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As an emerging visual task, vehicle re-identification refers to the identification of the same vehicle across multiple cameras. Herein, we propose a novel vehicle re-identification method that uses an improved ResNet-50 architecture and utilizes the topology information of a surveillance network to rerank the final results. In the training stage, we apply several data augmentation approaches to expand our training data and increase their diversity in a cost-effective manner. We reform the original RestNet-50 architecture by adding non-local blocks to implement the attention mechanism and replacing part of the batch normalization operations with instance batch normalization. After obtaining preliminary results from the proposed model, we use the reranking algorithm, whose core function is to improve the similarity scores of all images on the most likely path that the vehicle tends to appear to optimize the final results. Compared with most existing state-of-the-art methods, our method is lighter, requires less data annotation, and offers competitive performance.

Radiation therapy (RT) in combination with an immune checkpoint inhibitor (ICI) represents a promising regimen for non-small cell lung cancer (NSCLC); however, the underlying mechanisms are poorly characterized. We identified a specific dose of RT that conferred tumor regression and improved survival in NSCLC models when combined with ICIs. The immune-modulating functions of RT were ascribed to activated lung-resident Scgb1a1+ club cells. Notably, mice with club-cell-specific knockout of synaptosome-associated protein 23 failed to benefit from the combination treatment, indicating a pivotal role of club cell secretome. We identified eight club cell secretory proteins that inhibited immunosuppressive myeloid cells, reduced pro-tumor inflammation and enhanced antitumor immunity. Notably, CC10, a member of club cell secretome, was increased in plasma of patients with NSCLC responding to the combination therapy. By revealing an immunoregulatory role of club cells, our studies have the potential to guide future clinical trials of ICIs in NSCLC. Mittal and colleagues investigate the mechanisms underlying the therapeutic effects of radiation therapy in combination with checkpoint blockade, finding a role for activated lung-resident secretory club cells in modulating antitumor immune responses.

Enterovirus 71 (EV71) is the major pathogens of human hand, foot, and mouth disease (HFMD). EV71 efficiently escapes innate immunity responses of the host to cause infection. At present, no effective antiviral drugs for EV71 are available. Anemoside B4 (B4) is a natural saponin isolated from the roots of Pulsatilla chinensis (Bunge) Regel. P. chinensis extracts that shows a wide variety of biological activities. In this study, we investigated the antiviral activities of B4 against EV71 both in cell culture and in suckling mice. We showed that B4 (12.5–200 μM) dose dependently increased the viability of EV71-infected RD cells with an IC(50) value of 24.95 ± 0.05 μM against EV71. The antiviral activity of B4 was associated with enhanced interferon (IFN)-β response, since knockdown of IFN-β abolished its antiviral activity. We also confirmed that the enhanced IFN response was mediated via activation of retinoic acid-inducible gene I (RIG-I) like receptors (RLRs) pathway, and it was executed by upregulation of 14-3-3 protein, which disrupted the interaction between yes-associated protein (YAP) and interferon regulatory factor 3 (IRF3). By using amino acids in cell culture (SILAC)-based proteomics profiling, we identified the Hippo pathway as the top-ranking functional cluster in B4-treated EV71-infected cells. In vivo experiments were conducted in suckling mice (2-day-old) infected with EV71 and subsequently B4 (200 mg · kg(−1) · d(−1), i.p.) was administered for 16 days. We showed that B4 administration effectively suppressed EV71 replication and improved muscle inflammation and limb activity. Meanwhile, B4 administration regulated the expressions of HFMD biomarkers IL-10 and IFN-γ, attenuating complications of EV71 infection. Collectively, our results suggest that B4 could enhance the antiviral effect of IFN-β by orchestrating Hippo and RLRs pathway, and B4 would be a potential lead compound for developing an anti-EV71 drug.

α-Terpineol, terpinen-4-ol, and δ-terpineol, isomers of terpineol, are among the compounds that give Cinnamomum longepaniculatum leaf oil its distinguished pleasant smell. The objective of this study was to evaluate the antimicrobial activity of these three isomeric terpineols. The determination of antibacterial activity was based on the minimum inhibition concentration (MIC) and minimum bactericide concentration (MBC). Changes in time-kill curve, alkaline phosphatase (AKP), UV-absorbing material, membrane potential, and scanning electron microscopy (SEM) were measured to elucidate the possible antimicrobial mechanism. α-Terpineol, terpinen-4-ol, and δ-terpineol demonstrated good inhibitory effects against several gram-negative bacteria, particularly Shigella flexneri. MIC and MBC of α-terpineol and terpinen-4-ol were similar (0.766 mg/mL and 1.531 mg/mL, respectively) for S. flexneri, while the MIC and MBC values of δ-terpineol were 0.780 mg/mL and 3.125 mg/mL, respectively. Time-kill curves showed that the antibacterial activities of the tested compounds were in a concentration-dependent manner. Release of nucleic acids and proteins along with a decrease in membrane potential proved that α-terpineol, terpinen-4-ol, and δ-terpineol could increase the membrane permeability of Shigella flexneri. Additionally, the release of AKP suggested that the cell wall was destroyed. SEM analysis further confirmed that S. flexneri cell membranes were damaged by α-terpineol, terpinen-4-ol, and δ-terpineol. Our research suggests that these three isomeric terpineols have the potential of being used as natural antibacterial agents by destroying the cell membrane and wall, resulting in cell death. However, the specific antibacterial activity differences need further investigation.

Background Insulin positively correlates with the length of the eye axis and is increased in the vitreous and serum of patients with pathological myopia (PM). How insulin influences the physiological process of retinal pigment epithelial (RPE) cells in PM remains unclear. This study aimed to explore the effect of insulin on the ultrastructure and function of RPE cells and the role of PI3K/AKT/mTOR signaling involved in the development of PM. Methods The ARPE-19 cells were treated with different concentrations of insulin to analyze the cell morphology, cell viability, the protein level of insulin receptor β, and the mRNA and protein levels of and PM-related factors (TIMP-2, MMP-2, bFGF, and IGF-1). The ultrastructure of APRE-19 cells was also observed after insulin treatment. Besides, the PI3K/AKT/mTOR signaling was studied with or without the PI3K inhibitor LY294002 in ARPE-19 cells. Results Insulin enhanced the cell viability of ARPE-19 cells and caused the endoplasmic reticulum to expand and vesiculate, suggesting increased secretion of growth factors and degeneration in ARPE-19 cells. Furthermore, the insulin receptor β was stimulated with insulin treatment, subsequently, the phosphorylation of AKT and mTOR was positively activated, which was adversely suppressed in the presence of LY294002. The secretion of TIMP-2 and bFGF was significantly decreased, and the secretion of MMP-2 and IGF-1 was highly elevated with insulin treatment depending on the concentration in ARPE-19 cells. Furthermore, the effect of insulin on PM-related proteins was restored with the addition of LY294002. Conclusions Our results indicated that insulin regulated the secretion of PM-related factors via the PI3K/AKT/mTOR signaling pathway in retinal pigment epithelial cells, and thus probably promoted the development of PM through transducing regulation signals from retina to choroid and sclera.

The logarithmic law of mean temperature profile has been observed in different regions in Rayleigh-B\'enard turbulence. However, how thermal plumes correlate to the log law of temperature and how the velocity profile changes with pressure gradient are not fully understood. Here, we performed three-dimensional simulations of Rayleigh-B\'enard turbulence in a slim-box without the front and back walls with aspect ratio, $L:D:H=1:1/6:1$, in the Rayleigh number $Ra=[1\times10^8, 1\times10^{10}]$ for Prandtl number $Pr=0.7$. The velocity profile is successfully quantified by a two-layer function of a stress length, $\ell_u^+\approx \ell_0^+(z^+)^{3/2}\left[1+\left({z^+}/{z_{sub}^+}\right)^4\right]^{1/4}$, as proposed by She et al. (She 2017), though neither a Prandtl-Blasius-Pohlhausen type nor the log-law is seen in the viscous boundary layer. In contrast, the temperature profile in the plume-ejecting region is logarithmic for all simulated cases, being attributed to the emission of thermal plumes. The coefficient of the temperature log-law, $A$ can be described by composition of the thermal stress length $\ell^*_{\theta}$ and the thicknesses of thermal boundary layer $z^*_{sub}$ and $z^*_{buf}$, i.e. $A\simeq z^*_{sub}/\left(\ell^*_{\theta 0}{z^*_{buf}}^{3/2}\right)$. The adverse pressure gradient responsible for turning the wind direction contributes to thermal plumes gathering at the ejecting region and thus the log-law of temperature profile. The Nusselt number scaling and local heat flux of the present simulations are consistent with previous results in confined cells. Therefore, the slim-box RBC is a preferable system for investigating in-box kinetic and thermal structures of turbulent convection with the large-scale circulation on a fixed plane., Comment: 16 pages, 37 figures

To elucidate the inhibitory effects of different herbicides on soil nitrification, eight widely used herbicides, i.e., acetochlor, atrazine, dicamba, isoproturon, paraquat, puma, tribenuron-methyl, and 2,4-dichlorophenoxyacetic acid butyl ester (2,4-Dbe), which represent different chemical taxonomy were selected. Our results indicated that herbicide 2,4-Dbe displayed the best inhibitory effect on nitrification, followed by puma and tribenuron-methyl, whereas the remaining five herbicides exhibited less effect when 10 mg of active ingredient (A.I.) of every herbicide per kg of soil was applied in vegetable-planting soil. The inhibition appeared when 5–100 mg of A.I. 2,4-Dbe was employed, which was enhanced with an increment in its dose in both vegetable-planting and fluvo-aquic soils. However, the inhibitory effect of 10 mg of A. I. 2,4-Dbe exhibited obvious differences in these two types of soils, where the duration of inhibition was shorter as it only continued about a week in fluvo-aquic and calcic cambisols soils with strong nitrification activity but poorer effect as compared to 10 mg of dicyandiamide (DCD). In contrast, the duration of inhibition exceeded 2 months in dryland red and shajiang black soils with a weak nitrification activity which was equivalent to DCD. In addition, comparing with five nitrification inhibitors, 10 mg of 2,4-Dbe had better inhibition than the substituted pyrimidine (AM) and sulfocarbamide (SU), but was equivalent to DCD, nitrapirin, and 3,4-dimethylpyrazole phosphate (DMPP) at their recommended application rates in dryland red soil. These obtained data clearly indicated that 2,4-Dbe could play a stronger role as a nitrification inhibitor in soils.

Background T cells play a key role in controlling viral infections; however, the underlying mechanisms regulating their functions during human viral infections remain incompletely understood. Here, we used CD4 T cells derived from individuals with chronic viral infections or healthy T cells treated with camptothecin (CPT) - a topoisomerase I (Top 1) inhibitor - as a model to investigate the role of DNA topology in reprogramming telomeric DNA damage responses (DDR) and remodeling T cell functions. Results We demonstrated that Top 1 protein expression and enzyme activity were significantly inhibited, while the Top 1 cleavage complex (TOP1cc) was trapped in genomic DNA, in T cells derived from individuals with chronic viral (HCV, HBV, or HIV) infections. Top 1 inhibition by CPT treatment of healthy CD4 T cells caused topological DNA damage, telomere attrition, and T cell apoptosis or dysfunction via inducing Top1cc accumulation, PARP1 cleavage, and failure in DNA repair, thus recapitulating T cell dysregulation in the setting of chronic viral infections. Moreover, T cells from virally infected subjects with inhibited Top 1 activity were more vulnerable to CPT-induced topological DNA damage and cell apoptosis, indicating an important role for Top 1 in securing DNA integrity and cell survival. Conclusion These findings provide novel insights into the molecular mechanisms for immunomodulation by chronic viral infections via disrupting DNA topology to induce telomeric DNA damage, T cell senescence, apoptosis and dysfunction. As such, restoring the impaired DNA topologic machinery may offer a new strategy for maintaining T cell function against human viral diseases.

Background Dictyostelid cellular slime molds (dictyostelids) are microscopic throughout their entire life cycle. The vegetative phase consists of single-celled amoeboid forms which live in the soil/leaf litter microhabitat of fields and forests along with animal dung, where they feed upon bacteria and other microbes, grow, and multiply until the available food supply is exhausted. When this happens, the amoeboid forms aggregate together in large numbers to form multi-celled pseudoplasmodia, which then give rise to fruiting bodies (sorocarps) that consist of supportive stalks and unwalled sori containing propagative spores. Results Dictyostelium purpureum var. pseudosessile, a new variant of dictyostelid, is described herein, based on morphological features and molecular data. This new variant was isolated from soil samples collected in two tropical areas of China. The complete spore-to-spore life cycle of this species, which required 50 h, including spore germination, myxamoebae, cell aggregation, pseudoplasmodium, and sorocarp formation, was documented. Descriptions and illustrations are provided for this species based on our collections. Data from ontogeny, morphology and phylogeny analyses (SSU) of D. purpureum var. pseudosessile confirm that it is a Group 4 species according to the newly proposed classification of dictyostelids. Conclusions Our results suggest that the violet sori, widens at the midpoint of sorophore and simple recurved sorophore bases represent the prominent features for the new variant D. purpureum var. pseudosessile. The latter is a Group 4 species now known from two tropical areas of China where dictyostelids remains understudied. Electronic supplementary material The online version of this article (10.1186/s12862-019-1407-2) contains supplementary material, which is available to authorized users.

Dictyostelid cellular slime molds (dictyostelids) are key components of soil microbes. The Qinghai-Tibet Plateau is characterized by unique and important forest types because of the considerable range in elevation which exists. During the period of 2012, 2013 and 2016, 12 species of dictyostelids were yielded from samples collected in this region, including two new species and three new records for China. Six other species were new records for this region. Ontogeny, morphology, ultrastructure and systematic molecular analyses (SSU & ITS) of D. minimum and D. multiforme confirm that they are Goup 4 new species. The ornamentation of the surface of dictyostelids’ spores is the first time to be observed until now. In the SSU phylogenetic tree generated in the present study, Synstelium, not assigned to order and family before, was assigned to the clade Acytosteliaceae in the Acytosteliales firstly. To our knowledge, the study reported herein is the first investigation of dictyostelid biodiversity carried out at elevations above 2000 m. Sorocarp size, sorus size, spore length, ratio of sorus and sorophore, and ratio of sorus and spore size were positively correlated with increasing elevation and no linear correlated with forest type, according to the results of linear regression analysis.

Degeneration of the noradrenergic neurons has been reported in the brain of patients suffering from neurodegenerative diseases. However, their pathological characteristics during the neurodegenerative course and underlying mechanisms remain to be elucidated. In the present study, we used the neurotoxin camptothecin (CPT) to induce the DNA damage response in neuroblastoma SH-SY5Y cells, normal fibroblast cells, and primarily cultured locus coeruleus (LC) and raphe neurons to examine cellular responses and repair capabilities after neurotoxin exposure. To our knowledge, the present study is the first to show that noradrenergic SH-SY5Y cells are more sensitive to CPT-induced DNA damage and deficient in DNA repair, as compared to fibroblast cells. Furthermore, similar to SH-SY5Y cells, primarily cultured LC neurons are more sensitive to CPT-induced DNA damage and show a deficiency in repairing this damage. Moreover, while N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) exposure also results in DNA damage in cultured LC neurons, neither CPT nor DSP4 induce DNA damage in neuronal cultures from the raphe nuclei. Taken together, noradrenergic SH-SY5Y cells and LC neurons are sensitive to CPT-induced DNA damage and exhibit a repair deficiency, providing a mechanistic explanation for the pathological characteristics of LC degeneration when facing endogenous and environmental DNA-damaging insults in vivo.

The construction and application of a new type of composite material are achieved more and more attention. However, expected Sb2Se3/attapulgite composites aim to use the low price, and high adsorption of attapulgite in assembling Sb2Se3 is quite difficult to be acquired by a facile and benign environmental hydrothermal method. In this manuscript, we developed a new way for preparation of an emerging composite by means of Sb2O3 as a media linking Sb2Se3 and attapulgite together, and finally won an emerging composite Sb2Se3/Sb2O3@attapulgite, which presented an excellent catalytic properties for catalytic hydrogenation of p-nitrophenol. It was noted that the Sb2Se3/Sb2O3@attapulgite composites exhibited a high conversion rate for the hydrogenation of p-nitrophenol that was up to 90.7% within 15 min, which was far more than the 61.5% of Sb2Se3 sample. The excellent catalytic performance was attributed to the highly dispersion Sb2Se3 microbelts and Sb2Se3@Sb2O3@attapulgite rods, which would improve the adsorption of the reactant species and facility electronic transfer process of the catalytic hydrogenation of p-nitrophenol.

Dopamine β-hydroxylase (DBH) and norepinephrine (NE) transporter (NET) are the noradrenergic phenotypes for their functional importance to noradrenergic neurons. It is known that in vivo N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) treatment induces degeneration of noradrenergic terminals by interacting with NET and depleting intracellular NE. However, DSP4’s precise mechanism of action remains unclear. In this study various biochemical approaches were employed to test the hypothesis that DSP4 down-regulates the expression of DBH and NET, and to determine molecular mechanisms that may be involved. The results showed that treatment of SH-SY5Y neuroblastoma cells with DSP4 significantly decreased mRNA and protein levels of DBH and NET. DSP4-induced reduction of DBH mRNA and proteins, as well as NET proteins showed a time- and concentration-dependent manner. Flow cytometric analysis demonstrated that DSP4-treated cells were arrested predominantly in the S-phase, which was reversible. The arrest was confirmed by several DNA damage response markers (phosphorylation of H2AX and p53), suggesting that DSP4 causes replication stress which triggers cell cycle arrest via the S-phase checkpoints. Moreover, the comet assay verified that DSP4 induced single-strand DNA breaks. In summary, the present study demonstrated that DSP4 down-regulates the noradrenergic phenotypes, which may be mediated by its actions on DNA replication, leading to replication stress and cell cycle arrest. These action mechanisms of DSP4 may account for its degenerative consequence after systematic administration for animal models.

Homologous recombination (HR) and nonhomologous end joining (NHEJ) are two distinct DNA double-stranded break (DSB) repair pathways. Here, we report that DNA-dependent protein kinase (DNA-PK), the core component of NHEJ, partnering with DNA-damage checkpoint kinases ataxia telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR), regulates HR repair of DSBs. The regulation was accomplished through modulation of the p53 and replication protein A (RPA) interaction. We show that upon DNA damage, p53 and RPA were freed from a p53-RPA complex by simultaneous phosphorylations of RPA at the N-terminus of RPA32 subunit by DNA-PK and of p53 at Ser37 and Ser46 in a Chk1/Chk2-independent manner by ATR and ATM, respectively. Neither the phosphorylation of RPA nor of p53 alone could dissociate p53 and RPA. Furthermore, disruption of the release significantly compromised HR repair of DSBs. Our results reveal a mechanism for the crosstalk between HR repair and NHEJ through the co-regulation of p53-RPA interaction by DNA-PK, ATM and ATR.

Ionomers are co-polymers with ionic groups. One of the interesting applications of ionomer membranes is as electrolytes in proton exchange membrane (PEM) fuel cells. The most commonly used membranes in PEM fuel cells are perfluorosulfonic acid (PFSA) membranes, e.g., Nafion® from DuPontTM. Besides its dependency on temperature and hydration due to phase inversion and cluster formation, Nafion® as a polymer, exhibits strong time and rate effects. In this work, the stress–strain behavior of Nafion® at different strain rates has been obtained in an environmental chamber for various temperatures and hydrations. After a certain strain was reached in each test, stress relaxation was performed for an hour to observe the relaxation behavior of Nafion®. We attempted to use a nonlinear, time-dependent constitutive model to predict the hygro-thermomechanical behavior of Nafion®. Because a substantial component of the response is unrecoverable, a viscoplastic model was employed. The proposed two-layer viscoplasticity model consisted of an elastoplastic network that was in parallel with an elastic-viscous network (Maxwell model) which separates the rate-dependent and rate-independent behavior of the material. After obtaining the necessary parameters for different hydrations, this model showed reasonably accurate success in predicting the stress–strain behavior at different strain rates, and matched the relaxation test results. Finite element simulations based on the proposed two-layer viscoplasticity model were in good agreement with test results and can be used to study the stress–strain state of the ionomer membranes in fuel cell configurations.

In response to DNA damage, mammalian cells activate various DNA repair pathways to remove DNA lesions and, meanwhile, halt cell cycle progressions to allow sufficient time for repair. The nucleotide excision repair (NER) and the ATR-dependent cell cycle checkpoint activation are two major cellular responses to DNA damage induced by UV irradiation. However, how these two processes are coordinated in the response is poorly understood. Here we showed that the essential NER factor XPA (xeroderma pigmentosum group A) underwent nuclear accumulation upon UV irradiation, and strikingly, such an event occurred in an ATR (Ataxia-Telangiectasia mutated and RAD3-related)-dependent manner. Either treatment of cells with ATR kinase inhibitors or transfection of cells with small interfering RNA targeting ATR compromised the UV-induced XPA nuclear translocation. Consistently, the ATR-deficient cells displayed no substantial XPA nuclear translocation while the translocation remained intact in ATM (Ataxia-Telangiectasia mutated)-deficient cells in response to UV irradiation. Moreover, we found that ATR is required for the UV-induced nuclear focus formation of XPA. Taken together, our results suggested that the ATR checkpoint pathway may modulate NER activity through the regulation of XPA redistribution in human cells upon UV irradiation.

Replication protein A (RPA) is a eukaryotic single-stranded DNA-binding protein consisting of three subunits of 70-kDa, 32-kDa, and 14-kDa (RPA70, RPA32, RPA14, respectively). It is a protein essential for most cellular DNA metabolic pathways. Checkpoint proteins Rad9, Rad1 and Hus1 form a clamp-like complex which plays a central role in the DNA damage-induced checkpoint response. In this report, we presented the evidence that Rad9-Rad1-Hus1 complex directly interacted with RPA in human cells, and this interaction was mediated by the binding of Rad9 protein to both RPA70 and RPA32 subunits. In addition, the cellular interaction of Rad9-Rad1-Hus1 with RPA or hyperphosphorylated RPA was stimulated by UV irradiation or camptothecin treatment in a dose dependent manner. Such treatments also resulted in the co-localization of the nuclear foci formed with the two complexes. Consistently, knockdown of the RPA expression in cells by the small interference RNA (siRNA) blocked the DNA damage-dependent chromatin association of Rad9-Rad1-Hus1, and also inhibited the Rad9-Rad1-Hus1 complex formation. Taken together, our results suggest that Rad9-Rad1-Hus1 and RPA complexes collaboratively function in DNA damage responses, and that the RPA may serve as a regulator for the activity of Rad9-Rad1-Hus1 complex in the cellular checkpoint network.