the virulence of Lp1. IMPORTANCE LD is likely to be underrecognized in many countries. Due to the widespread existence of L. pneumophila in natural and artificial water environments and to the lack of cross-protection against different strains, L. pneumophila is a potentially serious threat to human health. Therefore, effective monitoring of the virulence of L. pneumophila in the water environment is very important to prevent and control the prevalence of LD. Understanding the virulence of L. pneumophila can not only help us to predict the risk of possible outbreaks in advance but can also enable more targeted clinical treatment. This study highlights the importance of understanding the epidemiology and ecology of L. pneumophila isolated from public facilities in terms of public health and biology. Due to the potential for water sources to harbor and disseminate L. pneumophila and to the fact that geographical conditions influence the virulence of L. pneumophila, timely and accurate L. pneumophila virulence surveillance is urgently needed.

Stretchable and conformable variable stiffness device through an electrorheological fluid.

Stiffness variations extend creatures' functions and capabilities to deal with complex environments. In this study, we proposed an electrorheological fluid-based variable stiffness device, named VSERF, made up of soft materials. Our device is soft, thin, and stretchable so that it can conform to surfaces with complex morphologies. The stiffness of the VSERF device can be continuously, independently, and reversibly adjusted by applying an electric field. It achieves 14.8-times compressive stiffness variation and 3.5-times tangential stiffness variation when the electric field intensity increases from 0 V mm-1 to 750 V mm-1. The VSERF device is able to return to its initial shape after removing the external force and electric field, allowing it to be reused. The effects of stretching and bending on the device's capability of stiffness variations are investigated experimentally and the results show that the stiffness variation is unaffected by a stretching strain of up to 20% and a bending curvature of up to 50 m-1. Finally, we show that the VSERF device is capable of conforming to complex surfaces (coral stones, pencils, and 3D printed cubes) in its inactive state, hanging on them with a weight of up to 80 g (19 times of its own weight) in its active state, and detaching when the electric field is removed. The device's short-term and long-term stabilities are experimentally investigated as well. The demonstration of the VSERF's attaching and detaching ability shows that the stiffness-variation device's adaptability to complex environments can be improved.

Gain of circBRAF Represses Glioma Progression by Regulating miR-1290/FBXW7 Axis.

Dysregulated circular RNAs (circRNAs) have been confirmed to partake in the modulation of the glioma progression. Here, we intended to explore the role of circBRAF in glioma and the possible action mechanism. The expression levels of circBRAF, microRNA (miR)-1290 and F-box and WD repeat domain containing 7 (FBXW7) were analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) or western blot. Cell viability was assessed by 3-(4, 5)-dimethylthiazole-2-y1)-2, 5-biphenyl tetrazolium bromide (MTT) assay. Cell cycle distribution was determined by flow cytometry. Cell migration and invasion were evaluated through Trans-well assay. Related protein levels were detected by western blot. Targeted relation among circBRAF, miR-1290 and FBXW7 was validated by dual-luciferase reporter, RNA immunoprecipitation (RIP) and pull-down assays. Xenograft model was constructed to explore the function of circBRAF in vivo. Expression of circBRAF and FBXW7 was decreased in glioma tissues and cells. Upregulation of circBRAF inhibited glioma cell proliferation and metastasis in vitro. MiR-1290 was upregulated in glioma, which was sponged by circBRAF. Besides, circBRAF elevated FBXW7 expression by targeting miR-1290. Introduction of miR-1290 or FBXW7 knockdown could counteract the inhibitory effects of circBRAF upregulation on the malignant phenotypes of glioma cells. Overexpression of circBRAF repressed the tumor growth in vivo. Upregulation of circBRAF suppressed glioma evolvement in vitro and in vivo by regulating miR-1290/FBXW7 axis, broadening the cognition of glioma progression.

Region-Wide Comprehensive Implementation of Roguing Infected Trees, Tree Replacement, and Insecticide Applications Successfully Controls Citrus Huanglongbing.

Huanglongbing (HLB) is a devastating citrus disease worldwide. A three-pronged approach to controlling HLB has been suggested, namely, removal of HLB-symptomatic trees, psyllid control, and replacement with HLB-free trees. However, such a strategy did not lead to successful HLB control in many citrus-producing regions, such as Florida. We hypothesize that this is because of the small-scale or incomprehensive implementation of the program; conversely, a comprehensive implementation of such a strategy at the regional level can successfully control HLB. To test our hypothesis, we investigated the effects of region-wide comprehensive implementation of this scheme to control HLB in Gannan region, China, with a total planted citrus acreage of over 110,000 ha from 2013 to 2019. With the region-wide implementation of comprehensive HLB management, the overall HLB incidence in Gannan decreased from 19.71% in 2014 to 3.86% in 2019. A partial implementation of such a program (without a comprehensive inoculum removal) at the regional level in Brazil resulted in HLB incidence increasing from 1.89% in 2010 to 19.02% in 2019. Using dynamic regression model analyses with data from both Brazil and China, we constructed a model to predict HLB incidence when all three components were applied at 100%. It was predicated that in a region-wide comprehensive implementation of such a program, HLB incidence would be controlled to a level of less than 1%. We conducted economic feasibility analyses and showed that average net profits were positive for groves that implemented the comprehensive strategy, but groves that did not implement it had negative net profits over a 10-year period. Overall, the key for the three-pronged program to successfully control HLB is the large scale (region-wide) and comprehensiveness in implementation. This study provides valuable information to control HLB and other economically important endemic diseases worldwide.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

EDSSA: An Encoder-Decoder Semantic Segmentation Networks Accelerator on OpenCL-Based FPGA Platform.

Visual semantic segmentation, which is represented by the semantic segmentation network, has been widely used in many fields, such as intelligent robots, security, and autonomous driving. However, these Convolutional Neural Network (CNN)-based networks have high requirements for computing resources and programmability for hardware platforms. For embedded platforms and terminal devices in particular, Graphics Processing Unit (GPU)-based computing platforms cannot meet these requirements in terms of size and power consumption. In contrast, the Field Programmable Gate Array (FPGA)-based hardware system not only has flexible programmability and high embeddability, but can also meet lower power consumption requirements, which make it an appropriate solution for semantic segmentation on terminal devices. In this paper, we demonstrate EDSSA-an Encoder-Decoder semantic segmentation networks accelerator architecture which can be implemented with flexible parameter configurations and hardware resources on the FPGA platforms that support Open Computing Language (OpenCL) development. We introduce the related technologies, architecture design, algorithm optimization, and hardware implementation of the Encoder-Decoder semantic segmentation network SegNet as an example, and undertake a performance evaluation. Using an Intel Arria-10 GX1150 platform for evaluation, our work achieves a throughput higher than 432.8 GOP/s with power consumption of about 20 W, which is a 1.2× times improvement the energy-efficiency ratio compared to a high-performance GPU.

Effects of leaf colorness, pigment contents and allelochemicals on the orientation of the Asian citrus psyllid among four Rutaceae host plants.

BACKGROUND: Asian citrus psyllid (ACP) is the primary vector responsible for the transmission of the phloem-limited bacteria Candidatus Liberibacter spp., associated with huanglongbing (HLB), which causes great loss to the citrus industry. Although the roles of leaf color and volatile compounds in the orientation of ACP have been proven, the quantification of color and allelochemicals in the host plant are kept unclear, especially in wild citrus germplasms. RESULTS: Chongyi wild mandarin significantly attracted more ACP than wild Hong Kong kumquat, 'Gannan zao' navel orange and orange jasmine did in the four-choice and olfactometer assays. The color parameters of the tender leaves from Chongyi wild mandarin and 'Gannan zao' were similar. The yellow color in both of them was less saturated than that of the other two plants species, but Chongyi wild mandarin had significant lower carotenoid content (P < 0.05). Notably metabolic profiling differences were observed among the healthy tender shoots from the four tested plants via UPLC-QQQ-MS and GC-MS analyses. Comparing with the other three plant species, 66 and 50 metabolites with significantly different contents in Chongyi wild mandarin were selected as UPLC-identified and GC-identified metabolites of interest (P < 0.05), respectively. Flavonoids accounted for a large group of secondary metabolites of interest, which may function as stimulants or repellents of ACP. Higher content of salicylic acid o-hexoside and lower content of (+)-jasmonic acid in Chongyi wild mandarin may lead to higher amount of methyl salicylate (an ACP attractant) and lower amount of trans-ocimene (an attractant to herbivores' natural enemies) as well as the suppression of JA-mediated wounding response. This kind of synergistic or antagonistic effect among the metabolites differentially accumulated in Chongyi wild mandarin made it a more attractive host plant to ACP. CONCLUSIONS: Less saturated yellow color, high amount of attractants, low amount of repellents and insensitivity of JA-mediated wounding response are the four possible reasons why Chongyi wild mandarin attracted more ACP. This work may shed light on the olfactory and visual response of ACP to wild citrus germplasm hosts, and suggest the feasibility of developing ACP attractants or repellents patterned on potential metabolites.

Anatomy of filamentary threshold switching in amorphous niobium oxide.

The threshold switching behavior of Pt/NbO x /TiN devices is investigated as a function device area and NbO x film thickness and shown to reveal important insight into the structure of the self-assembled switching region. The devices exhibit combined selector-memory (1S1R) behavior after an initial voltage-controlled forming process, but exhibit symmetric threshold switching when the RESET and SET currents are kept below a critical value. In this mode, the threshold and hold voltages are independent of the device area and film thickness but the threshold current (power), while independent of device area, decreases with increasing film thickness. These results are shown to be consistent with a structure in which the threshold switching volume is confined, both laterally and vertically, to the region between the residual memory filament and the TiN electrode, and where the memory filament has a core-shell structure comprising a metallic core and a semiconducting shell. The veracity of this structure is demonstrated by comparing experimental results with the predictions of a simple circuit model, and more detailed finite element simulations. These results provide further insight into the structure and operation of NbO x threshold switching devices that have application in emerging memory and neuromorphic computing fields.

Coupling dynamics of Nb/Nb2O5 relaxation oscillators.

The coupling dynamics of capacitively coupled Nb/Nb2O5 relaxation oscillators are shown to exhibit rich collective behaviour depending on the negative differential resistance response of the individual devices, the operating voltage and the coupling capacitance. These coupled oscillators are shown to exhibit stable frequency and phase locking states at source voltages as low as 2.2 V, with frequency control in the range from 0.85 to 16.2 MHz and frequency tunability of ∼8 MHz V-1. The experimental realisation of such compact, scalable and low power coupled-oscillator systems is of particular significance for the development and implementation of large oscillator networks in non-Boolean computing architectures.

A "click" chemistry constructed affinity system for 2-oxoglutaric acid receptors and binding proteins.

An ingenious and specific affinity resin designed to capture the 2-oxoglutaric acid (2-OG) binding proteins was constructed by appending a 2-OG tag to the solid resin via a Cu-catalyzed Huisgen "click" reaction. The so-obtained affinity resin was able to recognize, retain and separate the established 2-OG binding protein NtcA in both the pure form and crude cellular extract, thus constituting a valuable means of searching for novel 2-OG receptors with a view to exploring the signalling pathways of 2-OG, a key Krebs cycle intermediate with unprecedented signalling functions.

Mimicking the 2-oxoglutaric acid signalling function using molecular probes: insights from structural and functional investigations.

2-Oxoglutaric acid (2-OG) has gained considerable attention because of its newly discovered signalling role in addition to its established metabolic functions. With the aim of further exploring the signalling function of 2-OG, here we present a structure-activity relationship study using 2-OG probes bearing different carbon chain lengths and terminal groups. Our results highlight the importance of the five-membered carbon molecular skeleton and of the two carboxylic terminals in maintaining the signalling functions of the parent molecule 2-OG. These findings provide valuable information for designing new, effective molecular probes able to dissect and discriminate the newly discovered, complex signalling role of 2-OG from its canonical activity in metabolism.

Predictive role of E2F6 in cancer prognosis and responses of immunotherapy.

BACKGROUND: E2F6 is a member of the E2F transcription factor family. Numerous studies have demonstrated that E2F6 is critical to cancer development and progression, but its role in cancer immunotherapy remains unclear. METHODS: Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases were used to obtain RNA-seq data for cancer and normal tissues, and we utilized the cBioPortal to analyze E2F6 genomic alterations in pan-cancer. The protein localization of E2F6 was obtained using the Human Protein Atlas (HPA), and the upregulation of E2F6 expression in clinical glioblastoma multiforme (GBM) tissues was detected by Western blot analysis. The ComPPI website was used to analyze the protein interaction information of E2F6. To evaluate the role of E2F6 in pan-cancer prognosis, we used univariate Cox regression and Kaplan-Meier methods, and gene set enrichment analysis (GSEA) was utilized to identify markers associated with E2F6 expression in tumors. TIMER 2.0 was used to study E2F6-related immune cell infiltration in tumor tissues, and the correlation of E2F6 with immunotherapy biomarkers was investigated using Spearman correlation analysis. The role of E2F6 in the cell cycle was analyzed by flow cytometry, and the Cell Counting Kit-8 (CCK-8) and colony formation assays were utilized to determine the proliferative ability of cells. RESULTS: In most tumor types, E2F6 was highly expressed and was a good predictor of prognosis. E2F6 was significantly related to markers of immune activation, tumor immune cell infiltration, and immune regulators. Furthermore, E2F6 knockdown significantly attenuated the proliferative ability of glioma cells. Finally, E2F6 effectively predicted anti-programmed cell death 1 (PD1) treatment response. CONCLUSION: E2F6 is an effective biomarker that predicts the prognosis of cancer patients treated with anti-immune checkpoint therapy.

Comprehensive analyses of m1A regulator-mediated modification patterns determining prognosis in lower-grade glioma (running title: m1A in LGG).

N1-methyladenosine (m1A) modification is a crucial post-transcriptional regulatory mechanism of messenger RNA (mRNA) in living organisms. Few studies have focused on analysis of m1A regulators in lower-grade gliomas (LGG). We employed the Nonnegative Matrix Factorization (NMF) technique on The Cancer Genome Atlas (TCGA) dataset to categorize LGG patients into 2 groups. These groups exhibited substantial disparities in terms of both overall survival (OS) and levels of infiltrating immune cells. We collected the significantly differentially expressed immune-related genes between the 2 clusters, and performed LASSO regression analysis to obtain m1AScores, and established an m1A-related immune-related gene signature (m1A-RIGS). Next, we categorized all patients with LGG into high- and low-risk subgroups, predictive significance of m1AScore was confirmed by conducting univariate/multivariate Cox regression analyses. Additionally, we confirmed variations in immune-related cells and ssGSEA and among the high-/low-risk subcategories in the TCGA dataset. Finally, our study characterized the effects of MSR1 and BIRC5 on LGG cells utilizing Edu assay and flow cytometry to explore the effects of modulation of these genes on glioma. The results of this study suggested that m1A-RIGS may be an excellent prognostic indicator for patients with LGG, and could also promote development of novel immune-based treatment strategies for LGG. Additionally, BIRC5 and MSR1 may be potential therapeutic targets for LGG.

Engineering electrodeposited ZnO films and their memristive switching performance.

We report the influence of zinc oxide (ZnO) seed layers on the performance of ZnO-based memristive devices fabricated using an electrodeposition approach. The memristive element is based on a sandwich structure using Ag and Pt electrodes. The ZnO seed layer is employed to tune the morphology of the electrodeposited ZnO films in order to increase the grain boundary density as well as construct highly ordered arrangements of grain boundaries. Additionally, the seed layer also assists in optimizing the concentration of oxygen vacancies in the films. The fabricated devices exhibit memristive switching behaviour with symmetrical and asymmetrical hysteresis loops in the absence and presence of ZnO seed layers, respectively. A modest concentration of oxygen vacancy in electrodeposited ZnO films as well as an increase in the ordered arrangement of grain boundaries leads to higher switching ratios in Ag/ZnO/Pt devices.

Design and control of a multi-mobile-robot cooperative transport system based on a novel six degree-of-freedom connector.

Multi-robot cooperative object transport on uneven roads is challenging. The key barrier is dealing with nonholonomic and rigid-formation motion constraints. In this study, to alleviate the influence of these constraints on a multi-robot cooperative transport system (MRCTS), a six degree-of-freedom connector capable of sensing three-axial displacements, three-axial forces, and three-axial angular displacements is designed and employed. Based on the local displacements derived from each connector, we develop a position calibration method to calculate the relative position of each robot and achieve a centralized control strategy. Based on the forces sensed by each connector, we design a decentralized control strategy to accomplish cooperative transport in which a leader robot guides the follower robots toward a destination by applying forces, instead of centralized information broadcasting. The experimental results show that the MRCTS works well on an uneven surface, and the tracking errors are within the design stroke of the connectors, demonstrating the effectiveness of the design and control methods of the MRCTS.

Robotic mobile and mirror milling of large-scale complex structures.

Robotization, miniaturization and portability have become the new development trend of milling equipment for large-scale complex structures, and the robotic mobile and mirror milling technology has reached remarkable progress in practical production.

PneuNet: deep learning for COVID-19 pneumonia diagnosis on chest X-ray image analysis using Vision Transformer.

A long-standing challenge in pneumonia diagnosis is recognizing the pathological lung texture, especially the ground-glass appearance pathological texture. One main difficulty lies in precisely extracting and recognizing the pathological features. The patients, especially those with mild symptoms, show very little difference in lung texture, neither conventional computer vision methods nor convolutional neural networks perform well on pneumonia diagnosis based on chest X-ray (CXR) images. In the meanwhile, the Coronavirus Disease 2019 (COVID-19) pandemic continues wreaking havoc around the world, where quick and accurate diagnosis backed by CXR images is in high demand. Rather than simply recognizing the patterns, extracting feature maps from the original CXR image is what we need in the classification process. Thus, we propose a Vision Transformer (VIT)-based model called PneuNet to make an accurate diagnosis backed by channel-based attention through X-ray images of the lung, where multi-head attention is applied on channel patches rather than feature patches. The techniques presented in this paper are oriented toward the medical application of deep neural networks and VIT. Extensive experiment results show that our method can reach 94.96% accuracy in the three-categories classification problem on the test set, which outperforms previous deep learning models.

Citrus genomic resources unravel putative genetic determinants of Huanglongbing pathogenicity.

Citrus HLB caused by Candidatus Liberibacter asiaticus is a pathogen-triggered immune disease. Here, we identified putative genetic determinants of HLB pathogenicity by integrating citrus genomic resources to characterize the pan-genome of accessions that differ in their response to HLB. Genome-wide association mapping and analysis of allele-specific expression between susceptible, tolerant, and resistant accessions further refined candidates underlying the response to HLB. We first developed a phased diploid assembly of Citrus sinensis 'Newhall' genome and produced resequencing data for 91 citrus accessions that differ in their response to HLB. These data were combined with previous resequencing data from 356 accessions for genome-wide association mapping of the HLB response. Genes determinants for HLB pathogenicity were associated with host immune response, ROS production, and antioxidants. Overall, this study has provided a significant resource of citrus genomic data and identified candidate genes to be further explored to understand the genetic determinants of HLB pathogenicity.

Erratum: Citrus genomic resources unravel putative genetic determinants of Huanglongbing pathogenicity.

[This corrects the article DOI: 10.1016/j.isci.2023.106024.].

Low-power and controllable memory window in Pt/Pr0.7Ca0.3MnO3/yttria-stabilized zirconia/W resistive random-access memory devices.

Yttria-stabilized zirconia (YSZ) layers of various thicknesses were designed and introduced before Pr0.7Ca0.3MnO3 (PCMO) film was deposited on W bottom electrodes with a submicron via-hole structure. By changing the thickness of the YSZ barrier layer (3, 5, 9, and 13 nm), a tunable memory window can be realized while low power consumption (P(max) < 4 microW) is maintained. Resistive switching (RS) in a Pt/PCMO/YSZ/W stack with a thin YSZ layer can be ascribed to an oxidation/reduction reaction caused by a ring-type PCMO/W contact, while RS with a thick YSZ layer may be related to oxygen migration across the YSZ layer between the PCMO film and the W bottom electrode and the increase (decrease) of the effective tunnel barrier height of the YSZ layer. Excellent RS behavior characteristics, such as a large R(HRS)/R(LRS) ratio (> 10(3)), die-to-die uniformity, sweeping endurance, and a retention time of more than 10(3) s, can be obtained by optimizing the thickness of YSZ layer.

The protective effects of dezocine on interleukin-1ß-induced inflammation, oxidative stress and apoptosis of human nucleus pulposus cells and the possible mechanisms.

Intervertebral disc degeneration (IDD) is a natural problem linked to the inflammation. We aimed to investigate the role of dezocine (DEZ) in the development of IDD. Human nucleus pulposus cells (HNPCs) induced by interleukin (IL)-1ß was used as a cellular model of IDD. After treatment with DEZ, HNPCs viability was evaluated with a CCK-8 assay. Then, the levels of inflammatory factors, including IL-6 and tumor necrosis factor-α (TNF-α), and oxidative stress-related markers, including reactive oxygen species (ROS), malondialdehyde (MDA) and reduced glutathione (GSH), were tested by RT-qPCR or kits. TUNEL staining was employed to detect cell apoptosis and Western blot was used to determine the expression of proteins related to inflammation, oxidative stress, apoptosis, endoplasmic reticulum stress (ERS) and MAPK signaling. Afterward, PMA, a MAPK signaling pathway agonist, was adopted for exploring the regulatory effects of DEZ on MAPK pathway. Results indicated that DEZ enhanced cell viability of HNPCs after IL-1ß exposure. DEZ alleviated the inflammation and oxidative stress, evidenced by decreased levels of IL-6, TNF-α, ROS, MDA, p-NF-κB p65, NF-κB p65 in nucleus, cox-2 and increased levels of NF-κB p65 in cytoplasm, GSH, SOD1 and SOD2. Moreover, DEZ notably inhibited IL-1ß-induced apoptosis of HNPCs. Furthermore, DEZ suppressed the levels of ERS-related proteins. The levels of related proteins in MAPK signaling including p-P38 and p-ERK1/2 were remarkably reduced after DEZ administration. By contrast, PMA crippled the impacts of DEZ on inflammation, oxidative stress and apoptosis of HNPCs induced by IL-1ß. Collectively, DEZ ameliorates IL-1ß-induced HNPCs injury via inhibiting MAPK signaling.