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Pneumonia, such as acute lung injury (ALI), has been a type of lethal disease that is generally caused by uncontrolled inflammatory response and excessive generation of reactive oxygen species (ROS). Herein, we report Fe-curcumin-based nanoparticles (Fe-Cur NPs) with nanozyme functionalities in guiding the intracellular ROS scavenging and meanwhile exhibiting anti-inflammation efficacy for curing ALI. The nanoparticles are noncytotoxic when directing these biological activities. Mechanism studies for the anti-inflammation aspects of Fe-Cur NPs were systematically carried out, in which the infected cells and tissues were alleviated through downregulating levels of several important inflammatory cytokines (such as TNF-α, IL-1β, and IL-6), decreasing the intracellular Ca2+ release, inhibiting NLRP3 inflammasomes, and suppressing NF-κB signaling pathways. In addition, we performed both the intratracheal and intravenous injection of Fe-Cur NPs in mice experiencing ALI and, importantly, found that the accumulation of such nanozymes was enhanced in lung tissue (better than free curcumin drugs), demonstrating its promising therapeutic efficiency in two different administration methods. We showed that the inflammation reduction of Fe-Cur NPs was effective in animal experiments and that ROS scavenging was also effectively achieved in lung tissue. Finally, we revealed that Fe-Cur NPs can decrease the level of macrophage cells (CD11bloF4/80hi) and CD3+CD45+ T cells in mice, which could help suppress the inflammation cytokine storm caused by ALI. Overall, this work has developed the strategy of using Fe-Cur NPs as nanozymes to scavenge intracellular ROS and as an anti-inflammation nanodrugs to synergistically cure ALI, which may serve as a promising therapeutic agent in the clinical treatment of this deadly disease. Fe-Cur NP nanozymes were designed to attenuate ALI by clearing intracellular ROS and alleviating inflammation synergistically. Relevant cytokines, inflammasomes, and signaling pathways were studied., Fe-Cur NP nanozymes were designed to attenuate ALI by clearing intracellular ROS and alleviating inflammation synergistically. Relevant cytokines, inflammasomes, and signaling pathways were studied.

Triple-negative breast cancer (TNBC) is an aggressive and highly lethal disease. The lack of targeted therapies and poor patient outcome have fostered efforts to discover new molecular targets to treat patients with TNBC. Here, we showed that baculoviral IAP repeat containing 6 (BIRC6) is overexpressed and positively correlated with epidermal growth factor (EGF) receptor (EGFR) in TNBC cells and tissues and that BIRC6 overexpression is associated with poor patient survival. Mechanistic studies revealed that BIRC6 stability is increased by EGF-JNK signaling, which prevents ubiquitination and degradation of BIRC6 mediated by the E3 ubiquitin ligase HECTD1. BIRC6 in turn decreases SMAC expression by inducing the ubiquitin-proteasome pathway, thereby antagonizing apoptosis and promoting the proliferation, colony formation, tumorsphere formation, and tumor growth capacity of TNBC cells. Therapeutically, the PEGylated cationic lipid nanoparticle (pCLN)-assisted delivery of BIRC6 small interfering RNA (siRNA) efficiently silences BIRC6 expression in TNBC cells, thus suppressing TNBC cell growth in vitro and in vivo, and its antitumor activity is significantly superior to that of the EGFR inhibitor gefitinib. Our findings identify an important regulatory mechanism of BIRC6 overexpression and provide a potential therapeutic option for treating TNBC., Graphical abstract, TNBC is the most aggressive subtype of breast cancer, and discovery of new targeted therapies is required. Our findings show that EGF-JNK-HECTD1 signaling can drive the overexpression of BIRC6 in TNBC. Targeting BIRC6 with lipid nanoparticle-coated siRNA represents a very promising approach for treating TNBC.

DYT-TOR1A or DYT1 early-onset generalized dystonia is an inherited movement disorder characterized by sustained muscle contractions causing twisting, repetitive movements, or abnormal postures. The majority of the DYT1 dystonia patients have a trinucleotide GAG deletion in DYT1/TOR1A. Trihexyphenidyl (THP), an antagonist for excitatory muscarinic acetylcholine receptor M1, is commonly used to treat dystonia. Dyt1 heterozygous ΔGAG knock-in (KI) mice, which have the corresponding mutation, exhibit impaired motor-skill transfer. Here, the effect of THP injection during the treadmill training period on the motor-skill transfer to the accelerated rotarod performance was examined. THP treatment reversed the motor-skill transfer impairment in Dyt1 KI mice. Immunohistochemistry showed that Dyt1 KI mice had a significant reduction of the dorsolateral striatal cholinergic interneurons. In contrast, Western blot analysis showed no significant alteration in the expression levels of the striatal enzymes and transporters involved in the acetylcholine metabolism. The results suggest a functional alteration of the cholinergic system underlying the impairment of motor-skill transfer and the pathogenesis of DYT1 dystonia. Training with THP in a motor task may improve another motor skill performance in DYT1 dystonia.

BACKGROUND AND PURPOSE This study was undertaken to screen the circular RNAs (circRNAs) influencing matrix metalloproteinase 9 (MMP9) through the competing endogenous RNA (ceRNA) network and evaluate the prognostic value of these circRNAs for acute ischemic stroke. METHODS A total of 220 ischemic stroke patients and 62 healthy subjects were included in this study. RNA was isolated from blood collected in PAXgene tubes. Illumina sequencing, quantitative real-time polymerase chain reaction (qRT-PCR) validation, and luciferase reporter assay were explored to construct and verify the existence of a circRNA-microRNA (miRNA)-matrix metalloproteinase-9 (MMP9) network. The 215 ischemic stroke patients were recruited in a prognostic cohort. They were prospectively followed up for 3 months after stroke onset, and a poor functional outcome was defined as a major disability or death. RESULTS After Illumina sequencing, six circRNAs were predicted to bind miRNAs and then regulate MMP9 messenger RNA (mRNA). qRT-PCR showed that only circSKA3 was significantly increased in ischemic stroke patients compared to healthy controls and positively associated with MMP9 mRNA expression. Luciferase reporter assay further verified a direct interaction between circSKA3, MMP9, and hsa-miR-6796-5p. Patients in the top tertile of circSKA3 had a 2.672-fold (p

Background: The activation of alveolar macrophages (AMs) modulated via leucine-rich repeat (NLR) pyrin domain containing 3 (NLRP3) inflammasome activation is key to the progression of renal ischemia/reperfusion (rI/R)-mediated acute lung injury (ALI). Sirtuin-1 (SIRT1) can attenuate NLRP3 inflammasome activation during I/R stress and may be an important mechanism underlying ALI pathogenesis. Penehyclidine hydrochloride (PHC), an anticholinergic drug, exerts protective effects against rI/R-mediated ALI. This study aimed to decipher the effects of PHC on SIRT1 activation and the underlying mechanism of the protective activity of PHC against rI/R-mediated ALI.Materials and methods: We used an ALI rat model and the rat AMs cell line NR8383 to assess the degree of lung injury in vivo and in vitro.Results: The results show that PHC attenuates rI/R-mediated lung injury indices, myeloperoxidase, and apoptosis in vivo. It decreases the rI/R-mediated release of prostaglandin E2 and nitric oxide, mitochondrial reactive oxygen species production, and the activity of NADPH oxidase-4 in vitro. PHC ameliorates the rI/R-induced activation of the thioredoxin-interacting protein, caspase 1 (P10 unit), and NLRP3 inflammasome, along with reduced activation of interleukin-1β and interleukin-18 in vitro. We show that PHC alleviates the rI/R-induced reduction of SIRT1 and the depletion of SIRT1 eliminates the ameliorating activity of PHC on the NLRP3 inflammasome activation in vitro. Conclusions: In summary, the findings suggest that PHC ameliorates the rI/R-mediated ALI through the SIRT1-mediated NLRP3 inflammasome activation.

Adrenocortical carcinoma (ACC) is a rare but aggressive disease that lacks definitive treatment. We aim to evaluate role of ASXL1 in ACC and exploit its therapeutic merits therein. We performed in silico reproduction of datasets of the Cancer Genome Atlas (TCGA), GDSC (Genomics of Drug Sensitivity in Cancer) and Human Protein Atlas using platforms of cBioPortal, UALCAN, NET-GE, GSEA and GEPIA. Validation in ACC was performed in tissue, in vitro and in vivo using the NCI-H295R and SW-13 cells. ASXL1 was gained in over 50% of ACC cases with its mRNA overexpressed in DNA gained cases. ASXL1 overexpression was associated with recurrence and worsened prognosis in ACC. ASXL1 gain was associated with resistance to etoposide, doxorubicin and cisplatin (EDP). ASXL1 expression was positively correlated with FSCN1 expression. Targeting ASXL1 significantly impaired fitness of ACC cells, which could be in part rescued by FSCN1 overexpression. Targeting FSCN1 however could not rescue resistance to EDP induced by ASXL1 overexpression. Targeting ASXL1 sensitized ACC cells to EDP regimen but constitutive ASXL3 overexpression in SW-13 cells could induce resistance upon prolonged treatment. Functional gain of ASXL1 was common in ACC and exerted pro-tumorigenic and chemoresistance role. Targeting ASXL1 hold promise to ACC treatment.

This paper proposes a multi-objective integrated optimization model of production scheduling and machine maintenance to find the optimal production sequence and preventive maintenance (PM) decisions. This model considers the setup time, the learning-forgetting effects and the multi-degradation effects. The setup time and the learning-forgetting effects are associated with jobs' similarities and PM decisions. The multi-degradation effects including machine deterioration, failure rate and quality characteristic loss determine the stochastic nature of the objectives. A hybrid maintenance strategy combining imperfect PM and minimal repair (MR) is adopted to effectively reduce the failure frequency and improve the processing quality. Then, the multi-objective solution is simplified by normalizing cost, time and utilization. The local search and the elitism strategy are conducted to avoid the solutions falling into local optimum and losing the best chromosome during evolutions. Finally, a case study of automobile engine manufacturing shows that our proposed model can reduce the total maintenance costs by 27%, shorten the total processing time by 3%, as well as improve the machine utilization by 3%.

Metal-semiconductor piezo-photocatalysts are generally investigated due to their high photocatalytic performances by the coupling effect of piezotronics and localized surface plasmon resonance (LSPR). However, the mechanism is still indistinct, even the charge migration route is disputable. Here, the electron migration from Ag to BaTiO3 has been confirmed by electron spin resonance (ESR) and radical trapping experiments. Furthermore, this work first proposes that piezoelectric field can promote the photocatalytic properties through electrical modulation of plasmon-exciton interaction. To exactly reveal the mechanism, the piezo-photocatalysis process is fully simulated by numerical analysis and finite element method (FEM). The unabridged mechanism of piezotronics boosted photocatalysis of LSPR-BaTiO3 shows that piezoelectric field can modulate LSPR to generate more hot electrons, suppress Schottky barrier for improved hot electron injection from Ag to BaTiO3 and restrain the recombination of electron–hole pairs by spatial separation of opposite charges.

Recent works suggest that using knowledge transfer strategies to tackle cross-domain diagnosis problems is promising for achieving engineering diagnosis. This article presents a diagnosis scheme for rolling bearing under a challenging domain generalization scenario, in which more potential discrepancies among multiple source domains are eliminated and only normal samples of the target domain are available during the training stage. To achieve sufficient generalization performance, a diagnosis scheme combining some a priori diagnosis knowledge and a deep domain generalization network for fault diagnosis (DDGFD) is elaborated. Through signal preprocessing steps guided by the a priori diagnosis knowledge, the inputs of DDGFD with a primary consistent meaning across domains are constructed from the vibration signal. On this basis, DDGFD would intently release its talent on learning discriminative and domain-invariant fault features from source domains, and then generalize the learned knowledge to identify unseen target samples. On cross-domain tasks organized using broad bearing data sets, the superiority of DDGFD is validated by comparing its performance with various data-driven diagnosis methods.

Restless legs syndrome (RLS) is a chronic sensorimotor disorder diagnosed by clinical symptoms. It is challenging to translate the diagnostic self-reported features of RLS to animals. To help researchers design their experiments, a task force was convened to develop consensus guidelines for experimental readouts in RLS animal models. The RLS clinical diagnostic criteria were used as a starting point. After soliciting additional important clinical features of RLS, a consensus set of methods and outcome measures intent on capturing these features-in the absence of a face-to-face interview-was generated and subsequently prioritized by the task force. These were, in turn, translated into corresponding methods and outcome measures for research on laboratory rats and mice and used to generate the final recommendations. The task force recommended activity monitoring and polysomnography as principal tools in assessing RLS-like behavior in rodents. Data derived from these methods were determined to be the preferred surrogate measures for the urge to move, the principal defining feature of RLS. The same tools may be used to objectively demonstrate sleep-state features highly associated with RLS, such as sleep disturbance and number and periodicity of limb movements. Pharmacological challenges and dietary or other manipulations that affect iron availability are desirable to aggravate or improve RLS-like behavior and lend greater confidence that the animal model being proffered replicates key clinical features of RLS. These guidelines provide the first consensus experimental framework for researchers to use when developing new rodent models of RLS. © 2020 International Parkinson and Movement Disorder Society.

Cooperative offloading in mobile edge computing enables resource-constrained edge clouds to help each other with computation-intensive tasks. However, the power of such offloading could not be fully unleashed, unless trust risks in collaboration are properly managed. As tasks are outsourced and processed at the network edge, completion latency usually presents high variability that can harm the offered service levels. By jointly considering these two challenges, we propose OLCD, an Online Learning-aided Cooperative offloaDing mechanism under the scenario where computation offloading is organized based on accumulated social trust. Under co-provisioning of computation, transmission, and trust services, trust propagation is performed along the multi-hop offloading path such that tasks are allowed to be fulfilled by powerful edge clouds. We harness Lyapunov optimization to exploit the spatial-temporal optimality of long-term system cost minimization problem. By gap-preserving transformation, we decouple the series of bidirectional offloading problems so that it suffices to solve a separate decision problem for each edge cloud. The optimal offloading control can not materialize without complete latency knowledge. To adapt to latency variability, we resort to the delayed online learning technique to facilitate completion latency prediction under long-duration processing, which is fed as input to queued-based offloading control policy. Such predictive control is specially designed to minimize the loss due to prediction errors over time. We theoretically prove that OLCD guarantees close-to-optimal system performance even with inaccurate prediction, but its robustness is achieved at the expense of decreased stability. Trace-driven simulations demonstrate the efficiency of OLCD as well as its superiorities over prior related work.

Background We aim to explore association between copy number alteration (CNA) and sensitivity to common tyrosine kinase inhibitors (TKIs) used in clear-cell renal cell carcinoma (ccRCC) treatment. Methods CNA with related sensitivity profiles were extracted from the Genomics of Drug Sensitivity in Cancer (GDSC) dataset and was cross-referenced with common CNA in ccRCC in the Cancer Genome Atlas (TCGA) dataset. Functional annotation was profiled using GSEA and NET-GE. Target genes within cytobands of interest were screened in silico and validated in vitro using proliferation assays in A498 and 786-O ccRCC cells. Results Four TKIs (Sunitinib, Cabozantinib, Axitinib and Sorafenib) that were clinically used in ccRCC were selected. In silico analysis showed gain of 20q (+20q) occurred in ~ 23% of cases and was associated with resistance to all four TKIs; loss of 14q (−14q) occurred in ~ 39% of cases and was associated with resistance to Sunitinib and Sorafenib; loss of 18p (−18p) occurred in ~ 39% of cases and was associated with sensitivity to Sunitinib and Sorafenib. All 3 CNAs were associated with worsened prognosis, respectively. Candidate target genes included of RBL1 on 20q, KLHL33 on 14q and ARHGAP28 on18q. In vitro validation showed RBL1 overexpression induced resistance to Sunitinib and Cabozantinib; KLHL33 silencing induced resistance to Sunitinib; ARHGAP28 silencing induced sensitivity to Cabozantinib. Functional annotation indicated FoxO signaling, hypoxic response and Wnt pathway, and Rho-related cellular adhesion were mechanistically associated with +20q, −14q and −18p, respectively. Conclusion Common CNAs in ccRCC are associated with cancer-intrinsic cross-sensitivity to common TKIs. Further validation and functional analyses are therefore needed.

Shared bicycle is an emerging form of public transportation in China and around the world. However, the bacterial community and drug-resistant microbiome on these bicycles have not been reported. Samples from 10 shared bicycles were observed by scanning electron microscopy (SEM). Nine samples collected from 90 shared bicycles in three different kinds of location (hospital, metro station, shopping mall) were used for full-length 16S rDNA gene analysis to figure out the bacterial composition of the shared bicycle. Samples from 32 shared bicycles were used to investigate culturable drug-resistant bacteria of the shared bicycle bacterial community. It was found that in the shared bicycle bacterial community, Bacillus was the most abundant bacteria, as determined by both SEM observation and full-length 16S rDNA gene analysis. For the analysis of drug-resistant bacteria, Bacillus showed the strongest drug resist ability. Moreover, the resistances to bacitracin and sulfamethoxazole were the most common among all types of bacteria. Our study provides an important reference for the prevention of the potential spread of drug-resistant bacteria through shared bicycles.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel β-coronavirus, is the main pathogenic agent of the rapidly spreading pneumonia called coronavirus disease 2019 (COVID-19). SARS-CoV-2 infects much more people, especially the elder population, around the world than other coronavirus, such as SARS-CoV and MERS-CoV, which is challenging current global public health system. Beyond the pathogenesis of SARS-CoV-2, microbial coinfection plays an important role in the occurrence and development of SARS-CoV-2 infection by raising the difficulties of diagnosis, treatment, prognosis of COVID-19, and even increasing the disease symptom and mortality. We summarize the coinfection of virus, bacteria and fungi with SARS-CoV-2, their effects on COVID-19, the reasons of coinfection, and the diagnosis to emphasize the importance of microbial coinfection in COVID-19. Key points • Microbial coinfection is a nonnegligible factor in COVID-19. • Microbial coinfection exacerbates the processes of the occurrence, development and prognosis of COVID-19, and the difficulties of clinical diagnosis and treatment. • Different virus, bacteria, and fungi contributed to the coinfection with SARS-CoV-2.

Background Chromosomal rearrangements are common in clear cell renal cell carcinoma (ccRCC) and their roles in mediating sensitivity to tyrosine kinase inhibitors (TKIs) and mTOR inhibitors (mTORi) remain elusive. Methods We developed an in silico strategy by screening copy number variance (CNV) that was potentially related to TKI or mTORi sensitivity in ccRCC by reproducing the TCGA and GDSC datasets. Candidate genes should be both significantly prognostic and related to drug sensitivity or resistance, and were then validated in vitro. Results ADCYAP1 loss and GNAS gain were associated with sensitivity and resistance and to Cabozantinib, respectively. ACRBP gain and CTBP1 loss were associated with sensitivity and resistance and to Pazopanib, respectively. CDKN2A loss and SULT1A3 gain were associated with sensitivity and resistance and to Temsirolimus, respectively. CCNE1 gain was associated with resistance to Axitinib and LRP10 loss was associated with resistance to Sunitinib. Mutivariate analysis showed ADCYAP1, GNAS, and CCNE1 remained independently prognostic when adjusted for the rest. Conclusion Here we show CNVs of several genes that are associated with sensitivity and resistance to commonly used TKIs and mTORi in ccRCC. Further validation and functional analyses are therefore needed., Sensitivity and resistance to cabozantinib.

Recent genome-wide association studies (GWAS) have found cerebellum as a top hit for sleep regulation. Restless legs syndrome (RLS) is a sleep-related sensorimotor disorder characterized by uncomfortable sensations in the extremities, generally at night, which are often relieved by movements. Clinical studies have found that RLS patients have structural and functional abnormalities in the cerebellum. However, whether and how cerebellar pathology contributes to sleep regulation and RLS is not known. GWAS identified polymorphisms in BTBD9 conferring a higher risk of sleep disruption and RLS. Knockout of the BTBD9 homolog in mice (Btbd9) and fly results in motor restlessness and sleep disruption. We performed manganese-enhanced magnetic resonance imaging on the Btbd9 knockout mice and found decreased neural activities in the cerebellum, especially in lobules VIII, X, and the deep cerebellar nuclei. Electrophysiological recording of Purkinje cells (PCs) from Btbd9 knockout mice revealed an increased number of non-tonic PCs. Tonic PCs showed increased spontaneous activity and intrinsic excitability. To further investigate the cerebellar contribution to RLS and sleep-like behaviors, we generated PC-specific Btbd9 knockout mice (Btbd9 pKO) and performed behavioral studies. Btbd9 pKO mice showed significant motor restlessness during the rest phase but not in the active phase. Btbd9 pKO mice also had an increased probability of waking at rest. Unlike the Btbd9 knockout mice, there was no increased thermal sensation in the Btbd9 pKO. Our results indicate that the Btbd9 knockout influences the PC activity; dysfunction in the cerebellum may contribute to the motor restlessness found in the Btbd9 knockout mice.

The global rise in fatty liver is a major public health problem. Thus, it is critical to identify both global and population‐specific genetic variants associated with liver fat. We conducted a genome‐wide association study (GWAS) of percent liver fat and nonalcoholic fatty liver disease (NAFLD) assessed by magnetic resonance imaging in 1,709 participants from the population‐based Multiethnic Cohort Adiposity Phenotype Study. Our participants comprised older adults of five U.S. racial/ethnic groups: African Americans (n = 277), Japanese Americans (n = 424), Latinos (n = 348), Native Hawaiians (n = 274), and European Americans (n = 386). The established missense risk variant rs738409 located in patatin‐like phospholipase domain containing 3 (PNPLA3) at 22q13 was confirmed to be associated with percent liver fat (P = 3.52 × 10−15) but more strongly in women than men (P heterogeneity = 0.002). Its frequency correlated with the prevalence of NAFLD across the five ethnic/racial groups. Rs738409 was also associated with homeostasis model assessment of insulin resistance (HOMA‐IR) (beta = 0.028; P = 0.009) and circulating levels of insulin (beta = 0.022; P = 0.020) and alanine aminotransferase (beta = 0.016; P = 0.030). A novel association of percent liver fat with rs77249491 (located at 6q13 between limb region 1 domain containing 1 [LMBRD1] and collagen type XIX alpha 1 chain [COL19A1] (P = 1.42 × 10−8) was also observed. Rs7724941 was associated with HOMA‐IR (beta = 0.12; P = 0.0005), insulin (beta = 0.11; P = 0.0003), triglycerides (beta = 0.059; P = 0.01), high‐density lipoprotein (beta = −0.046; P = 0.04), and sex hormone binding globulin (beta = −0.084; P = 0.0012). This variant was present in Japanese Americans (minor allele frequency [MAF], 8%) and Native Hawaiians (MAF, 2%). Conclusion: We replicated the PNPLA3 rs738409 association in a multiethnic population and identified a novel liver fat risk variant in Japanese Americans and Native Hawaiians. GWASes of percent liver fat in East Asian and Oceanic populations are needed to replicate the rs77249491 association., We conducted a genome‐wide association study of % liver fat and NAFLD assessed by magnetic resonance imaging (MRI) in 1,709 participants from the population‐based Multiethnic Cohort‐Adiposity Phenotype Study (MEC‐APS), comprised of older adults of five US racial/ethnic groups: African Americans (n = 277), Japanese Americans (n = 424), Latinos (n = 348), Native Hawaiians (n = 274), and European Americans (n = 386). The established missense risk variant, rs738409, located in PNPLA3 at 22q13, was confirmed to be associated with % liver fat (P = 3.52 × 10−15). Also, a novel association of % liver fat with rs77249491 (located at 6q13 between LMBRD1 and COL19A1; P = 1.42 × 108) was observed.

SARS-CoV-2, a novel emerging coronavirus, has caused severe disease (COVID-19), and rapidly spread worldwide since the beginning of 2020. SARS-CoV-2 mainly spreads by coughing, sneezing, droplet inhalation, and contact. SARS-CoV-2 has been detected in saliva samples, making saliva a potential transmission route for COVID-19. The participants in dental practice confront a particular risk of SARS-CoV-2 infection due to close contact with the patients and potential exposure to saliva-contaminated droplets and aerosols generated during dental procedures. In addition, saliva-contaminated surfaces could lead to potential cross-infection. Hence, the control of saliva-related transmission in the dental clinic is critical, particularly in the epidemic period of COVID-19. Based on our experience of the COVID-19 epidemic, some protective measures that can help reduce the risk of saliva-related transmission are suggested, in order to avoid the potential spread of SARS-CoV-2 among patients, visitors, and dental practitioners.

Restless legs syndrome (RLS) is characterized by an irresistible need to move the legs while sitting or lying at night with insomnia as a frequent consequence. Human RLS has been associated with abnormalities in the endogenous opioid system, the dopaminergic system, the iron regulatory system, anemia, and inflammatory and auto-immune disorders. Our previous work indicates that mice lacking all three subtypes of opioid receptors have a phenotype similar to that of human RLS. To study the roles of each opioid receptor subtype in RLS, we first used mu opioid receptor knockout (MOR KO) mice based on our earlier studies using postmortem brain and cell culture. The KO mice showed decreased hemoglobin, hematocrit, and red blood cells (RBCs), with an appearance of microcytic RBCs indicating anemia. Together with decreased serum iron and transferrin, but increased ferritin levels, the anemia is similar to that seen with chronic inflammation in humans. A decreased serum iron level was also observed in the wildtype mice treated with an MOR antagonist. Iron was increased in the liver and spleen of the KO mice. Normal circadian variations in the dopaminergic and serotoninergic systems were absent in the KO mice. The KO mice showed hyperactivity and increased thermal sensitivity in wakefulness primarily during what would normally be the sleep phase similar to that seen in human RLS. Deficits in endogenous opioid system transmission could predispose to anemia of inflammation and loss of circadian variations in dopaminergic or serotonergic systems, thereby contributing to an RLS-like phenotype.

The data-driven diagnosis methods based on conventional machine-learning techniques have been widely developed in recent years. However, the assumption of conventional methods that the training and test data should be identically distributed is usually unsatisfied in actual diagnosis scenario. While there are several existing works that have been studied to construct diagnosis models by transfer learning methods, most of them are only focused on learning from a single source. Actually, how to discover effective and general diagnosis knowledge from multiple related source domains and further generalize the learned knowledge to new target tasks is crucial to data-driven fault diagnosis. To this end, this paper proposes a novel intelligent fault identification method based on multiple source domains. First, the method describes the discriminant structure of each source domain as a point of Grassmann manifold using local Fisher discriminant analysis. Through preserving the within-class local structure, local Fisher discriminant analysis can learn effective discriminant directions from multimodal fault data. Second, the mean subspace of source domains is computed on the Grassmann manifold through Karcher mean. The mean subspace can be viewed as a representation of the general diagnosis structure that can facilitate the construction of the diagnosis model for the target domain. Experiments on bearing fault diagnosis tasks verify the effectiveness of the proposed method.

In recent years, Convolutional neural networks (CNNs) have achieved start-of-art performance in the fault diagnosis field. If there is no available information on the unseen operating conditions, the model trained on the seen operating condition cannot perform well. One of the feasible strategies is to enhance the generalization ability of the network on various seen operating conditions. We introduce the center loss to the traditional CNN and build an end-to-end fault diagnosis framework (called CNN-C). By minimizing the intra-class variations, center loss cluster the learned features across various seen operating conditions. With the joint supervision of the center loss and the softmax loss, the learned features of the same class could minimize the domain difference across various seen operating conditions while the features of different classes are separable. The generalization ability of network is improved on unseen operating conditions. Compared with the shallow methods and traditional CNN, the proposed method is promising to deal with the fault diagnosis tasks of the bearing and gearbox.

External-cavity diode laser (ECDL) has important applications in many fundamental and applied researches. Here we report a method to fast and widely tune the frequency of a stabilized ECDL. The beat frequency between the ECDL and a frequency-locked reference laser is identified by the voltage-controlled oscillator contained in a phase detector, whose output voltage is subtracted from the flexibly controlled PC signal to generate an error signal for stabilizing the ECDL. The output frequency of the stabilized ECDL can be shifted at a short characteristic time of ∼ 150 μs within a range of ∼ 620 MHz. The wide and fast-frequency tuning achieved by our method is compared with other previous works. We demonstrated the performance of our method by the efficient sub-Doppler cooling of Cs atoms with the temperature as low as 6 μK.

A comprehensive risk assessment of different types of natural disasters at the county level can promote quantitative disaster risk assessment and can provide a scientific basis for the formulation of disaster prevention measures. Focusing on climate-related hazards and based on natural disaster risk assessment theories and methods, this study integrates disaster statistics, meteorological data, geographic information, and other multivariate data to quantify the hazards of various disasters and the vulnerability and exposure of hazard-bearing bodies and conducts an integrated assessment of comprehensive risks of multiple climate-related hazards in Cangnan County, Zhejiang Province. Typhoon disaster risk is high in the central and northern parts of this county and low in its surroundings, with high-risk areas mainly distributed in Lingxi Town to the north. The comprehensive risk distribution patterns of drought and flood disasters in Cangnan County are similar: low in the south and high in the north. With the method of standard deviation, the comprehensive risk of multiple climate-related hazards in Cangnan County shows a distribution pattern of being low in the south and high in the north, with high risk in the northeast and low risk in the northwest and south.

Background: Accumulation of uric acid during muscular trauma is potentially a causative factor of damage-associated molecular patterns (DAMPs) involved in the development of muscle hyperalgesia. Neutrophil extracellular traps (NETs), DNA-based reticular structures to capture DAMPs, play a central role in the onset of pain in gout attacks associated with hyperuricemia; however, their association with muscle hyperalgesia due to overuse injuries remains unknown. Therefore, the aim of this study was to investigate the involvement of NETs via the elevation of local uric acid level in muscle nociception.Methods: The triceps surae muscles (TSMs) in the unilateral hindlimb of mice were repeatedly stimulated with electrical pulses to induce excessive muscle contraction, and the contralateral TSM was used as a control. In addition to mechanical nociceptive thresholds, tissue uric acid levels, neutrophil recruitment, protein amount, and histological distribution of citrullinated histone 3 (citH3), a major marker of NETs, were investigated. Furthermore, whether neutrophil depletion, extracellular DNA cleavage (deoxyribonuclease I), and administration of the urate-lowering agent febuxostat, a xanthine oxidase inhibitor, improved muscle hyperalgesia due to NET accumulation was examined. Using a combination of multiphoton imaging analysis and intravital fluorescence staining, we also evaluated the intramuscular distribution of NET accumulation in stimulated TSMs.Results: CitH3 expression upon neutrophil recruitment significantly increased in the stimulated TSMs tissues with an increase in tissue uric acid levels. However, neutrophil depletion and extracellular DNA cleavage prevented the increase in uric acid levels in damaged muscle tissues. Furthermore, febuxostat administration significantly improved muscle hyperalgesia, with decreases not only in citH3 and tissue uric acid levels, but also in neutrophil recruitment. Interestingly, the intramuscular distribution of NETs in the stimulated TSM was predominantly observed in the myofascial region.Conclusions: Our findings suggest that NET accumulation caused by excessive muscle contraction was strongly associated with the pathogenesis of muscle hyperalgesia. Further, the mechanism underlying induction of locally recruited neutrophils forming NETs was increased tissue uric acid levels, which potentially plays a significant role in creating a vicious circle of muscle pain.

Crowdsourcing is an effective paradigm in human centric computing for addressing problems by utilizing human computation power, especially in booming social Internet of Things (IoT). By leveraging mutual friendship between computing entities (i.e., workers), collaborative tasks can thus be routed and finally fulfilled by multihop friends with high expertise. However, crowdsourcing in social IoT may reveal the privacy of task requesters which results in a large dilemma. In this paper, we focus on designing a multihop routing incentive mechanism which can also preserve task requester’s privacy. Specifically, a utility maximization problem under privacy and budget feasibility constraints is formulated. Defining the conditions for privacy insurance, we give guidelines on how many subtasks should an entire task be divided into, and analyze the tradeoff between privacy and task accuracy. To enable efficient crowdsourcing task routing in social IoT, we first consider 1-hop myopic routing case and propose a near-optimal task assignment algorithm with 1/2 approximation ratio for an arbitrary prior knowledge. We further design multihop payment policy to establish an equilibrium where workers are motivated to forward subtasks to their friends with the best expertise. The extensive simulations validate that our mechanism achieves a high level of average information gain with modest privacy guarantee.

Bladder cancer is one of the most commonly diagnosed cancers worldwide and causes the highest lifetime treatment costs per patient. Bladder cancer is most likely to metastasize through lymphatic ducts, and once the lymph nodes are involved, the prognosis is poorly and finitely improved by current modalities. The underlying metastatic mechanism for bladder cancer is thus becoming a research focus to date. To identify relevant published data, an online search of the PubMed/Medline archives was performed to locate original articles and review articles regarding lymphangiogenesis and lymphatic metastasis in urinary bladder cancer (UBC), and was limited to articles in English published between 1998 and 2018. A further search of the clinical trials.gov search engine was conducted to identify both trials with results available and those with results not yet available. Herein, we summarized the unique mechanisms and biomarkers involved in the malignant progression of bladder cancer as well as their emerging roles in therapeutics, and that current data suggests that lymphangiogenesis and lymph node invasion are important prognostic factors for UBC. The growing knowledge about their roles in bladder cancers provides the basis for novel therapeutic strategies. In addition, more basic and clinical research needs to be conducted in order to identify further accurate predictive molecules and relevant mechanisms.

In general, the 3 D printed medical models are made based on virtual digital models obtained from machines such as the computed tomography scanner. However, due to the limited accuracy of CT scanning technology, which is usually 1 millimeter, there are differences between scanned results and the real structure. Besides, the collected data can hardly be printed directly because of some errors in the model. In this paper, we present a general and efficient procedure to process the digital skull data to make the printed structures meet the requirements of anatomy education, which combines the use of five 3 D manipulation tools and the procedure can be finished within 6 hours. Then the model is printed and compared with the cadaveric skull from frontal, left, right and anterior views respectively. The printed model can describe the correct structure and details of the skull clearly, which can be considered as a good alternative to the cadaveric skull. The manipulation procedure presented in this study is an easily available and cost-effective way to obtain a printed skull model from the original CT data, which has a considerable economic and social benefit for the medical education. The steps of the data processing can be performed easily. The cost for the 3 D printed model is also low. Outcomes of this study can be applied widely in processing skull data.

In terms of fast response problem of unanticipated marine target, it is necessary to design the satellite-ground-combined operation mechanism and planning algorithm for autonomous task planning. Firstly, based on the autonomous operation and task planning of remote sensing satellite group, it is divided into two parts: ground planning and satellite autonomous planning. Secondly, the satellite-ground-combined operation mechanism and operation flow for task planning are proposed after fully considering the resource characteristics and task demand characteristics of the ground and satellite. The satellite autonomous task planning algorithm based on extended contract net is designed. Through the simulation operation of the self-developed distributed simulation demonstration software, it shows that the operation mechanism can coordinate and cooperate effectively between the satellite autonomous task planning and ground planning. It can give full play to the advantages of the ground computing resources, reflect the control intention, make full use of the real-time feature and flexibility of the satellite calculation, and respond fast to the unanticipated task. Besides, it has solved problems of the untimely response of ground control on unanticipated observation task, the limitation of satellite computing resources and satellite-ground planning and coordination, which can effectively improve the responsiveness of remote sensing satellite to the observation task of maritime unanticipated target. Keywords: Fast response, Marine target surveillance, Mission planning, Multi-satellite system, Onboard autonomy

Data-driven fault diagnosis has been a hot topic in recent years with the development of machine learning techniques. However, the prerequisite that the training data and the test data should follow an identical distribution prevents the conventional data-driven diagnosis methods from being applied to the engineering diagnosis problems. To tackle this dilemma, cross-domain fault diagnosis using knowledge transfer strategy is becoming popular in the past five years. The diagnosis methods based on transfer learning aim to build models that can perform well on target tasks by leveraging knowledge from semantic related but distribution different source domains. This paper for the first time summarizes the state-of-art cross-domain fault diagnosis research works. The literatures are introduced from three different viewpoints: research motivations, cross-domain strategies, and application objects. In addition, the corresponding open-source fault datasets and several future directions are also presented. The survey provides readers a framework for better understanding and identifying the research status, challenges and future directions of cross-domain fault diagnosis.

Exposure to bisphenol A (BPA), triclosan and parabens is widespread but their impact on breast cancer risk remains unclear. This nested case-control study investigated endocrine-disrupting chemicals (EDCs) and breast cancer risk within the Multiethnic Cohort (MEC). We measured prediagnostic urinary BPA, triclosan and parabens in 1032 postmenopausal women with breast cancer (48 African American, 77 Latino, 155 Native Hawaiian, 478 Japanese American and 274 White) and 1030 individually matched controls, using a sensitive and validated liquid chromatography mass spectrometry assay. Conditional logistic regression was used to examine risk with these EDCs with adjustment for creatinine and potential confounders. In all women, breast cancer risk was not associated with BPA (Ptrend = 0.53) and was inversely associated with triclosan (ORT3 vs T1 = 0.83, 95% CI: 0.66-1.04, Ptrend = 0.045) and total parabens (ORT3 vs T1 = 0.77, 95% CI: 0.62-0.97, Ptrend = 0.03). While risk of hormone receptor positive (HR+) cancer was 20% to 23% lower among women in the upper two tertiles of paraben exposure (Ptrend = 0.02), risk of HR negative (HR-) was reduced 27% but only among those in the upper tertile of exposure. Although risk associations did not differ significantly by ethnicity or by body mass index (BMI), the inverse association with triclosan was observed mainly among overweight/obese women (ORT3 vs T1 = 0.76, 95% CI: 0.56-1.02, Ptrend = 0.02). In summary, breast cancer risk in a multiethnic population was unrelated to BPA and was weakly inversely associated with triclosan and paraben exposures. Studies with multiple urine samples collected before breast cancer diagnosis are needed to further investigate these EDCs and breast cancer risk.

Determining the altitude of side-scan sonar (SSS) above the seabed is critical to correct the geometric distortions in the sonar images. Usually, a technology named bottom tracking is applied to estimate the distance between the sonar and the seafloor. However, the traditional methods for bottom tracking often require pre-defined thresholds and complex optimization processes, which make it difficult to achieve ideal results in complex underwater environments without manual intervention. In this paper, a universal automatic bottom tracking method is proposed based on semantic segmentation. First, the waterfall images generated from SSS backscatter sequences are labeled as water column (WC) and seabed parts, then split into specific patches to build the training dataset. Second, a symmetrical information synthesis module (SISM) is designed and added to DeepLabv3+, which not only weakens the strong echoes in the WC area, but also gives the network the capability of considering the symmetry characteristic of bottom lines, and most importantly, the independent module can be easily combined with any other neural networks. Then, the integrated network is trained with the established dataset. Third, a coarse-to-fine segmentation strategy with the well-trained model is proposed to segment the SSS waterfall images quickly and accurately. Besides, a fast bottom line search algorithm is proposed to further reduce the time consumption of bottom tracking. Finally, the proposed method is validated by the data measured with several commonly used SSSs in various underwater environments. The results show that the proposed method can achieve the bottom tracking accuracy of 1.1 pixels of mean error and 1.26 pixels of standard deviation at the speed of 2128 ping/s, and is robust to interference factors.

Aiming at the task planning and scheduling problem of space object detection LEO constellation (SODLC) for detecting space objects in deep space background, a method of SODLC task satellite selection based on observation window projection analysis is proposed. This method projects the spatial relative relationships of the SODLC observation blind zone, observation range, and the initial spatial position of the objects onto the surface of the earth for detectable analysis of satellites and targets and binds the dynamic observation conditions to the satellite trajectory after projection calculation of the visible relationship between target changes. On this basis, combined with the features of SODLC with high orbital symmetry, the task satellite selection is divided into two steps: orbit plane selection and task satellite selection. The orbit planes are selected based on the longitude range of the ascending node with the geographic location of the targets, and the task satellites are selected according to the relative motion relationship between the satellites and the targets together with the constraints of observable conditions. The selection method simplifies the calculation process of scheduling and selecting task satellites. Simulation analysis prove the method has better task satellite selection efficiency. The method has high practical value for task planning and scheduling for event-driven SODLC.

Background. Metastasis is one of the most prevalent causes of death in cancer patients and the lungs are among the organs most commonly affected by metastasis. However, analysis of the incidence and prognosis of lung metastasis (LM) based on primary cancer sites is lacking. Methods. We enrolled cancer patients with LM from the Surveillance, Epidemiology, and End Results (SEER) database. The risk factors for LM were determined using multivariate logistics regression. Forest plots were used to compare the impact of with LM versus without LM alone among different primary caner site subgroups. Results. Among 1,525,441 cases, 47,537 presented with LM at initial diagnosis. Multivariate logistics regression revealed that male sex, older age, later T/N stage, unmarried status, and lack of insurance were risk factors for LM. The incidence of LM was 11.91% in bone cancer and 11.19% in pancreatic cancer. In terms of the distribution of primary cancers, 19.22% of LMs originated from the colon and rectum, with 11.63% from the kidneys. The median survival for LM cases was 6 months, with the best survival in testicular cancer (19 months) and bone cancer (12 months). Patients with LM had higher hazard ratio (HR) for mortality compared to those without LM, except for those with primary cancer in the brain ( P = 0.09 ). We stratified patients by primary cancer site, and subgroup analyses showed that LM had a significant negative impact on survival. The most significant was in thyroid cancer (HR = 44.79), followed by melanoma (HR = 24.26), prostate (HR = 16.0), breast (HR = 13.46), endometrial (HR = 12.64), testicular (HR = 12.31), and kidney (HR = 11.33) cancer (all P < 0.001 ). Conclusion. Patients presenting with LM had higher HR for mortality compared to those without LM, except for those with brain tumor. Clinicians should pay more attention to the occurrence of LM, especially in patients with a significantly increased HR for mortality, such as those with thyroid cancer, melanoma, and prostate cancer.

Bladder cancer is one of the most common malignancy in the urinary tract with high recurrence and drug resistance in clinics. Alternative treatments from existing drugs might be a promising strategy. Nitazoxanide (NTZ), an FDA-approved antiprotozoal drug, has got increasingly noticed because of its favorable safety profile and antitumor potential, yet the effects in bladder cancer and underlying mechanisms remain poorly understood. Herein, we find that NTZ induces mitochondrial damage and mitophagy initiation through PINK1-generated phospho-ubiquitin(pS65-Ub) and autophagy receptor-mediated pathway even in the absence of Atg5/Beclin1. Meanwhile, NTZ inhibits lysosomal degradation activity, leading to mitophagy flux impairment at late stage. Mitochondrial reactive oxygen species (ROS) production is critical in this process, as eliminating ROS with N-acetylcysteine (NAC) efficiently inhibits PINK1 signaling-mediated mitophagy initiation and alleviates lysosomal dysfunction. Co-treatment with NTZ and autophagy inhibitor Chloroquine (CQ) to aggravate mitophagy flux impairment promotes NTZ-induced apoptosis, while alleviation of mitophagy flux impairment with ROS scavenger reduces cell death. Moreover, we also discover a similar signaling response in the 3D bladder tumor spheroid after NTZ exposure. In vivo study reveals a significant inhibition of orthotopic bladder tumors with no obvious systemic toxicity. Together, our results uncover the anti-tumor activities of NTZ with the involvement of ROS-mediated mitophagy modulation at different stages and demonstrate it as a potential drug candidate for fighting against bladder tumors.

Background: A relatively high proportion of Asian American, Native Hawaiian, and Pacific Islander (AANHPI) females with lung cancer have never smoked. We used an integrative data approach to assemble a large-scale cohort to study lung cancer risk among AANHPIs by smoking status with attention to representation of specific AANHPI ethnic groups. Methods: We leveraged electronic health records (EHRs) from two healthcare systems—Sutter Health in northern California and Kaiser Permanente Hawai'i—that have high representation of AANHPI populations. We linked EHR data on lung cancer risk factors (i.e., smoking, lung diseases, infections, reproductive factors, and body size) to data on incident lung cancer diagnoses from statewide population-based cancer registries of California and Hawai'i for the period between 2000 and 2013. Geocoded address data were linked to data on neighborhood contextual factors and regional air pollutants. Results: The dataset comprises over 2.2 million adult females and males of any race/ethnicity. Over 250,000 are AANHPI females (19.6% of the female study population). Smoking status is available for over 95% of individuals. The dataset includes 7,274 lung cancer cases, including 613 cases among AANHPI females. Prevalence of never-smoking status varied greatly among AANHPI females with incident lung cancer, from 85.7% among Asian Indian to 14.4% among Native Hawaiian females. Conclusion: We have developed a large, multilevel dataset particularly well-suited to conduct prospective studies of lung cancer risk among AANHPI females who never smoked. Impact: The integrative data approach is an effective way to conduct cancer research assessing multilevel factors on cancer outcomes among small populations.

With the rapid development of smart cities, traditional street lamps have failed to meet urban development needs due to shortcomings such as low energy saving, single function, poor controllable, and management system. This article uses street lamp as the cutout for smart traffic and designs "multi-pole-in-one" multi-functional street lamp products to achieve controllable lighting, epidemic prevention and temperature measurement, advertising display and other functions to help smart city construction.

To solarize carbon capture industry and completely move away from the power plant (PP) steam cycle, a novel concept for solar-powered post-combustion carbon capture (SP-PCC) is proposed in this project. In this configuration, solvent regeneration directly occurs in a new design of “solar stripper” (So-St) network, sized and designed to replace the conventional desorption unit of the PCC. The present study evaluates the economic footprint of this SP-PCC technology in comparison with the typical PCC where the steam is totally bled from the PP steam cycle, and also the solar-assisted PCC (SA-PCC) where a portion of the steam is produced in the solar collector field (SCF) to contribute for the reboiler duty in the PCC. The CAPEX & OPEX, and the levelized cost of electricity (LCOE) is calculated for different scenarios for a 660 MWe coal-fired PP case-study located in Sydney, Australia. It is found that the LCOE of the SP-PCC is currently large and unprofitable as a result of 100% solar contribution for the thermal duty demand. However, under the same 100% solar energy contribution, the LCOE of the SA-PCC counterpart is prohibitively higher than that of the SP-PCC. Therefore, to fully solarize a carbon capture process, this novel SP-PCC would be the best technology option. Comprehensive analyses of economic parameters reveal potential areas for LCOE reductions. In order to realize the full potential of this new SP-PCC technology, future work should examine ways of leveraging on solvent thermochemical properties and process innovations. Furthermore, the enhanced sustainability aspects via preserving the steam production only for power generation must be fully addressed in a comprehensive life cycle analysis (LCA).

Osteosarcoma is the most common malignant tumor of bone predominately affecting adolescents and young adults. Viral etiology of osteosarcoma has been proposed more than a half-century ago but never been proven by identifying any virus authentically associated with human osteosarcoma. The Uyghur ethnic population in Xinjiang China has an unusually high prevalence of Kaposi’s sarcoma-associated herpesvirus (KSHV) infection and elevated incidence of osteosarcoma. In the current study, we explored the possible association of KSHV infection and osteosarcoma occurrence. Our seroepidemiological study revealed that KSHV prevalence was significantly elevated in osteosarcoma patients versus the general population in the Xinjiang Uyghur population (OR, 10.23; 95%CI, 4.25, 18.89). The KSHV DNA genome and viral latent nuclear antigen LANA were detected in most osteosarcoma tumor cells. Gene expression profiling analysis showed that KSHV positive osteosarcoma represents a distinct subtype of osteosarcomas with viral gene-driven signaling pathways that are important for osteosarcoma development. We conclude that KSHV infection is a risk factor for osteosarcoma and KSHV is associated with some osteosarcomas, representing a newly identified viral-associated endemic cancer.SignificanceViral etiology of osteosarcoma was proposed previously but has never been proven by identifying any virus that is authentically associated with human osteosarcoma. The current study revealed an association of human osteosarcoma with KSHV infection in Uyghur osteosarcoma patients. First, this study provides the first evidence that supports the possible viral etiology of human osteosarcoma. The gene expression profiling study showed that KSHV-positive osteosarcoma represents a distinct subtype of osteosarcomas, which is of diagnostic, prognostic and therapeutic significance. Second, KSHV-associated osteosarcomas preferentially occur in children and young adults, predicting that KSHV-positive children in KSHV endemic region may be at great risk for osteosarcoma. Third, the finding extended the range of human cancers associated with viruses.

Background The epidemiologic evidence from observational studies on breast cancer risk and phthalates, endocrine disrupting chemicals, has been inconsistent. In the only previous study based on pre-diagnostic urinary phthalates and risk of breast cancer, results were null in mostly white women. Methods We examined the association between pre-diagnostic urinary phthalates and breast cancer in a nested case-control study within the Multiethnic Cohort (MEC) study, presenting the first data from five major racial/ethnic groups in the USA. We measured 10 phthalate metabolites and phthalic acid, using a sensitive liquid chromatography mass spectrometry assay on 1032 women with breast cancer (48 African Americans, 77 Latinos, 155 Native Hawaiians, 478 Japanese Americans, and 274 Whites) and 1030 matched controls. Conditional logistic regression was used to examine risk with individual metabolites and ratios of primary (MEHP, mono-2-ethylhexyl-phthalate) to secondary (MEHHP, mono(2-ethyl-5-hydroxyhexyl); MEOHP, mono(2-ethyl-5-oxohexy)) metabolites of di-2-ethylhexyl phthalate (DEHP), a widely used plasticizer. In addition, we investigated risk associations with high (∑HMWP) and low molecular weight (∑LMWP) phthalates, as well as total phthalates which included high and low molecular weight phthalates with phthalic acid (∑LMHMPA) or without phthalic acid in molar ratios (∑LMHMmolar) and adjusted for creatinine and potential confounders. Results Among all women, breast cancer risk was higher for those in tertile 2 and tertile 3 of primary to secondary metabolites of DEHP (MEHP/(MEHHP + MEOHP)) in comparison to those in tertile 1; the respective odds ratios were 1.32 (95% CI 1.04–1.68) and 1.26 (95% CI 0.96–1.66) (Ptrend = 0.05). Risk among Native Hawaiian women increased with exposures to eight of ten individual phthalates and total phthalates (∑LMHMPA ORT3 vs T1 = 2.66, 95% CI 1.39–5.12, Ptrend = 0.001). In analysis by hormone receptor (HR) status, exposure above the median of ∑LMWP was associated with an increased risk of HR-positive breast cancer (OR = 1.30, 95% CI 1.05–1.60) while above the median exposure to phthalic acid was associated with an increased risk of HR-negative breast cancer (ORabove vs below median = 1.59, 95% CI 1.01–2.48). Conclusions Further investigations of suggestive associations of elevated breast cancer risk with higher ratios of primary to secondary metabolites of DEHP, and differences in risk patterns by race/ethnicity and HR status are warranted.

Background Chronic kidney disease (CKD) patients, especially those with end stage renal disease (ESRD) undergoing hemodialysis (HD), exhibit high prevalence of periodontitis. This cross-sectional study aimed to investigate the periodontal status of HD patients and its relationship with salivary microbiome. Methods One hundred eight HD patients and one hundred healthy control individuals were recruited. They were subjected to periodontal examination followed by saliva samples collection for 16S rRNA gene sequencing. Results The HD patients were with worse periodontal health status, and exhibited higher salivary microbial diversity and lower richness. The periodontal pathogens were significantly enriched in the HD patients. The inferred functional analyze showed microbes enriched in the HD patients were mainly related to metabolism. Despite the periodontal status and overall structure of the microbiome were not significantly altered as the HD duration prolonged, the abundance of Lachnospiraceae [G-2] sp. |HMT_096| is positively correlated with the duration of HD and the community periodontal index (CPI). Five OTUs (operational taxonomic units) belonging to the phyla Firmicutes were enriched as the duration prolonged, and four OTUs originated from the phyla Proteobacteria were negatively related with the CPI index. ESRD patients undergoing HD exhibited microbiota structural, compositional and functional differences compared with the healthy controls. And the species changed as the duration of hemodialysis prolonged. Conclusions End stage renal disease changes salivary microbiome and is a risk factor for oral dysbiosis.

Bladder cancer is one of the most aggressive urothelial tumors. Previous studies have suggested that epithelial-mesenchymal transition (EMT) contributes to bladder cancer progression. However, the regulatory network of EMT in bladder cancer remains elusive. In this study, we found Yin Yang 1 (YY1) is a critical regulator of EMT in bladder cancer. First, we showed that YY1 was upregulated in bladder cancer tissues than that in adjacent normal tissues. Then, we proved that YY1 promoted EMT of bladder cancer cells. Further experiments indicated that YY1 affected the EMT of bladder cancer through transforming growth factor-β (TGFβ) signaling pathway. Taken together, our study identifies YY1 as a key EMT driver in bladder cancer, suggesting it as a potential therapeutic target.

Eye tracking is a valuable topic in computer vision. Appearance-based eye tracking is a promising research direction in recent years. Convolutional neural networks (CNN) had been used in gaze estimation, which cover the significant variability in eye appearance caused by unconstrained head motion. With computation capability of consumer devices rapidly evolving, accurate and efficient appearance-based eye tracking has the potential for multipurpose applications. Person-independent networks have limit in improving gaze estimation accuracy. Person-specific network with calibration is more effective than person-independent approaches. Unlike classical eye tracking methods, appearance-based eye tracking has not a clear way to calibration. Our goal is to analyze the impact of calibration data selection and calibration target distribution on person-specific gaze estimation accuracy. We trained person-independent network and use SVR to calibration. We choose two kind of typical distribution targets to evaluation. Use different distribution targets to calibration achieves different accuracy.

A novel β-coronavirus (2019-nCoV) caused severe and even fetal pneumonia explored in a seafood market of Wuhan city, Hubei province, China, and rapidly spread to other provinces of China and other countries. The 2019-nCoV was different from SARS-CoV, but shared the same host receptor the human angiotensin-converting enzyme 2 (ACE2). The natural host of 2019-nCoV may be the batRhinolophus affinisas 2019-nCoV showed 96.2% of whole-genome identity to BatCoV RaTG13. The person-to-person transmission routes of 2019-nCoV included direct transmission, such as cough, sneeze, droplet inhalation transmission, and contact transmission, such as the contact with oral, nasal, and eye mucous membranes. 2019-nCoV can also be transmitted through the saliva, and the fetal–oral routes may also be a potential person-to-person transmission route. The participants in dental practice expose to tremendous risk of 2019-nCoV infection due to the face-to-face communication and the exposure to saliva, blood, and other body fluids, and the handling of sharp instruments. Dental professionals play great roles in preventing the transmission of 2019-nCoV. Here we recommend the infection control measures during dental practice to block the person-to-person transmission routes in dental clinics and hospitals.

More than 700 different species of bacteria, viruses, fungi, mycoplasma, and chlamydia live in the human oral cavity, collectively known as the oral microbiome. The ecological imbalance of oral microbiome can induce oral infectious diseases, such as dental caries and periodontal disease. Oral microorganisms are also closely related to tumors, diabetes, rheumatoid arthritis, cardiovascular diseases, premature delivery, and other systemic diseases, which have a significant impact on human health. So far, more than 65% of oral microbiota can be cultured in vitro. In order to better study the relationship between oral microbes and human health, several human oral microbiome collection and oral microbiome database have been established. In this chapter, the biological and pathogenic characteristics of several newly isolated oral microbes from dental plaque were introduced. Gram staining, plate culture, colony, and scanning electron microscope (SEM) images of each microorganism were also provided.

Holes are always opened in the steel tubes during the inspection and revision of initial concrete imperfections in concrete filled steel tubular (CFST) columns. The structural performance of such composite columns with holes may have obvious differences in comparison with normal CFST members. This paper intends to investigate the influences of sectional type, holes location, holes size, and holes depth on CFST stub columns. The typical failure modes, load-deformation responses, the ultimate strength, and ductility were discussed in detail. A total of twenty-eight specimens, twenty CFST columns with holes, four intact CFST specimens, and four reference hollow steel tubes subjected to axial compressive loading, were tested. The experimental results were compared with predictions of Eurocode 4 and finite element analysis. An empirical equation for predicting the ultimate strength of CFST stub columns with holes was proposed.

Highlights • ZnO/ZnS nanostructures with type-II heterojunction are successfully synthesized. • Heterojunction nanotube exhibits better sonophotocatalysis than nanorod. • Effect of morphology on piezoelectric is experimentally and simulatively studied. • Morphology engineering can affect sonophotocatalysis through turning piezoelectric., Sonophotocatalysis is one of the most significant outcomes of the exploration of the interaction between piezoelectric field and charge carriers, which exhibits potential applications in dye degradation, water splitting, and sterilization. Although several heterojunction catalysts have been applied to improve the sonophotocatalytic capability, the importance of the morphology on the sonophotocatalytic capability has not been emphasized. In this study, brush-like ZnO nanorod arrays are synthesized on a stainless-steel mesh and subsequently vulcanized into ZnO/ZnS core–shell nanorod arrays to investigate the sonophotocatalytic capability of the heterojunction. The sonophotocatalytic capability increases from 25.1% to 45.4% through vulcanization. Afterward, the ZnO/ZnS nanorods are etched to ZnO/ZnS nanotubes without affecting the crystallography and distribution of the ZnS nanoparticle shell, further improving the capability to 63.3%. The improvement can be ascribed to the coupling effect of the enhanced piezoelectric field and the reduced migration distance, which suppresses the recombination of photoexcited electron–hole pairs while transforming the morphology from nanorod to nanotube, as proven by the electron spin resonance test and numerical simulations. This study explores a novel approach of morphology engineering for enhancing the sonophotocatalytic capability of heterojunction nanoarrays.

Herein, we report on the experimental observations and a quantitative determination of the laser-induced frequency shift (LIFS) in the photoassociation (PA) spectra of spinor Bose-Einstein condensate of sodium. Our investigations revealed a nonlinear dependence of the LIFS on the intensity of PA laser. By developing a model within the quadratic Stark effect, we simulate the experimental results via a theoretical model that confirms the former. The experimental observations and the theoretical analysis can further improve the accuracy of investigations on important molecular properties and on preparation of specific molecular states, with possible applications in various key fields.

All-inorganic and lead-free CsSnI3 is emerging as one of the most promising candidates for near-infrared perovskite light-emitting diodes (NIR Pero-LEDs), which find practical applications including facial recognition, biomedical apparatus, night vision camera, and Light Fidelity. However, in the CsSnI3 -based Pero-LEDs, the holes injection is significantly higher than that of electrons, resulting in unbalanced charge injection, undesired exciton dissipation, and poor device performance. Herein, it is proposed to manage charge injection and recombination behavior by tuning the interface area of perovskite and charge-transporter. A dendritic CsSnI3 structure is prepared on the hole-transporter, only making a bottom contact with the hole-transporter and exposing all other available crystal surfaces to the electron-transporter. In other words, the interface area of perovskite/electron-transporter is significantly higher than that of perovskite/hole-transporter. Moreover, the embedding interface of perovskite/electron-transporter can spatially confine holes and electrons, increasing the radiation recombination. By taking advantage of the dendritic structure, efficient lead-free NIR Pero-LEDs are achieved with a record external quantum efficiency (EQE) of 5.4%. More importantly, the dendritic structure shows great superiorities in flexible devices, for there is almost no morphology change after 2000-cycles of bends, and the fabricated Pero-LEDs can keep 93.4% of initial EQEs after 50-cycles of bends.