Search

The flexible job shop scheduling problem has always been the focus of research in the manufacturing field. However, most of the previous studies focused more on efficiency and ignored energy consumption. Energy, especially non-renewable energy, is an essential factor affecting the sustainable development of a country. To this end, this paper designs a flexible job shop scheduling problem model with energy consideration more in line with the production field. Except for the processing stage, the energy consumption of the transport, set up, unload, and idle stage are also included in our model. The weight property of jobs is also considered in our model. The heavier the job, the more energy it consumes during the transport, set up, and unload stage. Meanwhile, this paper invents an adaptive population non-dominated sorting genetic algorithm III (APNSGA-III) that combines the dual control strategy with the non-dominated sorting genetic algorithm III (NSGA-III) to solve our flexible job shop scheduling problem model. Four flexible job shop scheduling problem instances are formulated to examine the performance of our algorithm. The results achieved by the APNSGA-III method are compared with five classic multi-objective optimization algorithms. The results show that our proposed algorithm is efficient and powerful when dealing with the multi-objective flexible job shop scheduling problem model that includes energy consumption.

Abstract Background Different confounder adjustment strategies were used to estimate odds ratios (ORs) in case-control study, i.e. how many confounders original studies adjusted and what the variables are. This secondary data analysis is aimed to detect whether there are potential biases caused by difference of confounding factor adjustment strategies in case-control study, and whether such bias would impact the summary effect size of meta-analysis. Methods We included all meta-analyses that focused on the association between breast cancer and passive smoking among non-smoking women, as well as each original case-control studies included in these meta-analyses. The relative deviations (RDs) of each original study were calculated to detect how magnitude the adjustment would impact the estimation of ORs, compared with crude ORs. At the same time, a scatter diagram was sketched to describe the distribution of adjusted ORs with different number of adjusted confounders. Results Substantial inconsistency existed in meta-analysis of case-control studies, which would influence the precision of the summary effect size. First, mixed unadjusted and adjusted ORs were used to combine individual OR in majority of meta-analysis. Second, original studies with different adjustment strategies of confounders were combined, i.e. the number of adjusted confounders and different factors being adjusted in each original study. Third, adjustment did not make the effect size of original studies trend to constringency, which suggested that model fitting might have failed to correct the systematic error caused by confounding. Conclusions The heterogeneity of confounder adjustment strategies in case-control studies may lead to further bias for summary effect size in meta-analyses, especially for weak or medium associations so that the direction of causal inference would be even reversed. Therefore, further methodological researches are needed, referring to the assessment of confounder adjustment strategies, as well as how to take this kind of bias into consideration when drawing conclusion based on summary estimation of meta-analyses.

Recently, ice with stacking disorder structure, consisting of random sequences of cubic ice (Ic) and hexagonal ice (Ih) layers, was reported to be more stable than pure Ih/Ic. Due to a much lower free energy barrier of heterogeneous nucleation, in practice, the freezing process of water is controlled by heterogeneous nucleation triggered by an external medium. Therefore, we carry out molecular dynamic simulations to explore how ice polymorphism depends on the lattice structure of the crystalline substrates on which the ice is grown, focusing on the primary source of atmospheric aerosols, carbon materials. It turns out that, during the nucleation stage, the polymorph of ice nuclei is strongly affected by graphene substrates. For ice nucleation on graphene, we find Ih is the dominant polymorph. This can be attributed to structural similarities between graphene and basal face of Ih. Our results also suggest that the substrate only affects the polymorph of ice close to the graphene surface, with the preference for Ih diminishing as the ice layer grows.

Reactive oxygen species (ROS) are produced by living cells as normal cellular metabolic byproduct. Under excessive stress conditions, cells will produce numerous ROS, and the living organisms eventually evolve series of response mechanisms to adapt to the ROS exposure as well as utilize it as the signaling molecules. ROS molecules would trigger oxidative stress in a feedback mechanism involving many biological processes, such as apoptosis, necrosis and autophagy. Growing evidences have suggested that ROS play a critical role as the signaling molecules throughout the entire cell death pathway. Overwhelming production of ROS can destroy organelles structure and bio-molecules, which lead to inflammatory response that is a known underpinning mechanism for the development of diabetes and cancer. Cytochrome P450 enzymes (CYP) are regarded as the markers of oxidative stress, can transform toxic metabolites into ROS, such as superoxide anion, hydrogen peroxide and hydroxyl radical which might cause injury of cells. Accordingly, cells have evolved a balanced system to neutralize the extra ROS, namely antioxidant systems that consist of enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidases (GPxs), thioredoxin (Trx) as well as the non-enzymatic antioxidants which collectively reduce oxidative state. Herein, we review the recent novel findings of cellular processes induced by ROS, and summarize the roles of cellular endogenous antioxidant systems as well as natural anti-oxidative compounds in several human diseases caused by ROS in order to illustrate the vital role of antioxidants in prevention against oxidative stress.

Background/Aims: Blue light emitting diodes (LEDs) have been proven to affect the growth of several types of cells. The effects of blue LEDs have not been tested on bone marrow-derived mesenchymal stem cells (BMSCs), which are important for cell-based therapy in various medical fields. Therefore, the aim of this study was to determine the effects of blue LED on the proliferation, apoptosis and osteogenic differentiation of BMSCs. Methods: BMSCs were irradiated with a blue LED light at 470 nm for 1 min, 5 min, 10 min, 30 min and 60 min or not irradiated. Cell proliferation was measured by performing cell counting and EdU staining assays. Cell apoptosis was detected by TUNEL staining. Osteogenic differentiation was evaluated by ALP and ARS staining. DCFH-DA staining and γ-H2A.X immunostaining were used to measure intracellular levels of ROS production and DNA damage. Results: Both cell counting and EdU staining assays showed that cell proliferation of BMSCs was significantly reduced upon blue LED irradiation. Furthermore, treatment of BMSCs with LED irradiation was followed by a remarkable increase in apoptosis, indicating that blue LED light induced toxic effects on BMSCs. Likewise, BMSC osteogenic differentiation was inhibited after exposure to blue LED irradiation. Further, blue LED irradiation was followed by the accumulation of ROS production and DNA damage. Conclusions: Taken together, our study demonstrated that blue LED light inhibited cell proliferation, inhibited osteogenic differentiation, and induced apoptosis in BMSCs, which are associated with increased ROS production and DNA damage. These findings may provide important insights for the application of LEDs in future BMSC-based therapies.

Effect of polyols (mannitol, sorbitol, and xylitol) at three concentrations (5, 10, and 15% w/w) on the structure of soy protein isolates (SPI) was investigated. Changes in foaming properties of SPI were then examined with the addition of polyols at different concentrations. The interactions between SPI and polyols resulted in a substantial decrease in protein surface hydrophobicity and intrinsic tryptophan fluorescence intensity, along with the covering of tyrosine. Furthermore, circular dichroism (CD) spectroscopy of SPI suggested that a more ordered and compact conformation was induced by polyols. Consequently, these structural changes led to lower foamability of SPI. An increase in the viscosity of SPI suspension seemed to be advantageous for improving the foam stability of SPI.

Functionalization of unactivated C–H bonds is an attractive strategy to introduce functionality without the need for pre-functionalized starting materials. Here the authors combine cobalt catalysis with photoredox catalysis, allowing arene-azole cross-coupling under oxidant-free conditions.

Summary: Type I interferons (IFNs) play important roles in antitumor immunity. We generated IFN-α-producing cells by genetically engineered induced pluripotent stem cell (iPSC)-derived proliferating myeloid cells (iPSC-pMCs). Local administration of IFN-α-producing iPSC-pMCs (IFN-α-iPSC-pMCs) alters the tumor microenvironment and propagates the molecular signature associated with type I IFN. The gene-modified cell actively influences host XCR1+ dendritic cells to enhance CD8+ T cell priming, resulting in CXCR3-dependent and STING-IRF3 pathway-independent systemic tumor control. Administration of IFN-α-iPSC-pMCs in combination with immune checkpoint blockade overcomes resistance to single-treatment modalities and generates long-lasting antitumor immunity. These preclinical data suggest that IFN-α-iPSC-pMCs might constitute effective immune-stimulating agents for cancer that are refractory to checkpoint blockade. : Tsuchiya et al. demonstrate that local administration of iPSC-derived myeloid cells producing interferon-α suppresses local, as well as distant, tumors. The efficacy depends on the tumor-reactive T cell response mediated by the activation of host XCR1+ dendritic cells. The concomitant use of a PD-1/PD-L1 inhibitor yields a superior antitumor effect. Keywords: cancer immunotherapy, induced pluripotent stem cells, type I interferon, XCR1, dendritic cells, cross-presentation, checkpoint blockade, PD-1, STING, CXCR3

Tumor cells reside in a highly complex and heterogeneous tumor microenvironment (TME), which is composed of a myriad of genetically stable non-cancer cells, including fibroblasts, immune cells, endothelial cells, and epithelial cells, and a tumor-specific extracellular matrix (ECM). Cancer-associated fibroblasts (CAFs), as an abundant and active stromal cell population in the TME, function as the signaling center and remodeling machine to aid the creation of a desmoplastic tumor niche. Although there is no denial that the TME and CAFs may have anti-tumor effects as well, a great deal of findings reported in recent years have convincingly revealed the tumor-promoting effects of CAFs and CAF-derived ECM proteins, enzymes, chemical factors and other downstream effectors. While there is growing enthusiasm for the development of CAF-targeting therapies, a better understanding of the complexities of CAF-ECM and CAF-cancer cell interactions is necessary before novel therapeutic strategies targeting the malignant tumor “soil” can be successfully implemented in the clinic.

Loblolly pine (Pinus taeda L.) is one of the most important species for oleoresin (a mixture of terpenoids) in South China. The high oleoresin content of loblolly pine is associated with resistance to bark beetles and other economic benefits. In this study, we conducted transcriptome analyses of loblolly pine secondary xylem to gain insight into the genes involved in terpenoid biosynthesis. A total of 372 unigenes were identified as being critical for oleoresin production, including genes for ATP-binding cassette (ABC) transporters, the cytochrome P450 (CYP) protein family, and terpenoid backbone biosynthesis enzymes. Six key genes involved in terpenoid biosynthetic pathways were selected for multiple sequence alignment, conserved motif prediction, and phylogenetic and expression profile analyses. The protein sequences of all six genes exhibited a higher degree of sequence conservation, and upstream genes were relatively more conserved than downstream genes in terpenoid biosynthetic pathways. The N-terminal regions of these sequences were less conserved than the C-terminal ends, as the N-terminals were quite diverse in both length and composition. The phylogenetic analyses revealed that most genes originated from gene duplication after species divergence, and partial genes exhibited incomplete lineage sorting. In addition, the expression profile analyses showed that all six genes exhibited high expression levels during the high-oleoresin-yielding phase.

Background: Stent-jailing and stent-jack are used for stent-assisted coil embolism (SCE) in intracranial aneurysm (IA) therapy, and cause different incidences of IA recurrence. Angiogenesis strongly correlates with aneurysm accumulation. Stent-jack causes higher mechanical forces in cerebral vessels than stent-jailing. Mechanical forces, as well as TGF-β/Smad2,3,4 signaling pathway, may play an important factor in IA recurrence by affecting angiogenesis.Methods: We explored the effects of stent-jailing or stent-jack technique on IA recurrence by investigating mechanical forces, TGF-β/Smad2,3,4 signaling pathway and the incidence of angiogenesis in IA patients. One-hundred-eighty-one IA patients were assigned into stent-jailing (n = 93) and stent-jacket groups (n = 88). The clinical outcome was evaluated using Glasgow Outcome Score (GOS) and aneurysm occlusion grades. The percentage of CD34+EPCs (releasing pro-angiogenic cytokines) in peripheral blood was measured by flow cytometer. Endothelial cells were separated from cerebral aneurysm and malformed arteries via immunomagnetic cell sorting. Angiogenesis was measured by microvessel density (MVD) using anti-CD34 monoclonal antibody staining before using the stent, immediately after surgery and 2 years later. Meanwhile, the mechanical forces in cerebral vessels were determined by measuring endothelial shear stress (ESS) via a computational method. TGF-β and Smad2,3,4 were measured by real-time qPCR and Western Blot. Tube formation analysis was performed to test the relationship between angiogenesis and TGF-β, and the effects of different techniques on angiogenesis.Results: After a 2-year follow-up, 85 and 81 patients from stent-jailing and stent-jack groups, respectively, completed the experiment. Stent-jailing technique improved GOS and reduced aneurysm occlusion grades higher than the stent-jack technique (P < 0.05). The counts of CD34+EPCs and MVD values in the stent-jailing group were lower than the stent-jack group (P < 0.05). ESS values in sent-jailing group were lower than the stent-jack group (P < 0.05), and positively correlated with MVD values (P < 0.05). TGF-β and Smad2,3,4 levels in sent-jailing group were also lower than the stent-jack group (P < 0.05). TGF-β was associated with angiogenesis incidence and stent-jack caused angiogenesis incidence more than stent-jailing.Conclusion: Stent-jailing technique reduces IA recurrence more than stent-jack by causing less mechanical forces, angiogenesis and inhibiting TGF-β/Smad2,3,4 signaling in IA patients.

Vision-based sensors such as LiDAR (Light Detection and Ranging) are adopted in the SLAM (Simultaneous Localization and Mapping) system. In the 16-beam LiDAR aided SLAM system, due to the difficulty of object detection by sparse laser data, neither the grid-based nor feature point-based solution can avoid the interference of moving objects. In an urban environment, the pole-like objects are common, invariant and have distinguishing characteristics. Therefore, it is suitable to bring more robust and reliable positioning results as auxiliary information in the process of vehicle positioning and navigation. In this work, we proposed a scheme of a SLAM system using a GNSS (Global Navigation Satellite System), IMU (Inertial Measurement Unit) and LiDAR sensor using the position of pole-like objects as the features for SLAM. The scheme combines a traditional preprocessing method and a small scale artificial neural network to extract the pole-like objects in environment. Firstly, the threshold-based method is used to extract the pole-like object candidates from the point cloud, and then, the neural network is applied for training and inference to obtain pole-like objects. The result shows that the accuracy and recall rate are sufficient to provide stable observation for the following SLAM process. After extracting the poles from the LiDAR point cloud, their coordinates are added to the feature map, and the nonlinear optimization of the front end is carried out by utilizing the distance constraints corresponding to the pole coordinates; then, the heading angle and horizontal plane translation are estimated. The ground feature points are used to enhance the elevation, pitch and roll angle accuracy. The performance of the proposed navigation system is evaluated through field experiments by checking the position drift and attitude errors during multiple two-min mimic GNSS outages without additional IMU motion constrain such as NHC (Nonholonomic Constrain). The experimental results show that the performance of the proposed scheme is superior to that of the conventional feature point grid-based SLAM with the same back end, especially in congested crossroads where slow-moving vehicles are surrounded and pole-like objects are rich in the environment. The mean plane position error during two-min GNSS outages was reduced by 38.5%, and the root mean square error was reduced by 35.3%. Therefore, the proposed pole-like feature-based GNSS/IMU/LiDAR SLAM system can fuse condensed information from those sensors effectively to mitigate positioning and orientation errors, even in a short-time GNSS denied environment.

Background/Aims: Acute myocardial infarction (AMI) is a devastating cardiovascular disease with a high rate of morbidity and mortality, partly due to enhanced arrhythmogenicity. MicroRNAs (miRNAs) have been shown to participate in the regulation of cardiac ion channels and the associated arrhythmias. The purpose of this study was to test our hypothesis that miR-223-3p contributes to the electrical disorders in AMI via modulating KCND2, the gene encoding voltage-gated channel Kv4.2 that carries transient outward K+ current Ito. Methods: AMI model was established in male Sprague-Dawley (SD) rats by left anterior descending artery (LAD) ligation. Evans blue and TTC staining was used to measure infarct area. Ito was recorded in isolated ventricular cardiomyocytes or cultured neonatal rat ventricular cells (NRVCs) by whole-cell patch-clamp techniques. Western blot analysis was employed to detect the protein level of Kv4.2 and real-time RT-PCR to determine the transcript level of miR-223-3p. Luciferase assay was used to examine the interaction between miR-223-3p and KCND2 in cultured NRVCs. Results: Expression of miR-223-3p was remarkably upregulated in AMI relative to sham control rats. On the contrary, the protein level of Kv4.2 and Ito density were significantly decreased in AMI. Consistently, transfection of miR-223-3p mimic markedly reduced Kv4.2 protein level and Ito current in cultured NRVCs. Co-transfection of AMO-223-3p (an antisense inhibitor of miR-223-3p) reversed the repressive effect of miR-223-3p. Luciferase assay showed that miR-223-3p, but not the negative control, substantially suppressed the luciferase activity, confirming the direct binding of miR-223-3p to the seed site within the KCND2 sequence. Finally, direct intramuscular injection of AMO-223-3p into the ischemic myocardium to knockdown endogenous miR-223-3p decreased the propensity of ischemic arrhythmias. Conclusions: Upregulation of miR-223-3p in AMI repressed the expression of KCND2/Kv4.2 resulting in reduction of Ito density that can cause APD prolongation and promote arrhythmias in AMI, and therefore knockdown of endogenous miR-223-3p might be considered a new approach for antiarrhythmic therapy of ischemic arrhythmias.

Background/Aims: Osteosarcoma is the second highest cause of cancer-related death in children and adolescents. Majority of osteosarcoma patients (90%) show metastasis. Previous reports revealed that osthole showed antitumor activities via induction of apoptosis and inhibition of proliferation. However, the potential effects and detailed molecular mechanisms involved remained unclear. Methods: Cell viability was analyzed by MTT assay in osteosarcoma cell lines MG-63 and SAOS-2. Cell cycle was detected by flow cytometry. The effects of migration and invasion were evaluated by wound healing assay and transwell assays. Moreover, the level of proteins expression was determined by Western blot. Results: The cell viability of MG63 and SAOS-2 were markedly inhibited by osthole in a dose- and time-dependent manner. Cell cycle was arrested and the ability of migration and invasion was obviously reduced when cells were exposed to osthole. Moreover, enzymes involved in PTEN/Akt pathway were regulated such as PTEN and p-Akt proteins. Furthermore, osthole inhibited the tumor growth in vivo. Conclusion: Our study unraveled, for the first time, the ability of osthole to suppress osteosarcoma and elucidated the regulation of PTEN/Akt pathway as a signaling mechanism for the anti-tumor action of osthole. These findings indicate that osthole may represent a novel therapeutic strategy in the treatment of osteosarcoma.

In this paper, we proposed a multi-sensor integrated navigation system composed of GNSS (global navigation satellite system), IMU (inertial measurement unit), odometer (ODO), and LiDAR (light detection and ranging)-SLAM (simultaneous localization and mapping). The dead reckoning results were obtained using IMU/ODO in the front-end. The graph optimization was used to fuse the GNSS position, IMU/ODO pre-integration results, and the relative position and relative attitude from LiDAR-SLAM to obtain the final navigation results in the back-end. The odometer information is introduced in the pre-integration algorithm to mitigate the large drift rate of the IMU. The sliding window method was also adopted to avoid the increasing parameter numbers of the graph optimization. Land vehicle tests were conducted in both open-sky areas and tunnel cases. The tests showed that the proposed navigation system can effectually improve accuracy and robustness of navigation. During the navigation drift evaluation of the mimic two-minute GNSS outages, compared to the conventional GNSS/INS (inertial navigation system)/ODO integration, the root mean square (RMS) of the maximum position drift errors during outages in the proposed navigation system were reduced by 62.8%, 72.3%, and 52.1%, along the north, east, and height, respectively. Moreover, the yaw error was reduced by 62.1%. Furthermore, compared to the GNSS/IMU/LiDAR-SLAM integration navigation system, the assistance of the odometer and non-holonomic constraint reduced vertical error by 72.3%. The test in the real tunnel case shows that in weak environmental feature areas where the LiDAR-SLAM can barely work, the assistance of the odometer in the pre-integration is critical and can effectually reduce the positioning drift along the forward direction and maintain the SLAM in the short-term. Therefore, the proposed GNSS/IMU/ODO/LiDAR-SLAM integrated navigation system can effectually fuse the information from multiple sources to maintain the SLAM process and significantly mitigate navigation error, especially in harsh areas where the GNSS signal is severely degraded and environmental features are insufficient for LiDAR-SLAM.

In this work, we study data collection in multiple unmanned aerial vehicle (UAV)-aided mobile wireless sensor networks (WSNs). The network topology is changing due to the mobility of the UAVs and the sensor nodes, so the design of efficient data collection protocols is a major concern. We address such high dynamic network and propose two mechanisms: prioritized-based contact-duration frame selection mechanism (PCdFS), and prioritized-based multiple contact-duration frame selection mechanisms (PMCdFS) to build collision-free scheduling and balance the nodes between the multi-UAV respectively. Based on the two mechanisms, we proposed a Balance algorithm to conduct the collision-free communication between the mobile nodes and the multi-UAVs. Two key design ideas for a Balance algorithm are: (a) no need of higher priority for those nodes that have lower transmission rate between them and the UAV and (b) improve the communication opportunity for those nodes that have shorter contact duration with the UAVs. We demonstrate the performance of proposed algorithms through extensive simulations, and real experiments. These experiments using 15 mobile nodes at a path with 10 intersections and 1 island, present that network fairness is efficiently enhanced. We also confirm the applicability of proposed algorithms in a challenging and realistic scenario through numerous experiments on a path at Tongji campus in Shanghai, China.

With the development of global urbanization, the Internet of Things (IoT) and smart cities are becoming hot research topics. As an emerging model, edge computing can play an important role in smart cities because of its low latency and good performance. IoT devices can reduce time consumption with the help of a mobile edge computing (MEC) server. However, if too many IoT devices simultaneously choose to offload the computation tasks to the MEC server via the limited wireless channel, it may lead to the channel congestion, thus increasing time overhead. Facing a large number of IoT devices in smart cities, the centralized resource allocation algorithm needs a lot of signaling exchange, resulting in low efficiency. To solve the problem, this paper studies the joint policy of communication and computing of IoT devices in edge computing through game theory, and proposes distributed Q-learning algorithms with two learning policies. Simulation results show that the algorithm can converge quickly with a balanced solution.

Scope: Bleeding, the main drawback of clinically used chemical anti-thrombotic drug is resulted from the unidirectional suppression of platelet activity. Therefore, dual-directional regulatory effect on platelet is the main preponderance of Panax notoginseng over these drugs. The dual-directional regulatory effect should be ascribed to the resourceful Panax notoginseng saponins (PNS). Clarifying the mechanism of main PNS in both inhibiting and promoting platelet aggregation will give a full outlook for the dual-directional regulatory effect. The present study is aimed at explaining the mechanism of Notoginsenoside Fc (Fc), a main PNS, in inhibiting platelet aggregation.Methods: In the in vitro study, after incubating platelets with Fc and m-3M3FBS, platelet aggregation was triggered by thrombin, collagen or ADP. Platelet aggregation was measured by aggregometer. Phospholipase Cγ2 (PLCγ2) and protein kinase C (PKC) activities were studied by western blotting. Diacylglycerol (DAG), thromboxane B2 (TXB2) and 1,4,5-inositol trisphosphate (IP3) concentrations were measured by corresponding ELISA kits. Calcium concentrations ([Ca2+]) were estimated through the fluorescence intensity emitted from Fluo-4. In the in vivo study, thrombus model was induced by FeCl3. The effect of Fc on thrombosis was evaluated by measurement of protein content and observation of injured blood vessel.Results: thrombin, collagen and ADP induced platelet aggregation were all suppressed by incubating platelets with Fc. Platelet PLCγ2 and subsequent DAG-PKC-TXA2 and IP3 were down-regulated by Fc as well. However, the basal [Ca2+] in platelet was not altered by Fc. Nevertheless, thrombin triggered activation of PLCγ2 and subsequent DAG-PKC-TXA2 and IP3-[Ca2+] were all abolished by Fc. Fc also attenuated platelet aggregation and PLCγ2 signaling activation induced by PLC activator, m-3M3FBS. In the in vivo study, FeCl3 induced thrombosis in rat femoral artery was significantly alleviated by administration of Fc.Conclusion: The results above suggested the antiplatelet and antithrombotic effects of Fc are carried out through oppression of PLCγ2 and subsequent DAG-PKC-TXA2 and IP3-[Ca2+]. The present study provided theoretical support for new anti-thrombotic drug exploitation by Panax notoginseng.

The aim of this study was to improve the utilization of rice straw as forage in ruminants by investigating the degradation pattern of rice straw in the dairy cow rumen. Ground up rice straw was incubated in situ in the rumens of three Holstein cows over a period of 72 h. The rumen fluid at 0 h and the rice straw at 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 h were collected for analysis of the bacterial community and the degradation of the rice straw. The bacterial community and the carbohydrate-active enzymes in the rumen fluid were analyzed by metagenomics. The diversity of bacteria loosely and tightly attached to the rice straw was investigated by scanning electron microscopy and Miseq sequencing of 16S rRNA genes. The predominant genus in the rumen fluid was Prevotella, followed by Bacteroides, Butyrivibrio, unclassified Desulfobulbaceae, Desulfovibrio, and unclassified Sphingobacteriaceae. The main enzymes were members of the glycosyl hydrolase family, divided into four categories (cellulases, hemicellulases, debranching enzymes, and oligosaccharide-degrading enzymes), with oligosaccharide-degrading enzymes being the most abundant. No significant degradation of rice straw was observed between 0.5 and 6 h, whereas the rice straw was rapidly degraded between 6 and 24 h. The degradation then gradually slowed between 24 and 72 h. A high proportion of unclassified bacteria were attached to the rice straw and that Prevotella, Ruminococcus, and Butyrivibrio were the predominant classified genera in the loosely and tightly attached fractions. The composition of the loosely attached bacterial community remained consistent throughout the incubation, whereas a significant shift in composition was observed in the tightly attached bacterial community after 6 h of incubation. This shift resulted in a significant reduction in numbers of Bacteroidetes and a significant increase in numbers of Firmicutes. In conclusion, the degradation pattern of rice straw in the dairy cow rumen indicates a strong contribution by tightly attached bacteria, especially after 6 h incubation, but most of these bacteria were not taxonomically characterized. Thus, these bacteria should be further identified and subjected to functional analysis to improve the utilization of crop residues in ruminants.

Cerebral venous thrombosis (CVT) often causes human depression, whereas depression-induced low immunity makes the patients susceptible to gastrointestinal infection. Blueberry possesses antidepressant properties which may improve autoimmunity and reduce gastrointestinal infection. Brain-derived neurotrophic factor (BDNF) performs antidepressant function and can be regulated by miR-155, which may be affected by blueberry. To explore the possible molecular mechanism, blueberry compounds were analyzed by high-performance liquid chromatography. Activity of compounds was tested by using HT22 cells. The present study tested 124 patients with CVT-induced mild-to-moderate depressive symptoms (Center for Epidemiologic Studies—Depression Scale [CES-D] ≥16) and gastrointestinal infection. Patients were randomly assigned to blueberry extract group (BG, received 10 mg blueberry extract daily) and placebo group (PG, received 10 mg placebo daily). After 3 months, depression, gastrointestinal infection and lipid profiles were investigated. Serum miR-155 and BDNF were measured using real-time quantitative polymerase chain reaction and or Western Blot. Blueberry treatment improved depressive symptoms and lipid profiles, and also reduced gastrointestinal infection in the BG group (P < 0.05) but those of the PG group (P = 1). These changes were paralleled by increase in serum levels of BDNF and miR-155 (P < 0.05). HPLC analysis showed that blueberry extracts were the main phenolic acids with 0.18, 0.85, 0.26, 0.72, 0.66, 0.4,1, and 1.92 mg/g of gentisic acid, chlorogenic acid, [2]-epicatechin, p-coumaric acid, benzoic acid, p-anisic acid, and quercetin in blueberry extracts, respectively. Phenolics in blueberry are possible causal agents in improving antidepressant activity and reducing gastrointestinal infection. Administration of blueberry increased BDNF expression and miR-155. Blueberry cannot affect BDNF level when miR-155 is overexpressed or inhibited. Phenolics from blueberry reduced gastrointestinal infection of patients with CVT by improving antidepressant activity via upregulation of miR-155-mediated BDNF.

Several case-control studies reported the relationship between single nucleotide polymorphisms (SNPs) in HSP70 genes and noise-induced hearing loss (NIHL). However, their conclusions are conflicting. This meta-analysis aims to identify the association of HSP70 variants and NIHL susceptibility.A systematical literature search was performed in PubMed, Web of Science, EMBASE, and Wanfang Chinese database. The pooled odds radio (OR), 95% confidence interval (CI) and p value were calculated in fixed- or random-effects model according to the I2 value in the heterogeneity test.Four articles containing five studies, including 633 cases and 926 controls, were included. Under the allele, homozygote and dominant model, the pooled ORs (95%CI, p-value) of rs1061581 were 1.32 (1.06-1.67, p = 0.019), 1.93 (1.10-3.36, p = 0.021) and 1.455 (1.408-2.019, p = 0.025), respectively. In addition, a significant association was found between rs2227956 in Caucasians and the NIHL susceptibility under all five genetic models. We did not discover evidence sufficient to prove the associations between the other three SNPs (rs1043618, rs2763979 and rs2075800) and the NIHL susceptibility.This meta-analysis indicated that the two HSP70 variants, rs1061581 and rs2227956, may serve as genetic susceptibility factors for NIHL. Larger scale studies are required to further update the results.

The debilitating effects of lower back pain are a major health issue worldwide. A variety of factors contribute to this, and oftentimes intervertebral disk degeneration (IDD) is an underlying cause of this disorder. Inflammation contributes to IDD, and inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β, play key roles in the pathology of IDD. Therefore, the development of treatments that inhibit the expression and/or effects of TNF-α and IL-1β in IDD patients should be a promising therapeutic approach to consider. This study characterized the potential to suppress inflammatory cytokine production in degenerative intervertebral disc (NP) cells by treatment with IL-10 and TGF-β in a canine model of IDD. IDD was induced surgically in six male beagles, and degenerative NP cells were isolated and cultured for in vitro studies on cytokine production. Cultured degenerative NP cells were divided into four experimental treatment groups: untreated control, IL-10-treated, TGF-β-treated, and IL-10- plus TGF-β-treated cells. Cultured normal NP cells served as a control group. TNF-α expression was evaluated by fluorescence activated cell sorting (FACS) analysis and enzyme-linked immunosorbent assay (ELISA); moreover, ELISA and real-time PCR were also performed to evaluate the effect of IL-10 and TGF-β on NP cell cytokine expression in vitro. Our results demonstrated that IL-10 and TGF-β treatment suppressed the expression of IL-1β and TNF-α and inhibited the development of inflammatory responses. These data suggest that IL-10 and TGF-β should be evaluated as therapeutic approaches for the treatment of lower back pain mediated by IDD.

A Global Navigation Satellite System (GNSS)/Inertial Navigation System (INS)/Light Detection and Ranging (LiDAR)-Simultaneous Localization and Mapping (SLAM) integrated navigation system based on graph optimization is proposed and implemented in this paper. The navigation results are obtained by the information fusion of the GNSS position, Inertial Measurement Unit (IMU) preintegration result and the relative pose from the 3D probability map matching with graph optimizing. The sliding window method was adopted to ensure that the computational load of the graph optimization does not increase with time. Land vehicle tests were conducted, and the results show that the proposed GNSS/INS/LiDAR-SLAM integrated navigation system can effectively improve the navigation positioning accuracy compared to GNSS/INS and other current GNSS/INS/LiDAR methods. During the simulation of one-minute periods of GNSS outages, compared to the GNSS/INS integrated navigation system, the root mean square (RMS) of the position errors in the North and East directions of the proposed navigation system are reduced by approximately 82.2% and 79.6%, respectively, and the position error in the vertical direction and attitude errors are equivalent. Compared to the benchmark method of GNSS/INS/LiDAR-Google Cartographer, the RMS of the position errors in the North, East and vertical directions decrease by approximately 66.2%, 63.1% and 75.1%, respectively, and the RMS of the roll, pitch and yaw errors are reduced by approximately 89.5%, 92.9% and 88.5%, respectively. Furthermore, the relative position error during the GNSS outage periods is reduced to 0.26% of the travel distance for the proposed method. Therefore, the GNSS/INS/LiDAR-SLAM integrated navigation system proposed in this paper can effectively fuse the information of GNSS, IMU and LiDAR and can significantly mitigate the navigation error, especially for cases of GNSS signal attenuation or interruption.

Cervical spondylotic myelopathy (CSM) is the most common cause of spinal cord dysfunction in adults in Western society. Paradoxically, relatively little is known about the pathobiological mechanisms associated with the progressive loss of neural tissue in the spinal cord of CSM patients. In this report we have utilized the twy/twy mutant mouse, which develops ossification of the ligamentum flavum at C2–C3 and exhibits progressive paralysis. This animal model represents an excellent in vivo model of CSM. This study reports novel evidence, which demonstrates that chronic extrinsic cervical spinal cord compression leads to Fas-mediated apoptosis of neurons and oligodendrocytes which is associated with activation of caspase-8, -9 and -3 and progressive neurological deficits. While surgical decompression will remain the mainstay of management of CSM, molecular therapies, which target Fas-mediated apoptosis could show promise as a complementary approach to maximize neurological recovery in this common spinal cord condition.

Background: Based on the fact that site-specific amino acid replacement on peptide antigens stimulated T cell clones to produce increased amount of IFN-γ, we investigated this structure-function relationship, using various peptide analogues. Methods: We used three human Th0 clones (BC20.7,BC33.5 and BC42.1) that express distinct TCRα and TCRβ chains, but recognize the same TCR ligand ; i.e., the same framework of peptide antigen BCGa p84-100 in the context of DRB1*1405. These T cells were stimulated with various peptide analogues, followed by determination of proliferative responses and IFN-γ production. Results: Replacement of Leu at peptide position 2 (P2) by amino acids which are less hydrophobic than the wild type (Val, Ala) or those with similar structural or neutral charge (Thr, Ser), induced increased IFN-γ production from T cells. This phenomenon was associated with structural features of TCR, especially the length of CDR3 region of TCRα. Amino acid replacement at the other positions did not induce increased IFN-γ production. Conclusions: Amino acid substitution at P2 frequently induces increased IFN-γ production in a clone-specific manner, which is associated with the structure of CDR3 in TCRVα chains.

It is well-known that many isoforms of toll-like receptors (TLRs) function as Th1 adjuvant receptors. Thus, the ligands induce Th1 differentiation in an antigen non-specific manner. During the past few years, not only Th1, but also Th2 adjuvants have been reported. Allergy-inducing materials, such as parasites, first stimulate dendritic cells (DCs) to change their character as professional antigen-presenting cells. Such a DC population (DC2) can stimulate naive CD4T cells to induce differentiation into Th2. In some instances, DCs that can stimulate regulatory T cells are also induced. Interestingly, many of such substances are glycolipids or phospholipids that mammalian species do not usually carry. In this paper, we show a cellular and molecular basis for Th2 adjuvants.

The gravity disturbance vector is one of the major error sources in high-precision and long-term inertial navigation applications. Specific to the inertial navigation systems (INSs) with high-order horizontal damping networks, analyses of the error propagation show that the gravity-induced errors exist almost exclusively in the horizontal channels and are mostly caused by deflections of the vertical (DOV). Low-frequency components of the DOV propagate into the latitude and longitude errors at a ratio of 1:1 and time-varying fluctuations in the DOV excite Schuler oscillation. This paper presents two gravity compensation methods using the Earth Gravitational Model 2008 (EGM2008), namely, interpolation from the off-line database and computing gravity vectors directly using the spherical harmonic model. Particular attention is given to the error contribution of the gravity update interval and computing time delay. It is recommended for the marine navigation that a gravity vector should be calculated within 1 s and updated every 100 s at most. To meet this demand, the time duration of calculating the current gravity vector using EGM2008 has been reduced to less than 1 s by optimizing the calculation procedure. A few off-line experiments were conducted using the data of a shipborne INS collected during an actual sea test. With the aid of EGM2008, most of the low-frequency components of the position errors caused by the gravity disturbance vector have been removed and the Schuler oscillation has been attenuated effectively. In the rugged terrain, the horizontal position error could be reduced at best 48.85% of its regional maximum. The experimental results match with the theoretical analysis and indicate that EGM2008 is suitable for gravity compensation of the high-precision and long-term INSs.

The differential electrostatic space accelerometer is an equivalence principle (EP) experiment instrument proposed to operate onboard China’s space station in the 2020s. It is designed to compare the spin-spin interaction between two rotating extended bodies and the Earth to a precision of 10−12, which is five orders of magnitude better than terrestrial experiment results to date. To achieve the targeted test accuracy, the sensitive space accelerometer will use the very soft space environment provided by a quasi-drag-free floating capsule and long-time observation of the free-fall mass motion for integration of the measurements over 20 orbits. In this work, we describe the design and capability of the differential accelerometer to test weak space acceleration. Modeling and simulation results of the electrostatic suspension and electrostatic motor are presented based on attainable space microgravity condition. Noise evaluation shows that the electrostatic actuation and residual non-gravitational acceleration are two major noise sources. The evaluated differential acceleration noise is 1.01 × 10−9 m/s2/Hz1/2 at the NEP signal frequency of 0.182 mHz, by neglecting small acceleration disturbances. The preliminary work on development of the first instrument prototype is introduced for on-ground technological assessments. This development has already confirmed several crucial fabrication processes and measurement techniques and it will open the way to the construction of the final differential space accelerometer.

Positioning, navigation, and timing (PNT) is a strategic key technology widely used in military and civilian applications. Global navigation satellite systems (GNSS) are the most important PNT techniques. However, the vulnerability of GNSS threatens PNT service quality, and integrations with other information are necessary. A chip scale atomic clock (CSAC) provides high-precision frequency and high-accuracy time information in a short time. A micro inertial measurement unit (MIMU) provides a strap-down inertial navigation system (SINS) with rich navigation information, better real-time feed, anti-jamming, and error accumulation. This study explores the coupled integration of CSAC, MIMU, and GNSS to enhance PNT performance. The architecture of coupled integration is designed and degraded when any subsystem fails. A mathematical model for a precise time aiding navigation filter is derived rigorously. The CSAC aids positioning by weighted linear optimization when the visible satellite number is four or larger. By contrast, CSAC converts the GNSS observations to range measurements by “clock coasting” when the visible satellite number is less than four, thereby constraining the error divergence of micro inertial navigation and improving the availability of GNSS signals and the positioning accuracy of the integration. Field vehicle experiments, both in open-sky area and in a harsh environment, show that the integration can improve the positioning probability and accuracy.