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In view of the influence of aliasing noise on the effectiveness and accuracy of bearing fault diagnosis, a bearing fault diagnosis algorithm based on the spatial decoupling method of modified kernel principal component analysis (MKPCA) and the residual network with deformable convolution (DC‐ResNet) is innovatively proposed. Firstly, the Gaussian noise with different signal‐to‐noise ratios (SNRs) is added to the data to simulate the different degrees of noise in the actual data acquisition process. The MKPCA is used to project the fault signal with different SNRs in the kernel space to reduce the data dimension and eliminate some noise effects. Finally, the DC‐ResNet model is used to further filter the noise effects and fully extract the fault features through the training of the preprocessed data. The proposed algorithm is tested on the Case Western Reserve University (CWRU) and Xi'an Jiaotong University and Changxing Sumyoung Technology Co., Ltd. (XJTU‐SY) bearing data sets with different SNR noise. The fault diagnosis accuracy can reach 100% within 30 min, which has better performance than most of the existing methods. The experimental results show that the algorithm has an excellent effect on accuracy and computation complexity under different noise levels. [ABSTRACT FROM AUTHOR]

Background: The expression of long non‐coding RNA (lncRNA) prostate cancer‐associated ncRNA transcripts 1 (PCAT1) is increased in non‐small cell lung cancer (NSCLC). It stimulates tumour growth and metastasis, but its role in the radioimmune responses remain unknown. We aimed to explore the impacts of PCAT1 on tumorigenesis and radioimmune responses and the underlying molecular mechanisms in NSCLC. Methods: Comprehensive bioinformatics analysis was performed to identify immunosuppressive lncRNAs involved with tumour invasion in NSCLC. The expression levels of PCAT1 were analysed by in situ hybridisation in 55 paired NSCLC tissues and adjacent normal tissues. Both loss‐ and gain‐of‐function assays were performed to examine the effects of PCAT1 and SOX2 on NSCLC cell behaviours in vivo and in vitro. Bioinformatic analyses, chromatin isolation by RNA purification (ChIRP) and dual‐luciferase reporter assays were applied to validate the regulatory effects of PCAT1 on SOX2 expression. Chromatin immunoprecipitation, luciferase and rescue assays were utilised to identify the relationship between SOX2 and the cGAS/stimulator of interferon genes (STING) signalling. Results: PCAT1 was immunosuppressive and related with NSCLC invasion. Increased PCAT1 was negatively correlated with immune cell infiltration in NSCLC. PCAT1 knockdown restrained proliferation, increased apoptosis, and repressed cell metastasis in vivo and in vitro. PCAT1 activated SOX2 that accelerated tumorigenesis and immunosuppression. SOX2 promoted tumour growth through inhibiting cytotoxic T‐cell immunity. Moreover, SOX2 restrained cGAS transcription and hampered downstream type I interferon (IFN)‐induced immune responses. Inhibition of PCAT1/SOX2 in collaboration with radiation further inhibited tumour growth, and initiated the cGAS/STING signalling pathway, which enhanced the immune responses of radiotherapy in NSCLC. Conclusions: PCAT1/SOX2 axis promoted tumorigenesis and immunosuppression through inhibition of cGAS/STING signalling‐mediated T‐cell activation. Inhibition of PCAT1 and SOX2 synergised with radiotherapy to activate the immune response and could serve as potential therapeutic targets. [ABSTRACT FROM AUTHOR]

In the 21st century, stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is still the most devastating disease of wheat globally. Despite the critical roles of the alternate host plants, the Berberis species, in the sexual reproduction and spread of Pst, the climate change impacts on the redistribution of Berberis plants, and their potential risk of incurring wheat stripe rust are scarcely discussed in the literature. This study evaluated the potential risk of Pst in wheat cultivation in Sichuan Province, China, for the first time, by analyzing the dynamics of Berberis plants and the change in Pst oversummering range under climate change scenarios. Ensembles of small models (ESMs) in combination with four algorithms were used to project the future (i.e., 2041–2060, 2061–2080, and 2081–2100) distributions of 54 Berberis species in Sichuan Province based on two shared socioeconomic pathways (SSP) scenarios. The species richness of Berberis was predicted to increase in northwestern Sichuan but decreased in southern and eastern Sichuan under both SSP245 and SSP585 scenarios. The mean temperature of the driest quarter was found to be the determinant of the distributional shifts for the majority of Berberis plants. Our overlapping assessments indicated that the risk of wheat stripe rust would be reduced in southwestern Sichuan. In contrast, it would be aggravated in the northwest due to the predicted shifts of Berberis plants northwards and stronger shrinkage of Pst oversummering range occurring in the south than in the north. In the "hotspots" of the stripe rust pathogen, risk assessment in advance could provide a scientific basis for decision‐makers and local communities in effectively controlling wheat stripe rust, thus further sustaining food security through adapting to future climate change. [ABSTRACT FROM AUTHOR]

Lung adenocarcinoma (LUAD) is the most common and lethal cancer worldwide. Radiotherapy (RT) is widely used at all stages of LUAD, and the development of immunotherapy substantially enhances the survival of LUAD patients. Although the emerging treatments for LUAD have improved prognosis, only a small fraction of patients can benefit from clinical therapies. Thereby, approaches assessing responses to RT and immunotherapy in LUAD patients are essential. After integrating the analysis of RT, immunization, mRNA, and clinical information, we constructed a signature based on 308 tumor‐infiltrating B lymphocyte‐specific genes (TILBSig) using a machine learning method. TILBSig was composed of 6 B cell‐specific genes (PARP15, BIRC3, RUBCNL, SP110, TLE1, and FADS3), which were highly associated with the overall survival as independent factors. TILBSig was able to differentiate better survival compared with worse survival among different patients, and served as an independent factor for clinical characteristics. The low‐risk TILBSig group was correlated with more immune cell infiltration (especially B lineages) and lower cancer stem cell characteristics than the high‐risk group. The patients with lower risk scores were more likely to respond to RT and immunotherapy. TILBSig served as an excellent predicator for prognosis and response to immunotherapy and RT in LUAD patients. [ABSTRACT FROM AUTHOR]

Deciphering protein‐protein interactions (PPIs) is fundamental for understanding signal transduction pathways in plants. The split firefly luciferase (Fluc) complementation (SLC) assay has been widely used for analyzing PPIs. However, concern has risen about the bulky halves of Fluc interfering with the functions of their fusion partners. Nano luciferase (Nluc) is the smallest substitute for Fluc with improved stability and luminescence. Here, we developed a dual‐use system enabling the detection of PPIs through the Nluc‐based SLC and co‐immunoprecipitation assays. This was realized by coexpression of two proteins under investigation in fusion with the HA‐ or FLAG‐tagged Nluc halves, respectively. We validated the robustness of this system by reproducing multiple previously documented PPIs in protoplasts or Agrobacterium‐transformed plants. We next applied this system to evaluate the homodimerization of Arabidopsis CERK1, a coreceptor of fungal elicitor chitin, and its heterodimerization with other homologs in the absence or presence of chitin. Moreover, split fragments of Nluc were fused to two cytosolic ends of Arabidopsis calcium channels CNGC2 and CNGC4 to help sense the allosteric change induced by the bacterial elicitor flg22. Collectively, these results demonstrate the usefulness of the Nluc‐based SLC assay for probing constitutive or inducible PPIs and protein allostery in plant cells. [ABSTRACT FROM AUTHOR]

Legionella pneumophila encodes an extracellular secreted phospholipase A named PlaA that is translocated by the type II secretion system. It plays an essential role in maintaining the integrity of Legionella‐containing vacuoles in L. pneumophila pathogenesis. Here, it is shown that PlaA has a main lysophospholipase activity to hydrolyze fatty‐acyl groups in lysophospholipids. Although it has a very low phospholipase A activity to catalyze the hydrolysis of fatty‐acyl groups in phospholipids, PlaA can bind phospholipids such as 1,2‐dipalmitoylphosphatidylcholine with a dissociation constant of 11.1 µM. Sequence‐alignment analysis combined with activity assays revealed that PlaA contains a distinct substrate‐binding site among the known structures of the phospholipase A family, implying that PlaA may present a novel mechanism for substrate recognition. Native PlaA and its selenomethionine (SeMet)‐substituted form were purified and crystallized by vapour diffusion in hanging drops at 296 K. Diffraction data were collected to a resolution of 2.0 Å for native PlaA protein and to a resolution of 2.7 Å for SeMet‐substituted PlaA protein. The crystals of native PlaA belonged to the monoclinic space group P21, while the crystals of SeMet‐substituted PlaA belonged to the primitive orthorhombic space group P212121. Initial phases for PlaA were obtained from SeMet SAD data sets. [ABSTRACT FROM AUTHOR]

Purpose: Several molecular epidemiology studies have evidenced an association of environmental factors and genetic polymorphisms with breast cancer (BC) risk. However, most have considered the functions of a single element rather than combined effects. Methods: This case‐control study of 693 newly‐diagnosed BC cases and 714 cancer‐free controls evaluated the effect of multiple exposures to environmental factors and polymorphisms in CYP27B1 and IL‐13 on BC risk. Genotypes were detected using TaqMan genotyping. Combinations and interactions were analyzed using cross‐over analysis and multivariate logistic regression. Combining exposure models were assessed using classification and regression tree and multivariate logistic regression analyses. Results: No significant independent association was observed for any polymorphism in CYP27B1 or IL‐13 with the risk of BC. However, significant combined effects were noted for ≥1 time/wk physical activity with rs10877012 (adjusted odds ratio [ORadj] = 0.21, 95% confidence interval [CI] = 0.11‐0.39) and rs4646536 (ORadj = 0.21, 95% CI = 0.11‐0.39) in CYP27B1. Furthermore, taking garlic ≥4 times/wk, ≥1 time/wk physical activity, and a psychological index score ≥33 all displayed significant combined effects with three IL‐13 polymorphisms. These relationships remained significant after Bonferroni correction for multiple comparisons. Combining exposure models indicated that compared with consuming garlic ≥4 times/wk, five models (model 5, ORadj = 2.94, 95% CI = 1.07‐8.06; model 6, ORadj = 10.26, 95% CI = 5.81‐18.10; model 7, ORadj = 5.05, 95% CI = 2.78‐9.17; model 8, ORadj = 3.95, 95% CI = 2.79‐5.58; and model 9, ORadj = 7.97, 95% CI = 5.26‐12.07) showed a significant increased risk. Conclusions: Our findings suggest that personalized adjustments to diet and behavioral patterns may aid BC prevention in variant carriers of CYP27B1 and IL‐13. [ABSTRACT FROM AUTHOR]

Introduction: There has been a rapid increase in the number of influenza and invasive pulmonary aspergillosis (IPA) co‐infection. Objectives: To explore the risk factors and predictors of a poor prognosis in influenza and IPA co‐infection. Methods: We included patients with confirmed influenza during the 2017‐2018 influenza season and cases of influenza and IPA co‐infection in the literature. Results: A total of 64 patients with influenza infection were admitted to ICU. Of these patients, 18 were co‐infected with IPA. Others were assigned to the control group (n = 46). A total of 45 patients from the literature were added to the IPA group (n = 63). A multivariate logistic regression suggested that influenza patients who were given steroids after ICU admission, who had a white blood count (WBC) of more than 10*109/L on ICU admission and whose CT findings manifested as multiple nodules and cavities might have a higher risk of developing IPA. Compared to survivors, non‐survivors had higher sequential organ failure assessment (SOFA) scores (16 ± 4 points vs 8 ± 4 points, P < 0.001), lower CD4+ T cell counts on ICU admission [315 (83‐466) cells/μL vs 152 (50‐220) cells/μL, P = 0.031] and more requirement extracorporeal membrane oxygenation (ECMO) support [13 (50%) vs 7 (18.9%), P = 0.015]. Conclusions: Influenza patients who are given steroids after ICU admission, who have WBCs of greater than 10*109/L on ICU admission, and whose CT imaging shows multiple nodules and cavities might have a high risk of IPA. Higher SOFA scores, CD4+ T cell counts lower than 200 cells/μL on ICU admission and more ECMO requirement might be predictors of a poor prognosis. [ABSTRACT FROM AUTHOR]

The Legionella pneumophila type II secretion system can promote bacterial growth under a wide variety of conditions and mediates the secretion of more than 25 proteins, including the uncharacterized effector Lpg2622. Here, we determined the crystal structures of apo‐Lpg2622 and Lpg2622 in complex with the cysteine protease inhibitor E64. Structural analysis suggests that Lpg2622 belongs to the C1 family peptidases. Interestingly, unlike the other structurally resolved papain‐like cysteine proteases, the propeptide of Lpg2622 forms a novel super‐secondary structural fold (hairpin‐turn‐helix) and can be categorized into a new group. In addition, the N‐terminal β‐sheet of the Lpg2622 propeptide plays a regulatory role on enzymatic activity. This study enhances our understanding of the classification and regulatory mechanisms of the C1 family peptidases. [ABSTRACT FROM AUTHOR]

Abstract: Liver injury and dysregulated glucose homoeostasis are common manifestations during sepsis. Although plenty of studies reported insulin could protect against multiple organ injuries caused by critical infections among patients, little was known about the precise mechanism. We investigated whether liver inflammatory pathway and central neuropeptides were involved in the process. In sepsis rats, hepatic IKK/NF‐κB pathway and STAT3 were strongly activated, along with reduced body weight, blood glucose and suppressed hepatic gluconeogenesis (GNG). Peripheral insulin administration efficiently attenuated liver dysfunction and glucose metabolic disorders by suppressing hypothalamic anorexigenic neuropeptide proopiomelanocortin (POMC) expression, hepatic NF‐κB pathway and STAT3 phosphorylation. Furthermore, knockdown of hypothalamic POMC significantly diminished protective effect of insulin on hepatic GNG and insulin‐induced STAT3 inactivation, but not inflammation or IKK/NF‐κB pathway. These results suggest that hepatic IKK/NF‐κB pathway mediates the anti‐inflammatory effect of insulin in septic rats, and peripheral insulin treatment may improve hepatic GNG by inhibiting STAT3 phosphorylation dependent on hypothalamic POMC expression. [ABSTRACT FROM AUTHOR]

VirK family [Pfam06903] consists of 14 bacterial VirK proteins of around 145 residues in length. The function of this family is unknown. Herein, using single-wavelength anomalous diffraction, we determined the crystal structure of lpg1832, a VirK family protein from Legionella pneumophila, at 2.0 Å resolution. This is the first structural determination of a VirK domain-containing protein. Lpg1832 is a type II secretion system-dependent extracellular protein that folds into a novel barrel-shaped structure. It is found to adopt a quaternary assembly comprising a homotetramer. The three-dimensional structure of lpg1832 provides the first structural information pertaining to the VirK family and allows us to possibly identify its functionally important regions. [ABSTRACT FROM AUTHOR]

Lpg0406, a hypothetical protein from Legionella pneumophila, belongs to carboxymuconolactone decarboxylase (CMD) family. We determined the crystal structure of lpg0406 both in its apo and reduced form. The structures reveal that lpg0406 forms a hexamer and have disulfide exchange properties. The protein has an all-helical fold with a conserved thioredoxin-like active site CXXC motif and a proton relay system similar to that of alkylhydroperoxidase from Mycobacterium tuberculosis (MtAhpD), suggesting that lpg0406 might function as an enzyme with peroxidase activity and involved in antioxidant defense. A comparison of the size and the surface topology of the putative substrate-binding region between lpg0406 and MtAhpD indicates that the two enzymes accommodate the different substrate preferences. The structural findings will enhance understanding of the CMD family protein structure and its various functions. [ABSTRACT FROM AUTHOR]

The major acid phosphatase from Legionella pneumophila ( LpMAP) belongs to the histidine acid phosphatase superfamily. It contains the characteristic histidine acid phosphatase (HAP) sequence motif RHG XR XP responsible for the hydrolysis of a phosphoryl group from phosphate monoesters under acidic conditions. Here, the crystallization and preliminary X-ray analysis of crystals of LpMAP in the apo form and in complex with L-(+)-tartrate are described. By using the hanging-drop vapour-diffusion method, apo LpMAP and LpMAP-tartrate were crystallized in space group P21, with unit-cell parameters a = 91.50, b = 56.48, c = 146.35 Å, β = 110.01°, and in space group P1, with unit-cell parameters a = 55.51, b = 73.51 , c = 98.78 Å, α = 78.82, β = 77.65, γ = 67.73°, respectively. Diffraction data were collected at 100 K and the phases were determined using the molecular-replacement method. [ABSTRACT FROM AUTHOR]

Gene therapy shows promising application in cancer therapy, but the lack of an ideal gene delivery system is still a tough challenge for cancer gene therapy. Previously, we prepared a novel cationic nanogel, heparin-polyethylenimine (HPEI), which had potential application in gene delivery. In the present study, we constructed a plasmid with high expression efficiency of interleukin-15 (IL15) and investigated the effects HPEI-plasmid IL15 (HPEI-pIL15) complexes on the distribution level of the lung. We then evaluated the anticancer effect of HPEI-pIL15 complexes on lung metastases of B16-F10 melanoma and CT26 colon carcinoma. These results demonstrated that intravenous injection of the HPEI-pIL15 complex exhibited the highest plasmid distribution level in the lung compared with that of PEI2K-pIL15 and PEI25K-pIL15, and mice treated with HPEI-pIL15 had a lower tumor metastasis index compared with other treatment groups. Moreover, the number of natural killer cells, which were intermingled among the tumor cells, and the level of tumor necrosis factor-α and interferon-γ in the serum also increased in the pIL15-treated mice. Furthermore, the cytotoxic activity of spleen cells also increased significantly in the HPEI-pIL15 group. In addition, induction of apoptosis and inhibition of cell proliferation in lung tumor foci in the HPEI-pIL15 group was observed. Taken together, treating lung metastasis cancer with the HPEI nanogels delivered by plasmid IL15 might be a new and interesting cancer gene therapy protocol. ( Cancer Sci 2011; 102: 1403-1409) [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is one of the histological types of primary liver cancer with high recurrence and mortality in the world. The purpose of this study was to explore the diagnostic and therapeutic value for HCC patients. Methods: In this study, we investigated the circulating miR‐130b‐5p (miR‐130b) and miR‐21‐5p (miR‐21) expression levels in patients with HCC and their association with clinical parameters. Results: The circulating miR‐130b and miR‐21 were all upregulated in patients with HCC. The upregulated microRNAs (miRNAs) were associated with clinicopathological parameters of tumor capsular infiltration and clinical TNM stage. Also, the poor prognosis of patients with upregulated miRNAs levels suggested that it may be an effective therapeutic target for HCC by suppression of the miRNAs levels. In addition, the combined detection of serum miR‐130b and miR‐21 performed better in the diagnosis of HCC with a sensitivity of 92.16% and an accuracy rate of 77.51%. In vivo, tumors treated with the nanoparticle (NP)/miR‐130b and miR‐21 inhibitor complexes had significantly lower growth than the other groups. Conclusion: The circulating miR‐130b and miR‐21 can be used as potential tumor biomarkers to diagnose liver cancer, and the combined detection of serum miR‐130b and miR‐21 is superior to the diagnosis of HCC. NP/miR‐130b and miR‐21 inhibitor complexes show good therapeutic effects in vivo and are expected to become therapeutic targets worthy of further study. [ABSTRACT FROM AUTHOR]