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Abstract Objectives we performed this meta- analysis to investigate the impact of insulin receptor substrate 1 (IRS1) gene rs1801278 on susceptibility to gestational diabetes mellitus (GDM). Methods The pooled odds ratio (OR) and 95% confidence interval (95% CI) were calculated, and p value is used to determine statistical significance. Sensitivity analysis was performed under three models (dominant, recessive and allele model), and the pooled ORs and 95%CI were calculated. Funnel plots and Begger’s regression test were employed to test the publication bias. Results The meta-analysis included 4777 participants (2116 cases and 2661 controls). The IRS1 rs1801278 (C/T) were not significant associated with GDM risk under the dominant and allele models, OR (95%CI) = 1.22 (0.88–1.70) and 1.24 (0.91–1.68), respectively (both p values were more than 0.05). But we also found the IRS1 rs1801278 (C/T) were significant associated with GDM risk under the recessive model, OR (95%CI) = 0.37 (0.16–0.86), p = 0.030. Our results showed that none of the studies affected the quality of the pooled OR. We also found no significant publication bias existed in this meta study for three genetic models, P TT + CT vs. CC = 0.445; P CC+CT vs. TT= 0.095; P C vs. T = 0.697. Conclusion this meta-analysis indicated that IRS1 rs1801278 (C/T) was associated with the GDM risk under the recessive model but was not associated with the GDM risk under dominant and allele models.

Abstract Background Viral diseases are posing threat to annual production and quality of tobacco in China. Recently, tomato spotted wilt orthotospovirus (TSWV) has been reported to infect three major crops including tobacco. Current study was aimed to investigate the population dynamics and molecular diversity of the TSWV. In the current study, to assess and identify the prevalence and evolutionary history of TSWV in tobacco crops in China, full-length genome sequences of TSWV isolates from tobacco, were identified and analyzed. Methods After trimming and validation, sequences of new isolates were submitted to GenBank. We identified the full-length genomes of ten TSWV isolates, infecting tobacco plants from various regions of China. Besides these, six isolates were partially sequenced. Phylogenetic analysis was performed to assess the relativeness of newly identified sequences and corresponding sequences from GenBank. Recombination and population dynamics analysis was performed using RDP4, RAT, and statistical estimation. Reassortment analysis was performed using MegaX software. Results Phylogenetic analysis of 41 newly identified sequences, depicted that the majority of the Chinese isolates have separate placement in the tree. RDP4 software predicted that RNA M of newly reported isolate YNKM-2 had a recombinant region spanning from 3111 to 3811 bp. The indication of parental sequences (YNKMXD and YNHHKY) from newly identified isolates, revealed the conservation of local TSWV population. Genetic diversity and population dynamics analysis also support the same trend. RNA M was highlighted to be more capable of mutating or evolving as revealed by data obtained from RDP4, RAT, population dynamics, and phylogenetic analyses. Reassortment analysis revealed that it might have happened in L segment of TSWV isolate YNKMXD (reported herein). Conclusion Taken together, this is the first detailed study revealing the pattern of TWSV genetic diversity, and population dynamics helping to better understand the ability of this pathogen to drastically reduce the tobacco production in China. Also, this is a valuable addition to the existing worldwide profile of TSWV, especially in China, where a few studies related to TSWV have been reported including only one complete genome of this virus isolated from tobacco plants.

Abstract Background Viral diseases continue to pose a major threat to the world’s commercial crops. The in-depth exploration and efficient utilization of resistance proteins have become crucial strategies for their control. However, current delivery methods for introducing foreign DNA suffer from host range limitations, low transformation efficiencies, tissue damage, or unavoidable DNA integration into the host genome. The nanocarriers provides a convenient channel for the DNA delivery and functional utilization of disease-resistant proteins. Results In this research, we identified a cysteine-rich venom protein (NbCRVP) in Nicotiana benthamiana for the first time. Virus-induced gene silencing and transient overexpression clarified that NbCRVP could inhibit the infection of tobacco mosaic virus, potato virus Y, and cucumber mosaic virus, making it a broad-spectrum antiviral protein. Yeast two-hybrid assay, co-immunoprecipitation, and bimolecular fluorescence complementation revealed that calcium-dependent lipid-binding (CaLB domain) family protein (NbCalB) interacted with NbCRVP to assist NbCRVP playing a stronger antiviral effect. Here, we demonstrated for the first time the efficient co-delivery of DNA expressing NbCRVP and NbCalB into plants using poly(amidoamine) (PAMAM) nanocarriers, achieving stronger broad-spectrum antiviral effects. Conclusions Our work presents a tool for species-independent transfer of two interacting protein DNA into plant cells in a specific ratio for enhanced antiviral effect without transgenic integration, which further demonstrated new strategies for nanocarrier-mediated DNA delivery of disease-resistant proteins. Graphical abstract

Abstract Diatoms are dominant marine algae and contribute around a quarter of global primary productivity, the success of which is largely attributed to their photosynthetic capacity aided by specific fucoxanthin chlorophyll-binding proteins (FCPs) to enhance the blue-green light absorption under water. We purified a photosystem II (PSII)-FCPII supercomplex and a trimeric FCP from Cyclotella meneghiniana (Cm) and solved their structures by cryo-electron microscopy (cryo-EM). The structures reveal detailed organizations of monomeric, dimeric and trimeric FCP antennae, as well as distinct assemblies of Lhcx6_1 and dimeric FCPII-H in PSII core. Each Cm-PSII-FCPII monomer contains an Lhcx6_1, an FCP heterodimer and other three FCP monomers, which form an efficient pigment network for harvesting energy. More diadinoxanthins and diatoxanthins are found in FCPs, which may function to quench excess energy. The trimeric FCP contains more chlorophylls c and fucoxanthins. These diversified FCPs and PSII-FCPII provide a structural basis for efficient light energy harvesting, transfer, and dissipation in C. meneghiniana.

Potato virus Y (PVY) disease is a global problem that causes significant damage to crop quality and yield. As traditional chemical control methods are ineffective against PVY, it is crucial to explore new control strategies. MicroRNAs (miRNAs) play a crucial role in plant and animal defense responses to biotic and abiotic stresses. These endogenous miRNAs act as a link between antiviral gene pathways and host immunity. Several miRNAs target plant immune genes and are involved in the virus infection process. In this study, we conducted small RNA sequencing and transcriptome sequencing on healthy and PVY-infected N. benthamiana tissues (roots, stems, and leaves). Through bioinformatics analysis, we predicted potential targets of differentially expressed miRNAs using the N. benthamiana reference genome and the PVY genome. We then compared the identified differentially expressed mRNAs with the predicted target genes to uncover the complex relationships between miRNAs and their targets. This study successfully constructed a miRNA-mRNA network through the joint analysis of Small RNA sequencing and transcriptome sequencing, which unveiled potential miRNA targets and identified potential binding sites of miRNAs on the PVY genome. This miRNA-mRNA regulatory network suggests the involvement of miRNAs in the virus infection process.

Specific detection of cellular superoxide is challenging. Here, the authors designed 1,2,4,5-tetrazine based fluorogenic probes for specific and sensitive imaging of superoxide, and applied them in high throughput screening of modulators of oxidative stress.

Abstract. The coronavirus disease 2019 (COVID-19) pandemic poses a great threat to public health. Individuals who are immunocompromised because of the progression of the primary disease or receiving immunosuppressive medications are prone to severe COVID-19 complications and poor outcomes. Abundant data have shown that many COVID-19 vaccines are safe and effective in large-scale populations; however, these clinical trials have excluded immunocompromised populations. Available evidence indicates that immunocompromised populations have a blunted immune response to other vaccines, raising concerns regarding the efficacy of COVID-19 vaccination in these populations. Thus, there is an urgent need to delineate the efficacy of COVID-19 vaccines in these vulnerable populations. Here, we review the characteristics of specific humoral and cellular responses to COVID-19 vaccination in immunocompromised populations, including HIV-infected patients and those receiving immunosuppressive treatment, especially solid organ transplant recipients and those undergoing anti-CD20 treatment. We also addressed the challenges that immunocompromised populations will face in the future pandemic and the need for basic and clinical translational studies to highlight the best vaccination strategies for these populations.

Abstract Background Lysine 2-hydroxyisobutyrylation (Khib) is a novel and conserved post-translational modification (PTM). Frankliniella occidentalis are economically important agricultural pests globally and also notorious for vectoring destructive plant viruses. To better study the disease transmission mechanism of F. occidentalis, it is necessary to conduct in-depth analysis of it. So far, no Khib modification of insects has been reported. Results In this study, a proteome-wide analysis of Khib modifications in F. occidentalis was analyzed for the first time through the combination of high performance liquid chromatography fractionation technology and 2-hydroxyisobutyrylated peptide enrichment and other advanced technologies, 4093 Khib sites were identified on 1125 modified proteins. Bioinformatics and functional enrichment analyses showed that Khib-modified proteins were significantly enriched in many cell compartments and pathways, especially related to various cellular components and biological processes, and were more concentrated in ribosomes and proteasome subunits, involved in energy metabolism, protein synthesis and degradation, compared to the other nine species including Japonica rice, Homo sapiens, P. patens, Botrytis, Ustilaginoidea virens, Saccharomyces cerevisiae, T. gondii, C. albicans, and F. oxysporum. And Khib sites on virus-interacting insect proteins were discovered for the first time, such as cyclophilin and endoCP-GN. Conclusions After three repeated experiments, we found a total of 4093 Khib sites on 1125 proteins. These modified proteins are mainly concentrated in ribosomes and proteasome subunits, and are widely involved in a variety of critical biological activities and metabolic processes of F. occidentalis. In addition, for the first time, Khib modification sites are found on the proteome of F. occidentalis, and these sites could be acted as for the virus interaction, including cyclophilin and endoCP-GN. The global map of 2-hydroxyisobutyrylation in thrips is an invaluable resource to better understand the biological processes of thrips and provide new means for disease control and mitigation of pest damage to crops.

Nanoparticles (NPs) derived from RNA interference (RNAi) are considered a potentially revolutionary technique in the field of plant protection in the future. However, the application of NPs in RNAi is hindered by the conflict between the high cost of RNA production and the large quantity of materials required for field application. This study aimed to evaluate the antiviral efficacy of commercially available nanomaterials, such as chitosan quaternary ammonium salt (CQAS), amine functionalized silica nano powder (ASNP), and carbon quantum dots (CQD), that carried double-stranded RNA (dsRNA) via various delivery methods, including infiltration, spraying, and root soaking. ASNP-dsRNA NPs are recommended for root soaking, which is considered the most effective method of antiviral compound application. The most effective antiviral compound tested was CQAS-dsRNA NPs delivered by root soaking. Using fluorescence, FITC-CQAS-dsCP-Cy3, and CQD-dsCP-Cy3 NPs demonstrated the uptake and transport pathways of dsRNA NPs in plants when applied to plants in different modes. The duration of protection with NPs applied in various modes was then compared, providing references for evaluating the retention period of various types of NPs. All three types of NPs effectively silenced genes in plants and afforded at least 14 days of protection against viral infection. Particularly, CQD-dsRNA NPs could protect systemic leaves for 21 days following spraying.

Summary The potato virus Y (PVY) is a plant virus that causes massive crop losses globally, especially in Solanaceae crops. A strain of the plant growth‐promoting rhizobacterium (PGPR), Serratia marcescens‐S3 was found to inhibit PVY replication in Nicotiana benthamiana. However, there have been no in‐depth studies demonstrating the underlying mechanism. In the current study, we found that ubiquitination of NbHsc70‐2 is an important way for Serratia marcescens‐S3 to trigger induced systemic resistance (ISR). After the treatment with S. marcescens‐S3, the protein level of NbHsc70‐2 reduced significantly. Inhibiting of ubiquitination increased the accumulation of NbHsc70‐2 in plants and reduced S. marcescens‐S3‐mediated resistance to PVY. Furthermore, transgenic engineered Nicotiana benthamiana NbHsc70‐2KO and NbHsc70‐2USM were constructed using CRISPR‐Cas9‐mediated NbHsc70‐2 knock‐out and ubiquitination respectively. S. marcescens‐S3 significantly reduced the inhibition of NbHsc70‐2 protein accumulation in NbHsc70‐2KO and NbHsc70‐2USM. The virulence of PVY was stronger in NbHsc70‐2USM than the wild‐type plants. These results showed that S. marcescens‐S3 increases the ubiquitination of NbHsc70‐2 to inhibit the recruitment of molecular chaperone NbHsc70‐2 to reduce its replication and infection of PVY.

Power electronic equipment to miniaturization, high integration direction while facing the problem of high heat flow density and uneven temperature distribution. The large temperature fluctuations and uneven temperature distribution in the operation of power electronic equipment will lead to thermal stress, and excessive thermal stress or uneven distribution will cause fatigue failure of the packaging material, resulting in reduced reliability, module failure, and reduced life of power electronic equipment. In this paper, we propose two kinds of liquid-cooled flow channel non-linear reinforced heat transfer homogeneous liquid-cooled plate, which is theoretically derived to achieve the design requirement of uniform temperature on the heating side wall surface. The thermal design of the cold plate is carried out using ANSYS Workbench, and the indicators of various structures of the cold plate are analyzed and compared in terms of their ability to dissipate heat and maintain temperature uniformity. Based on the original runner structure, the heat dissipation performance of the rod structure and fin structure was evaluated, and the form of the internal heat dissipation structure of the runner was determined. The results show that the integrated liquid cooling plate temperature uniformity and flow resistance of both factors, the fin column heat sink is significantly better than the cylindrical fin column heat sink in the case of the same thermal resistance, the fin column heat sink flow resistance is significantly lower than the cylindrical fin column heat sink.

Background: RNA-editing refers to post-transcriptional transcript alterations that lead to the formation of protein isoforms and the progression of various tumors. However, little is known about its roles in gliomas.Aim: The aim of this study is to identify prognosis-related RNA-editing sites (PREs) in glioma, and to explore their specific effects on glioma and potential mechanisms of action.Methods: Glioma genomic and clinical data were obtained from TCGA database and SYNAPSE platform. The PREs was identified with regression analyses and the corresponding prognostic model was evaluated with survival analysis and receiver operating characteristic curve. Functional enrichment of differentially expressed genes between risk groups was performed to explore action mechanisms. The CIBERSORT, ssGSEA, gene set variation analysis, and ESTIMATE algorithms were employed to assess the association between PREs risk score and variations of tumor microenvironment, immune cell infiltration, immune checkpoints, and immune responses. The maftools and pRRophetic packages were used to evaluate tumor mutation burden and predict drug sensitivity.Results: A total of thirty-five RNA-editing sites were identified as prognosis-related in glioma. Functional enrichment implied variation of immune-related pathways between groups. Notably, glioma samples with higher PREs risk score exhibited higher immune score, lower tumor purity, increased infiltration of macrophage and regulatory T cells, suppressed NK cell activation, elevated immune function score, upregulated immune checkpoint gene expression, and higher tumor mutation burden, all of which implied worse response to immune therapy. Finally, high-risk glioma samples are more sensitive to Z-LLNle-CHO and temozolomide, while the low-risk ones respond better to Lisitinib.Conclusion: We identified a PREs signature of thirty-five RNA editing sites and calculated their corresponding risk coefficients. Higher total signature risk score indicates worse prognosis and worse immune response and lower sensitivity to immune therapy. The novel PREs signature could help risk stratification, immunotherapy response prediction, individualized treatment strategy-making for glioma patients, and development of novel therapeutic approaches.

With the continuous progress of automotive new energy technology, the motor has become an important part of the power system, and the heat dissipation of insulated-gate bipolar transistors (IGBT) determines the reliability of the power system. Minichannel structure can be added to the thermal management system of new energy vehicles to improve the heat transfer capacity. Due to the growth of the boundary layer in the smooth minichannel flow channel, the cooling performance improvement was limited. Pin-fins and rib structures were used to break the boundary layer and increased the heat transfer area to enhance the heat transfer capacity. In this study, a numerical simulation model of minichannel with triangular pin-fins with different rotation angles was established and calculated using the SST k-omega method. The temperature field, velocity field, pressure, and vortex distribution under different configurations were discussed in detail. The jet area formed by the prism wall and the side wall of the minichannel would impact the wall and reduce the growth of the boundary layer. However, the stagnation area generated in the center and corner will reduce the improvement of heat transfer capacity. The thermo-hydraulic characteristics of different configurations at different Reynolds numbers (Re), such as Nusselt number (Nu), Darcy friction resistance coefficient (f), and performance evaluation criterion (PEC), were analyzed. As Re increased, the best and worst configurations changed, the best configuration changed from the 90°–120° structure to the 120°–120° structure, and the worst configuration changed from the 75°–60° to the 60°–60° structure. When the Re = 663, the influence of the front and rear rotation angle on the cooling performance was explored. When the rotation angle was closer to 60°, the cooling performance of the minichannel was better. And the closer the rotation angle was to 120°, the cooling performance was better. This has a reference effect on the design of minichannel heat sinks.

Stereopsis is the ability of human beings to get the 3D perception on real scenarios. The conventional stereopsis measurement is based on subjective judgment for stereograms, leading to be easily affected by personal consciousness. To alleviate the issue, in this paper, the EEG signals evoked by dynamic random dot stereograms (DRDS) are collected for stereogram recognition, which can help the ophthalmologists diagnose strabismus patients even without real-time communication. To classify the collected Electroencephalography (EEG) signals, a novel multi-scale temporal self-attention and dynamical graph convolution hybrid network (MTS-DGCHN) is proposed, including multi-scale temporal self-attention module, dynamical graph convolution module and classification module. Firstly, the multi-scale temporal self-attention module is employed to learn time continuity information, where the temporal self-attention block is designed to highlight the global importance of each time segments in one EEG trial, and the multi-scale convolution block is developed to further extract advanced temporal features in multiple receptive fields. Meanwhile, the dynamical graph convolution module is utilized to capture spatial functional relationships between different EEG electrodes, in which the adjacency matrix of each GCN layer is adaptively tuned to explore the optimal intrinsic relationship. Finally, the temporal and spatial features are fed into the classification module to obtain prediction results. Extensive experiments are conducted on collected datasets i.e., SRDA and SRDB, and the results demonstrate the proposed MTS-DGCHN achieves outstanding classification performance compared with the other methods. The datasets are available at https://github.com/YANGeeg/TJU-SRD-datasets and the code is at https://github.com/YANGeeg/MTS-DGCHN.

Abstract Background The annual economic loss caused by plant viruses exceeds 10 billion dollars due to the lack of ideal control measures. Quercetin is a flavonol compound that exerts a control effect on plant virus diseases, but its poor solubility and stability limit the control efficiency. Fortunately, the development of nanopesticides has led to new ideas. Results In this study, 117 nm quercetin nanoliposomes with excellent stability were prepared from biomaterials, and few surfactants and stabilizers were added to optimize the formula. Nbhsp70er-1 and Nbhsp70c-A were found to be the target genes of quercetin, through abiotic and biotic stress, and the nanoliposomes improved the inhibitory effect at the gene and protein levels by 33.6 and 42%, respectively. Finally, the results of field experiment showed that the control efficiency was 38% higher than that of the conventional quercetin formulation and higher than those of other antiviral agents. Conclusion This research innovatively reports the combination of biological antiviral agents and nanotechnology to control plant virus diseases, and it significantly improved the control efficiency and reduced the use of traditional chemical pesticides. Graphical Abstract

Western flower thrips (Frankliniella occidentalis) are among the most important pests globally that transmit destructive plant viruses and infest multiple commercial crops. Lysine lactylation (Klac) is a recently discovered novel post-translational modification (PTM). We used liquid chromatography-mass spectrometry to identify the global lactylated proteome of F. occidentalis, and further enriched the identified lactylated proteins using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). In the present study, we identified 1,458 Klac sites in 469 proteins from F. occidentalis. Bioinformatics analysis showed that Klac was widely distributed in F. occidentalis proteins, and these Klac modified proteins participated in multiple biological processes. GO and KEGG enrichment analysis revealed that Klac proteins were significantly enriched in multiple cellular compartments and metabolic pathways, such as the ribosome and carbon metabolism pathways. Two Klac proteins were found to be involved in the regulation of the TSWV (Tomato spotted wilt virus) transmission in F. occidentalis. This study provides a systematic report and a rich dataset of lactylation in F. occidentalis proteome for potential studies on the Klac protein of this notorious pest.

Bufotenines, a natural component from toad venom, showed great potential for development as a novel anti-inflammation and analgesia agent, but the potential toxicity limited its clinic use. In this paper, bufotenines-loaded liposome was prepared and optimized. Then, the therapeutic effects and drug safety of bufotenines-liposome were investigated against inflammation and pain on animal models, with a focus on gastrointestinal toxicity. Bufotenines and its liposome significantly increased paw withdrawal mechanical threshold (PWMT) in Von Frey test and hot paw withdrawal latency (HPWL) in hot-plate test. Moreover, intestinal absorption in vitro and pathological analysis in vivo showed that total bufotenines-loaded liposome significantly reduced the gastrointestinal irritation through reducing exposure of total bufotenines on intestinal tissue. High-sensitivity lipidomics analysis revealed the effect of total bufotenines-loaded liposome were be related to the down-regulation of inflammatory mediators from cyclooxygenase (COX) and lipoxygenase (LOX), the up-regulation of cytochrome P450 (CYP450), and other pathways, thus regulating lipid metabolism pathway and ultimately reducing gastrointestinal irritation. This study shows that liposome-loaded bufotenines has anti-inflammatory, analgesic effects and achieves toxicity reduction. These results provide systematic evidences for efficacy and safety of toad venom active ingredients.

The properties and distributions of precipitation are often determined by specific synoptic patterns. Hence, the objective identification of corresponding impact patterns is an important field of research for improving rain forecasting. However, the identification of the weather patterns producing intense rainfall is much more challenging. Since they are violent and local, impact patterns tend to be meso- or smaller-scale systems and are often incompletely presented or only presented in limited regions. In this paper, a deep learning network with a feature cross-fusion module, FConvNeXt, was proposed to address this difficulty and showed great potential. Four major patterns corresponding to intense rainfall in the Beijing–Tianjing–Hebei Region were studied. Statistical testing showed that FConvNeXt performed better than ConvNeXt and ResNet and that the model could identify the weak synoptic forcing type, the subtropical high-pressure type, and the low-vortex pattern with high accuracy. Furthermore, a strictly independent 2021 dataset was tested, and FConvNeXt maintained an equal if not even slightly better performance in spite of a decrease in the subtropical high-pressure type. Meanwhile, the study showed that the accuracy in identifying the upper-level trough type is the lowest for the three deep learning methods, which may be because the northeast vortex was intercepted in the limited region, making it difficult to distinguish from the shallow upper-level trough type. This study is useful for improving the fine objective of forecasting intense rainfall.

In recent years, tumor classification based on the gene expression omnibus has become a continuous attention field in the area of bioinformatics. Integration machine learning techniques are an efficient methods to solve these problems. Generally, in order to obtain good performance in the supervised learning tasks, a large number of labelled samples will be required. However, in many cases, only a few labelled samples and abundant unlabelled samples exist in the training database. The process of labelling these unlabelled samples manually is difficult and expensive. Therefore, semi-supervised learning approaches have been proposed to utilize unlabelled samples to improve the performance of a model. However, noisy samples decrease the robustness of model in semi-supervised learning. We wish training style that samples can be implemented to train by from high- to low-confidence, self-training can meet this requirement, and the deep forest approach with the hyper-parameter settings used in this work can obtain good accuracy. Therefore, in this paper, we present a novel semi-supervised learning approach with a deep forest model to increase the performance of tumor classification, which employs unlabelled samples and minimizes the cost; that is, a updated unlabelled sample mechanism is investigated to expand the number of high-confidence pseudo-labelled samples. Multiple real-world experiments indicate that our proposed approach can obtain results up 0.96 accuracy and F1-Score, and 0.9798 AUCs.

The ubiquitin–proteasome system (UPS) plays an important role in virus–host interactions. However, the mechanism by which the UPS is involved in innate immunity remains unclear. In this study, we identified a novel major latex protein-like protein 43 (NbMLP43) that conferred resistance to Nicotiana benthamiana against potato virus Y (PVY) infection. PVY infection strongly induced NbMLP43 transcription but decreased NbMLP43 at the protein level. We verified that B-box zinc finger protein 24 (NbBBX24) interacted directly with NbMLP43 and that NbBBX24, a light responsive factor, acted as an essential intermediate component targeting NbMLP43 for its ubiquitination and degradation via the UPS. PVY, tobacco mosaic virus, (TMV) and cucumber mosaic virus (CMV) infections could promote NbMLP43 ubiquitination and proteasomal degradation to enhance viral infection. Ubiquitination occurred at lysine 38 (K38) within NbMLP43, and non-ubiquitinated NbMLP43(K38R) conferred stronger resistance to RNA viruses. Overall, our results indicate that the novel NbMLP43 protein is a target of the UPS in the competition between defense and viral anti-defense and enriches existing theoretical studies on the use of UPS by viruses to promote infection.

Abstract Background Toremifene (TOR) is a selective oestrogen receptor modulator (SERM) and has comparable efficacy to that of tamoxifen (TAM) in breast cancer patients. Herein, we compared the safety of TOR to that of TAM in the adjuvant treatment of premenopausal breast cancer. Methods This was a prospective randomized and open-label clinical study. Premenopausal patients with hormonal receptor (HR)-positive early breast cancer were randomly assigned (1:1) to receive TOR) or TAM treatment. The follow-up period was 1 year. The primary end point was the incidence of ovarian cysts, and secondary end points were the incidence of endometrial thickening, changes in female hormones, the incidence of fatty liver, changes in the modified Kupperman index (mKMI) and changes in quality of life. Results There were 92 patients in the final analysis. The incidences of ovarian cysts were 42.6% in the TOR group and 51.1% in the TAM group (p = 0.441). Forty-one patients (87.2%) in the TOR group and 36 patients (80.0%) in the TAM group experienced endometrial thickening (p = 0.348). The proportions of patients with fatty liver were 31.9% in the TOR group and 26.7% in the TAM group (p = 0.581). No significant differences in the mKMI or quality of life were observed between the two groups. Conclusions TOR and TAM have similar side effects on the female genital system and quality of life in premenopausal early breast cancer patients. Trial registration ClinicalTrials.gov NCT02344940. Registered 26 January 2015 (retrospectively registered).

Abstract Background Major latex proteins (MLPs) belong to the MLP subfamily in Bet v 1 protein family and respond to both biotic and abiotic stresses, which play critical roles in plant disease resistance. As the type species of widely distributed and economically devastating Potyvirus, Potato virus Y (PVY) is one of the major constraints to important crop plants including tobacco (Nicotiana benthamiana) worldwide. Despite the great losses owing to PVY infection in tobacco, there is no previous study investigating the potential role of MLPs in developing resistance to viral infection. Results In this study, for the first time we have identified and functionally analyzed the MLP-like protein 28 from N. benthamiana, denoted as NbMLP28 and investigated its role in conferring resistance to N. benthamiana against PVY infection. NbMLP28 was localized to the plasmalemma and nucleus, with the highest level in the root. NbMLP28 gene was hypothesized to be triggered by PVY infection and was highly expressed in jasmonic acid (JA) signaling pathway. Further validation was achieved through silencing of NbMLP28 through virus-induced gene silencing (VIGS) that rendered N. benthamiana plants more vulnerable to PVY infection, contrary to overexpression that enhanced resistance. Conclusions Taken together, this is the first study describing the role of NbMLP28 in tobacco against PVY infection and provide a pivotal point towards obtaining pathogen-resistant tobacco varieties through constructing new candidate genes of MLP subfamily.

One of the challenges in emotion recognition is finding an effective way to represent spatial-temporal features from EEG. To fully utilize the features on multiple dimensions of EEG signals, we propose a parallel sequence-channel projection convolutional neural network, including temporal stream sub-network, spatial stream sub-network, and fusion classification block. Temporal stream extracts temporal continuity via sequence-projection layer while spatial stream captures spatial correlation via channel-projection layer. Both sequence-projection and channel-projection adopt length-synchronized convolutional kernel to decode whole time and space information. The size of length-synchronized convolutional kernel is equal to the length of transmitted EEG sequence. The fusion classification block combines the extracted temporal and spatial features into a joint spatial-temporal feature vector for emotion prediction. In addition, we present a baseline noise filtering module to amplify input signals and a random channels exchange strategy to enrich the baseline-removed emotional signals. Experimental evaluation on DEAP dataset reveals that the proposed method achieves state-of-the-art classification performance for the binary classification task. The recognition accuracies reach to 96.16% and 95.89% for valence and arousal. The proposed method can improve 3% to 6% than other latest advanced works.

Abstract Circular RNAs (circRNAs) have been increasingly revealed to be desirable biomarkers for some tumors, including hepatocellular carcinoma (HCC). Combined with our previous microarray screening results, we aimed to determine the hsa_circ_0028502 and hsa_circ_0076251 expression features in HCC, analyze the relationship between their expression level and clinical and pathological characteristics, and investigate their diagnostic and prognostic values. Our data demonstrated that the hsa_circ_0028502 and hsa_circ_0076251 levels were considerably lower in HCC tissues than in adjacent paracancerous tissues (P

Objective: 1,3-Dioleoyl-2-palmitoylglycerol (OPO) is an ideal structured triglyceride for infant formula, with a similar structure to human milk fat. We conducted this randomized, double-blind controlled, single-center trial to evaluate the effects of an OPO formula in infants.Study Design: One hundred seventy-four healthy term infants

As one of the top 10 plant viruses, the severity of losses to crop productivity caused by the tomato spotted wilt virus (TSWV) has resulted in an urgent need to develop a more sensitive and rapid method of detection. In this study, we developed a CRISPR/Cas13a-based detection system to diagnose TSWV in tomato and western flower thrips (Frankliniella occidentalis). The detection system relies on recombinase polymerase amplification and Cas13a-mediated collateral cleavage activity. Positive results can be distinguished after 20 min by a significantly enhanced fluorescence signal. We tested the sensitivity of CRISPR/Cas13a-based detection system and found that the detection system that we developed has limits of detection that reaches 2.26 × 102 copies/μl and a 10-fold increase compared with the sensitivity of using RT-PCR to detect the virus. Furthermore, the CRISPR/Cas13a-based detection system has a high selectivity for the TSWV without interference from other viruses. The CRISPR/Cas13a-based detection system was utilized to detect the TSWV in samples of tomato leaves and the transmission vector F. occidentalis that were fully consistent with the results when RT-PCR was used to detect the virus.

Inflammation is a primary defense and immune response. However, under pathological conditions, the inflammation processes always become uncontrolled and lead to chronic diseases. Bufotenine, as a natural component from toad venom, showed great potential for development as a novel anti-inflammation and analgesia agent. This study aimed to investigate the therapeutic effects of bufotenine against inflammation and pain on animal models with a focus on lipid metabolism. In pharmacological studies, bufotenine significantly inhibited the swelling rates on formalin-induced paw edema model, and increased paw withdrawal mechanical thresholds (PWMTs) in von Frey test and thermal pain thresholds (TPTs) in hot-plate test. High-sensitivity lipidomics analysis revealed the effects might be related to the down-regulation of inflammatory mediators from cyclooxygenase (COX), lipoxygenase (LOX), cytochrome P450 (CYP450), linoleic acid (LA), docosahexaenoic acid (DHA) and other pathways. The activities might result from the binding of bufotenine and its receptors, including sigma-1 receptor and 5-Hydroxytryptamine receptor 3A, thus regulating lipid metabolism pathway. The research provided a systemic evidence for the actions and mechanism of bufotenine. It suggested that the natural compound might be a potential candidate for reducing inflammatory pain disorders.

Abstract Background Previous studies have demonstrated that left-sided tumors have better prognoses than right-sided tumors in RAS wild-type mCRC (metastatic colorectal cancer) patients, while anti-EGFR mAbs appear to have no advantage compared with bevacizumab for right-sided tumors in these patients. Nevertheless, it remains unclear whether primary tumor location affects patients’ options for potentially curative resection. Methods PubMed, the Cochrane Library, Embase, ASCO, and ESMO conference abstracts were searched. The inclusion criteria were RCT (randomized controlled trials) studies that evaluated the efficacy of anti-EGFR mAbs based on primary tumor location. The outcomes included ORR, ETS, and DpR. ORs for ORR were calculated with 95% confidence intervals by Comprehensive Meta-Analysis, version 2.0. Result Nine studies including nine RCTs were analyzed. Regardless of left- or right-sided tumors, the ORRs for anti-EGFR mAb (left-sided: 80.2%, 95% CI, 47–95%; I 2 = 76.9%; right-sided: 46.1%, 95% CI, 39.4–53.0%; I 2 = 18.9%) were both higher than the control arm including chemotherapy with or without bevacizumab. The ORs for anti-EGFR mAbs have a significant benefit compared with chemotherapy with or without bevacizumab in left-sided tumors (OR = 2.19, 95% CI, 1.41–3.38; P

In this study, schorl was used as an effective adsorbent for ciprofloxacin removal from wastewater. The adsorption performance, mechanism and effect of metal ion on sorption were investigated. Adsorption capacity reached a maximum (8.49 mg/g) when the pH value was 5.5. The pseudo-second-order kinetic model and Freundlich model could better describe the experimental data. The negative ΔH (–22.96 KJ/mol) value showed that the adsorption process was exothermic. The results also indicated physical adsorption existed on the adsorption process, which was in agreement with the analysis of X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy. The desorption rate could reach 94%, which suggested that schorl had a good desorption and regeneration performance. Coexisting ions, such as Cu2+ and Al3+, could obviously inhibit adsorption, and the inhibition from Al3+ was significantly higher than that from Cu2+. However, the additional Zn2+ could slightly promote the adsorption.

Chitinase 3-like protein 1(CHI3L1) participates in physiological and pathophysiological process, such as cell survival, cell proliferation, tissue remodeling, angiogenesis, etc. Some studies demonstrated that CHI3L1 is liver-enriched and has better application value in staging liver fibrosis than platelet ratio index(APRI) and fibrosis-4 index(FIB-4) and that CHI3L1 can be used in monitoring the prognosis of hepatocellular carcinoma (HCC). In this review, we summarized the pathophysiological role and the diagnostic value of CHI3L1 in liver fibrosis in different background and HCC.

Abstract Histone crotonylation is a new lysine acylation type of post-translational modification (PTM) enriched at active gene promoters and potential enhancers in yeast and mammalian cells. However, lysine crotonylation in nonhistone proteins and plant cells has not yet been studied. In the present study, we performed a global crotonylation proteome analysis of Nicotiana tabacum (tobacco) using high-resolution LC-MS/MS coupled with highly sensitive immune-affinity purification. A total of 2044 lysine modification sites distributed on 637 proteins were identified, representing the most abundant lysine acylation proteome reported in the plant kingdom. Similar to lysine acetylation and succinylation in plants, lysine crotonylation was related to multiple metabolism pathways, such as carbon metabolism, the citrate cycle, glycolysis, and the biosynthesis of amino acids. Importantly, 72 proteins participated in multiple processes of photosynthesis, and most of the enzymes involved in chlorophyll synthesis were modified through crotonylation. Numerous crotonylated proteins were implicated in the biosynthesis, folding, and degradation of proteins through the ubiquitin-proteasome system. Several crotonylated proteins related to chromatin organization are also discussed here. These data represent the first report of a global crotonylation proteome and provide a promising starting point for further functional research of crotonylation in nonhistone proteins.

The orphan nuclear receptor (NR5A2), which belongs to the NR5A subfamily of nuclear receptors, is expressed in developing and adult tissues of endodermal origin, and can contribute to the development of several cancers through regulating cell proliferation. NR5A2 (rs3790843 and rs3790844) single nucleotide polymorphisms (SNPs) genotyping were examined in DNA samples, extracted from paraffin-embedded cancer tissue. Clinicopathologic and follow-up data were collected from 944 patients with gastric cancer (GC). Associations of the 2 SNPs with the progression and prognosis in gastric cancer patients were analyzed using the SPSS version 18.0. We found that NR5A2 rs3790843 polymorphism was significantly associated with the risk of GC which had regional lymph node metastasis (p = 0.044) or distant metastasis (p = 0.020). Our results also indicated that rs3790844 polymorphism was associated with the increased overall survival (OS) of GC patients in the dominant model (GG vs. GA/AA, HR (hazard ratio) = 0.823, 95% CI (confidence interval) = 0.679–0.997), suggesting a potential protective role of the variant A allele. Additionally, in the stratified analysis, both NR5A2 rs3790843 and rs3790844 polymorphism were associated with significantly lower risk of death in the groups of female, tumor size >5 cm in a dominant model. Our results represent the first demonstration that the NR5A2 rs3790844 polymorphism is associated with increased OS of GC patients in the dominant model, and similar results were found among the female group and tumor size >5 cm group for NR5A2 rs3790843 polymorphism. Further validation in other larger studies with different ethnic populations and functional evaluations are needed.

This study aimed to investigate the association between POU class5 homeobox 1 pseudogene 1 gene (POU5F1P1) rs10505477 polymorphism and the prognosis of Chinese gastric cancer patients, who received cisplatin-based chemotherapy after surgical resection. POU5F1P1 rs10505477 was genotyped using the SNaPshot method in 944 gastric cancer patients who received gastrectomy. The association of rs10505477 G > A polymorphism with the progression and prognosis in gastric cancer patients was statistically analyzed using the SPSS version 18.0 for Windows. The results reveal that rs10505477 polymorphism has a negatively effect on the overall survival of gastric cancer patients in cisplatin-based chemotherapy subgroup (HR = 1.764, 95% CI = 1.069–2.911, p = 0.023). Our preliminary study indicates for the first time that POU5F1P1 rs10505477 is correlated with survival of gastric cancer patients who receving cisplatin-based chemotherapy after gastrectomy. Further studies are warranted to investigate the mechanism and to verify our results in different populations.

Global navigation satellite system (GNSS) integer ambiguity acceptance test is one of the open problems in GNSS data processing. A number of ambiguity acceptance tests have been proposed from different perspectives and then unified into the integer aperture estimation framework. The existing comparative studies indicate that the impact of test statistics form on the test performance is less critical, while how to construct an efficient, practical test threshold is still challenging. Based on the likelihood ratio test theory, a new computationally efficient ambiguity acceptance test with controllable success fix rate, namely the fixed likelihood ratio (FL-) approach is proposed, which does not require Monte Carlo simulation. The study indicates that the fixed failure rate (FF-) approach can only control the overall failure rate of the acceptance region, but the local failure rate is not controllable. The proposed FL-approach only accepts the fixed solution meeting the likelihood ratio requirement. With properly chosen likelihood ratio threshold, the FL-approach achieves comparable success rate as the FF-approach and even lower failure rate than the FF-approach for the strong underlying model cases. The fixed success fix rate of the FL-approach is verified with both simulation data and real GNSS data. The numerical results indicate that the success fix rate of the FL-approach achieves >98% while the failure rate is

The presence of None-line-of-sight (NLOS) is one of the major challenging issues in time of arrival (TOA) based source localization, especially for the sparse anchor scenarios. Sparse anchors can reduce the system deployment cost, so this has become increasingly popular in the source location. However, fewer anchors bring new challenges to ensure localization precision and reliability, especially in NLOS environments. The maximum likelihood (ML) estimation is the most popular location estimator for its simplicity and efficiency, while it becomes extremely difficult to reliably identify the NLOS measurements when the redundant observations are not enough. In this study, we proposed an NLOS detection algorithm called misclosure check (MC) to overcome this issue, which intends to provide a more reliable location in the sparse anchor environment. The MC algorithm checks the misclosure of different triangles and then obtains the possible NLOS from these misclosures. By forming multiple misclosure conditions, the MC algorithm can identify NLOS measurements reliably, even in a sparse anchor environment. The performance of the MC algorithm is evaluated in a typical sparse anchor environment and the results indicate that the MC algorithm achieves promising NLOS identification capacity without abundant redundant measurements. The real data test also confirmed that the MC algorithm achieves better position precision than other three robust location estimators in an NLOS environment since it can correctly identify more NLOS measurements.

In Global navigation satellite system (GNSS) data processing, integer ambiguity acceptance test is considered as a challenging problem. A number of ambiguity acceptance tests have been proposed from different perspective and then unified into the integer aperture estimation (IA) framework. Among all the IA estimators, the optimal integer aperture (OIA) achieves the highest success rate with the fixed failure rate tolerance. However, the OIA is of less practical appealing due to its high computation complexity. On the other hand, the popular discrimination tests employ only two integer candidates, which are the essential reason for their sub-optimality. In this study, a generalized difference test (GDT) is proposed to exploit the benefit of including three or more integer candidates to improve their performance from theoretical perspective. The simulation results indicate that the third best integer candidates contribute to more than 70% success rate improvement for integer bootstrapping success rate higher than 0.8 case. Therefore, the GDT with three integer candidates (GDT3) achieves a good trade-off between the performance and computation burden. The threshold function is also applied for rapid determination of the fixed failure rate (FF)-threshold for GDT3. The performance improvement of GDT3 is validated with real GNSS data set. The numerical results indicate that GDT3 achieves higher empirical success rate while the empirical failure rate remains comparable. In a 20 km baseline test, the success rate GDT3 increase 7% with almost the same empirical failure rate.

The network real-time kinematic (RTK) technique can provide centimeter-level real time positioning solutions and play a key role in geo-spatial infrastructure. With ever-increasing popularity, network RTK systems will face issues in the support of large numbers of concurrent users. In the past, high-precision positioning services were oriented towards professionals and only supported a few concurrent users. Currently, precise positioning provides a spatial foundation for artificial intelligence (AI), and countless smart devices (autonomous cars, unmanned aerial-vehicles (UAVs), robotic equipment, etc.) require precise positioning services. Therefore, the development of approaches to support large-scale network RTK systems is urgent. In this study, we proposed a self-organizing spatial clustering (SOSC) approach which automatically clusters online users to reduce the computational load on the network RTK system server side. The experimental results indicate that both the SOSC algorithm and the grid algorithm can reduce the computational load efficiently, while the SOSC algorithm gives a more elastic and adaptive clustering solution with different datasets. The SOSC algorithm determines the cluster number and the mean distance to cluster center (MDTCC) according to the data set, while the grid approaches are all predefined. The side-effects of clustering algorithms on the user side are analyzed with real global navigation satellite system (GNSS) data sets. The experimental results indicate that 10 km can be safely used as the cluster radius threshold for the SOSC algorithm without significantly reducing the positioning precision and reliability on the user side.

OBJECTIVES: Genome-wide association studies (GWAS) have demonstrated that the single nucleotide polymorphism (SNP) MAP3K1 rs889312 is a genetic susceptibility marker significantly associated with a risk of hormone-related tumors such as breast cancer. Considering steroid hormone-mediated signaling pathways have an important role in the progression of gastric cancer, we hypothesized that MAP3K1 rs889312 may be associated with survival outcomes in gastric cancer. The purpose of this study was to test this hypothesis. METHODS: We genotyped MAP3K1 rs889312 using TaqMan in 884 gastric cancer patients who received subtotal or total gastrectomy. Kaplan-Meier survival analysis and Cox proportional hazard regression were used to analyze the association between MAP3K1 rs889312 genotypes and survival outcomes of gastric cancer. RESULTS: Our findings reveal that the rs889312 heterozygous AC genotype was significantly associated with an increased rate of mortality among patients with diffuse-type gastric cancer (log-rank P = 0.028 for AC versus AA/CC, hazard ratio [HR] = 1.32, 95% confidence interval [CI] = 1.03-1.69), compared to those carrying the homozygous variant genotypes (AA/CC). Additionally, univariate and multivariate Cox regression analysis demonstrate that rs889312 polymorphism was an independent risk factor for poor survival in these patients. CONCLUSIONS: In conclusion, we demonstrate that MAP3K1 rs889312 is closely correlated with outcome among diffuse-type gastric cancer. This raises the possibility for rs889312 polymorphisms to be used as an independent indicator for predicting the prognosis of diffuse-type gastric cancer within the Chinese population.