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In this study, to investigate the factors affecting container semitrailer rollovers while driving on interchange loop ramps, a simulation model was established in TruckSim on the basis of data collected from an in-depth investigation of the vehicle, road, and driving behaviors in a real accident. The established model was validated by reproducing the accident in a simulation. The effects of vehicle speed, the height of the cargo's center of gravity, tractor-semitrailer interactions, and the radius of the circular curve on container semitrailer rollover were investigated using the established model. The results reveal that if the height of the container semitrailer is within the limits in Chinese standards and the container semitrailer is moving at a speed of less than 45.3 km/h, it can safely travel through a loop ramp with a circular curve radius of 60 m. The height of the cargo's center of gravity and the lateral load transfer ratio have a negative relationship, and a higher center of gravity reduces the safe speed for a container semitrailer traveling through a loop ramp. During rollover, the rear axle of the semitrailer first begins to roll over and then drives the tractor to overturn.

BackgroundThe intensive care unit (ICU) is a department with a high risk of MDR bacteria, and ICU nurses and physicians play critical roles in bacterial multidrug resistance (MDR) prevention.ObjectivesTo explore the knowledge, attitudes, and practice (KAP) towards bacterial MDR among ICU nurses and physicians.MethodsA self-designed questionnaire was administered to collect data. Structural equation modeling (SEM) was applied to assess the associations among study variables.ResultsA total of 369 questionnaires were collected; 43 questionnaires were excluded due to self-contradictory on the trap question or the obviously repeated pattern. Finally, 326 (88.35%) valid questionnaires were included in the analysis. The knowledge, attitudes, and practice were 13.57 ± 1.69 (90.47%, possible range: 0-15), 38.75 ± 2.23 (96.88%, possible range: 8-40), and 47.40 ± 3.59 (94.80%, possible range: 10-50). The SEM showed that knowledge had a direct effect on attitude with a direct effect value of 0.61 (P < 0.001) and a direct negative effect on practice with a direct effect value of -0.30 (P = 0.009). The direct effect of attitude on practice was 0.89 (P < 0.001); the indirect effect of knowledge through attitude on practice was 0.52 (P < 0.001). Job satisfaction had a direct effect on attitude and practice, with an effect value of 0.52 (P = 0.030) and 0.75 (P = 0.040). Being a physician (OR = 0.354, 95%CI: 0.159-0.790, P = 0.011), 5-9.9 years of practice (OR = 4.534, 95%CI: 1.878-8.721, P < 0.001), and ≥ 10 years of practice (OR = 3.369, 95%CI: 1.301-8.721, P = 0.012) were independently associated with good knowledge. The attitude scores (OR = 1.499, 95%CI: 1.227-1.830, P < 0.001), male gender (OR = 0.390, 95%CI: 0.175-0.870, P = 0.022), and 5-9.9 years of experience (OR = 0.373, 95%CI: 0.177-0.787, P = 0.010) were independently associated with proactive practice.ConclusionNurses and physicians in the ICU showed good knowledge, positive attitudes, and proactive practice toward bacterial MDR. Nurses and physicians' knowledge had a direct effect on their attitude, while attitude might directly influence the practice and also play a mediating role between knowledge and practice. Job satisfaction might directly support the positive attitude and practice toward bacterial MDR.

Killer cell lectin-like receptor G1 (KLRG1) has traditionally been regarded as an inhibitory receptor of T cell exhaustion in chronic infection and inflammation. However, its exact role in hepatitis B virus (HBV) infection remains elusive. CD8+ T cells from 190 patients with chronic hepatitis B were analyzed ex vivo for checkpoint and apoptosis markers, transcription factors, cytokines and subtypes in 190 patients with chronic hepatitis B. KLRG1+ and KLRG1- CD8+ T cells were sorted for transcriptome analysis. The impact of the KLRG1-E-cadherin pathway on the suppression of HBV replication mediated by virus-specific T cells was validated in vitro. As expected, HBV-specific CD8+ T cells expressed higher levels of KLRG1 and showed an exhausted molecular phenotype and function. However, despite being enriched for the inhibitory molecules, thymocyte selection-associated high mobility group box protein (TOX), eomesodermin (EOMES), and Helios, CD8+ T cells expressing KLRG1 produced significant levels of tumour necrosis factor (TNF)-α, interferon (IFN)-γ, perforin, and granzyme B, demonstrating not exhausted but active function. Consistent with the in vitro phenotypic assay results, RNA sequencing (RNA-seq) data showed that signature effector T cell and exhausted T cell genes were enriched in KLRG1+ CD8+ T cells. Furthermore, in vitro testing confirmed that KLRG1-E-cadherin binding inhibits the antiviral efficacy of HBV-specific CD8+ T cells. Based on these findings, we concluded that KLRG1+ CD8+ T cells are not only a terminally exhausted subgroup but also exhibit functional diversity, despite inhibitory signs in HBV infection.

[This corrects the article DOI: 10.1371/journal.pone.0049468.].

ObjectivePreeclampsia (PE) is a severe complication of unclear pathogenesis associated with pregnancy. This research aimed to elucidate the properties of immune cell infiltration and potential biomarkers of PE based on bioinformatics analysis.Materials and methodsTwo PE datasets were imported from the Gene ExpressioOmnibus (GEO) and screened to identify differentially expressed genes (DEGs). Significant module genes were identified by weighted gene co-expression network analysis (WGCNA). DEGs that interacted with key module genes (GLu-DEGs) were analyzed further by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. The diagnostic value of the genes was assessed using receiver operating characteristic (ROC) curves and protein-protein interaction (PPI) networks were constructed using GeneMANIA, and GSVA analysis was performed using the MSigDB database. Immune cell infiltration was analyzed using the TISIDB database, and StarBase and Cytoscape were used to construct an RBP-mRNA network. The identified hub genes were validated in two independent datasets. For further confirmation, placental tissue from healthy pregnant women and women with PE were collected and analyzed using both RT-qPCR and immunohistochemistry.ResultsA total of seven GLu-DEGs were obtained and were found to be involved in pathways associated with the transport of sulfur compounds, PPAR signaling, and energy metabolism, shown by GO and KEGG analyses. GSVA indicated significant increases in adipocytokine signaling. Furthermore, single-sample Gene Set Enrichment Analysis (ssGSEA) indicated that the levels of activated B cells and T follicular helper cells were significantly increased in the PE group and were negatively correlated with GLu-DEGs, suggesting their potential importance.ConclusionIn summary, the results showed a correlation between glutamine metabolism and immune cells, providing new insights into the understandingPE pathogenesis and furnishing evidence for future advances in the treatment of this disease.

BackgroundThe RESCUE BT2 trial recently showcased the efficacy of tirofiban in treating acute ischemic stroke (AIS) without large or medium-sized vessel occlusion. To further assess the value of tirofiban from the perspectives of Chinese and US healthcare system, a study was conducted to evaluate its cost-effectiveness.MethodsA hybrid model, integrating a short-term decision tree with a long-term Markov model, was developed to assess cost-effectiveness between tirofiban and aspirin for stroke patients without large or medium-sized vessel occlusion. Efficacy data for tirofiban was sourced from the RESCUE BT2 trial, while cost information was derived from published papers. Outcomes measured included respective cost, effectiveness, and incremental cost-effectiveness ratio (ICER). We conducted a one-way sensitivity analysis to assess the robustness of the results. Additionally, we performed probabilistic sensitivity analysis (PSA) through 10,000 Monte Carlo simulations to evaluate the uncertainties associated with the results.ResultsThe study revealed that tirofiban treatment in AIS patients without large or medium-sized vessel occlusion led to a considerable reduction of 2141 Chinese Yuan (CNY) in total cost, along with a lifetime gain of 0.14 quality-adjusted life years (QALYs). In the US settings, tirofiban also exhibited a lower cost ($197,055 versus $201,984) and higher effectiveness (4.15 QALYs versus 4.06 QALYs) compared to aspirin. One-way sensitivity analysis revealed that post-stroke care costs and stroke utility had the greatest impact on ICER fluctuation in both Chinese and US settings. However, these variations did not exceed the willingness-to-pay threshold. PSA demonstrated tirofiban's superior acceptability over aspirin in over 95% of potential scenarios.ConclusionTirofiban treatment for AIS without large or medium-sized vessel occlusion appeared dominant compared to aspirin in both China and the US.

Nitrogen (N), phosphorus (P), and potassium (K) exert various effects on strawberry (Fragaria ananassa Duchesne) yields. In this study, we employed an orthogonal experimental design (T1-T9) with three fertilization treatments (N, P, and K) at three levels to identify an optimal fertilization scheme for strawberry cultivation. The effects of fertilizer combinations the rhizosphere soil microbial community were also explored by using bacterial full-length 16S rRNA and fungal ITS (internal transcribed spacer) sequencing (30 samples for each analysis). The results showed that the average plant height and leaf area of the fertilized groups were 24.6% and 41.6% higher than those of the non-fertilized group (T0). After 60 d of planting, the sucrase activity in the T6 group increased by 76.67% compared to the T0 group, with phosphate fertilizer exerting a more significant impact on sucrase activity. The T6 treatment group had the highest alpha diversity index among bacterial and fungal microorganisms, and had a different microbial community structure compared with the control group. The most abundant bacterial taxa in the strawberry rhizosphere soil were Proteobacteria, Bacteroidota, and Acidobacteriota, and the most abundant fungal phyla were Monoblepharomycota, Glomeromycota, and Mucoromycota. Application of the optimal combined fertilizer treatment (T6) significantly increased the abundance of Proteobacteria and altered the abundance of Gemmatimonas compared to other treatment groups. Notably, Gemmatimonas abundance positively correlated with strawberry plant height and soil N, P, and K levels. These findings indicated that the relative abundance of beneficial bacteria could be enhanced by the application of an optimal fertilizer ratio, ultimately improving strawberry agronomic traits.

The unique infinite self-renewal ability and multidirectional differentiation potential of stem cells provide a strong support for the clinical treatment. In light of the growing demands for stem cell storage, how to ensure personal privacy security and comply with strict ethical supervision requirements is particularly important. In order to solve the problem of low security of traditional encryption algorithm, we proposed a double encryption protection (DEP) algorithm for stem cell bank privacy data based on improved AES and chaotic encryption technology. Firstly, we presented the hash value key decomposition algorithm, through the hash value dynamic coding, cyclic shift, conversion calculation to get the key of each subsystem in the built algorithm. Secondly, DEP algorithm for privacy data is realized with two level of encryption. The first level of encryption protection algorithm used AES as the main framework, adding dynamic coding and byte filling based on DNA coding, and carries out dynamic shift of rows and simplified mixing of columns. The second level of encryption protection algorithm conducted random encoding, operation, diffusion and decoding based on the results of our proposed sequence conversion algorithm. Finally, we raised two evaluation indexes, the number of characters change rate (NCCR) and the unified average change intensity of text (UACIT) to measure the sensitivity of encryption algorithms to changes in plain information. The experimental results of using DEP shown that the average values of histogram variance, information entropy, NCCR and UACIT are116.7883, 7.6688, 32.52% and 99.67%, respectively. DEP algorithm has a large key space, high key sensitivity, and enables dynamic encryption of private data in stem cell bank. The encryption scheme provided in this study ensures the security of the private information of stem cell bank in private cloud environment, and also provides a new method for the encryption of similar high confidentiality data.

As for the problem that the traditional single depth prediction model has poor strain capacity to the prediction results of time series data when predicting lake eutrophication, this study takes the multi-factor water quality data affecting lake eutrophication as the main research object. A deep reinforcement learning model is proposed, which can realize the mutual conversion of water quality data prediction models at different times, select the optimal prediction strategy of lake eutrophication at the current time according to its own continuous learning, and improve the reinforcement learning algorithm. Firstly, the greedy factor, the fixed parameter of Agent learning training in reinforcement learning, is introduced into an arctangent function and the mean value reward factor is defined. On this basis, three Q estimates are introduced, and the weight parameters are obtained by calculating the realistic value of Q, taking the average value and the minimum value to update the final Q table, so as to get an Improved MIMO-DD-3Q Learning model. The preliminary prediction results of lake eutrophication are obtained, and the errors obtained are used as the secondary input to continue updating the Q table to build the final Improved MIMO-DD-3Q Learning model, so as to achieve the final prediction of water eutrophication. In this study, multi-factor water quality data of Yongding River in Beijing were selected from 0:00 on July 26, 2021 to 0:00 on September 5, 2021. Firstly, data smoothing and principal component analysis were carried out to confirm that there was a certain correlation between all factors in the occurrence of lake eutrophication. Then, the Improved MIMO-DD-3Q Learning prediction model was used for experimental verification. The results show that the Improved MIMO-DD-3Q Learning model has a good effect in the field of lake eutrophication prediction.

Extracting speech information from vibration response signals is a typical system identification problem, and the traditional method is too sensitive to deviations such as model parameters, noise, boundary conditions, and position. A method was proposed to obtain speech signals by collecting vibration signals of vibroacoustic systems for deep learning training in the work. The vibroacoustic coupling finite element model was first established with the voice signal as the excitation source. The vibration acceleration signals of the vibration response point were used as the training set to extract its spectral characteristics. Training was performed by two types of networks: fully connected, and convolutional. And it is found that the Fully Connected network prediction model has faster Rate of convergence and better quality of extracted speech. The amplitude spectra of the output speech signals (network output) and the phase of the vibration signals were used to convert extracted speech signals back to the time domain during the test set. The simulation results showed that the positions of the vibration response points had little effect on the quality of speech recognition, and good speech extraction quality can be obtained. The noises of the speech signals posed a greater influence on the speech extraction quality than the noises of the vibration signals. Extracted speech quality was poor when both had large noises. This method was robust to the position deviation of vibration responses during training and testing. The smaller the structural flexibility, the better the speech extraction quality. The quality of speech extraction was reduced in a trained system as the mass of node increased in the test set, but with negligible differences. Changes in boundary conditions did not significantly affect extracted speech quality. The speech extraction model proposed in the work has good robustness to position deviations, quality deviations, and boundary conditions.

Integrating urban and rural areas is the only way to achieve sustainable regional development. To comprehensively build an evaluation index system for new urbanization and rural revitalization (NU-RR), taking the Yellow River Basin (YRB) as research object, and the coupled coordination degree (CCD) model, relative development degree (RDD) model and gravity model are used to quantitatively measure the spatial and temporal patterns, synchronous development status and spatial linkages of the coupled coordination of NU-RR from 2005 to 2020. The factors influencing the CCD are identified with the help of the geographic detector model. The findings indicate that: (1) From 2005 to 2020, the combined indexes of NU-RR in the YRB show an increasing trend, while rural revitalization is growing slower than new urbanization. (2) The CCD of NU-RR in the YRB shows spatial structure characterized by "high in the east and low in the west" and undergoes an evolutionary process of "low coupling-medium coupling-high coupling". (3) The spatial disparities in the state of coupled and coordinated development of different cities are significant, mainly showing the spatial distribution characteristics dominated by the lagging new urbanization. (4) The spatial connection of CCD is networked and polarized, and the interprovincial barrier effect is weakened. (5) Total retail sales of consumer goods per capita and local general public budget expenditure as a share of GDP are the primary influencing elements affecting the CCD of NU-RR in the YRB. The interaction is manifested as bivariate enhance and nonlinear enhancement. The study's findings can guide decisions to promote high-quality urban-rural integration development in the YRB.

Two different drying methods (vacuum freeze-drying and hot-air drying) were used to dry mulberry of three varieties 'Baiyuwang'(D1), 'Longsang'(D2) and 'Zhongshen.1'(D3), and the fresh fruit of each variety was used as the control. The effects of different processing conditions on the physical characteristics, nutrients, functional components and antioxidant activity of mulberry fruit were analyzed. The results show that after different drying methods, after vacuum freeze-drying, the physical properties of dried mulberry fruit such as wettability, hygroscopic property and water retention, soluble protein, ascorbic acid and other nutrients, functional components such as polyphenols, resveratrol, chlorogenic acid and anthocyanin, and antioxidant activities such as DPPH free radical scavenging ability and ABTS free radical scavenging ability were superior to hot air drying (P < 0.01). It was concluded that vacuum freeze drying was more beneficial for retaining the original quality of mulberry than hot air drying. This study can provide a retaining theoretical basis for mulberry deep processing and comprehensive development and utilization.

Tissue slicing-assisted digestion (TSAD) of adult cardiomyocytes has shown significant improvements over conventional chunk methods. However, it remains unclear how this method compares to Langendorff perfusion, the current standard of adult cardiomyocyte isolation. Using adult Bama minipigs, we performed cardiomyocyte isolation via these two distinct methods, and compared the resulting cellular quality, including viability, cellular structure, gene expression, and electrophysiological properties, of cardiomyocytes from 3 distinct anatomical regions, namely the left ventricle, right ventricle, and left atrial appendage. Our results revealed largely indistinguishable cell quality in all of the measured parameters. These findings suggest that that TSAD can be reliably used to isolate adult mammalian cardiomyocytes as a reliable alternative to perfusion in cardiomyocyte isolation from larger mammals, particularly when Langendorff perfusion is not feasible.

The aim of this study was to investigate the influence of road factors on the safety speed threshold of a lorry turning right around a corner at a the bottom of a long downhill T-junction. Trucksim simulation software was chosen to construct a model for investigating the turning instability mechanism. A three-axle truck was chosen as the simulation vehicle and road adhesion coefficients of 0.2-0.75, road super-elevations of -2-8%, turning radii of 20-100 m, and vehicle overcharge of 0-100% selected for tuning. Simulation experiments were carried out for different bending conditions, investigating the effects of each influencing factor on the destabilization speed threshold using the control variable method. The vehicle's lateral load transfer rate and lateral acceleration were indicators for determining whether a truck was unstable. The results showed that: a) the turning radius had the most significant influence on the speed threshold for cornering instability; b) the road surface adhesion coefficient and vehicle overweight had secondary effects; and c) the road height had a general influence.

IntroductionIdentifying the technologies that will drive technological changes over the coming years is important for the optimal allocation of firms' R&D resources and the deployment of innovation strategies. The citation frequency of a patent is widely recognized as representative of the patent's value. Thus, identifying potential highly cited patents is an important goal. A number of studies have attempted to distinguish highly cited patents from others based on statistical models, but a more effective and applicable method needs to be further developed.MethodsThis paper treats the prediction of later patent citations as a classification problem and proposes a novel framework based on machine learning methods. First, a indices system to identify highly cited patents is constructed using multiple factors that are believed to influence citation frequency. Second, various machine learning models are utilized to identify highly cited patents. The optimized model with the best generalization capability is selected to predict the future impacts of newly applied patents, which may be representative of emerging significant technologies. Finally, we select the electric vehicle (EV) domain as a case study to empirically test the validity of this framework.ResultsThe optimized support vector machine (SVM) model performs well in identifying highly cited EV patents. Technological frontiers in the EV domain are identified, which are related to the topics of information systems, batteries, stability control, wireless charging, and vehicle operation.DiscussionThe good performance in prediction accuracy and generalization capability of the method proposed in this paper verifies its effectiveness and feasibility.

COVID-19 has caused negative emotional responses in patients, with significant mental health consequences for the infected population. The need for an in-depth analysis of the emotional state of COVID-19 patients is imperative. This study employed semi-structured interviews and the text mining method to investigate features in lived experience narratives of COVID-19 patients and healthy controls with respect to five basic emotions. The aim was to identify differences in emotional status between the two matched groups of participants. The results indicate generally higher complexity and more expressive emotional language in healthy controls than in COVID-19 patients. Specifically, narratives of fear, happiness, and sadness by COVID-19 patients were significantly shorter as compared to healthy controls. Regarding lexical features, COVID-19 patients used more emotional words, in particular words of fear, disgust, and happiness, as opposed to those used by healthy controls. Emotional disorder symptoms of COVID-19 patients at the lexical level tended to focus on the emotions of fear and disgust. They narrated more in relation to self or family while healthy controls mainly talked about others. Our automatic emotional discourse analysis potentially distinguishes clinical status of COVID-19 patients versus healthy controls, and can thus be used to predict mental health disorder symptoms in COVID-19 patients.

In the compressed processing of hyperspectral images, orthogonal matching pursuit algorithm (OMP) can be used to obtain sparse decomposition results. Aimed at the time-complex and difficulty in applying real-time processing, an evolutionary multi-objective optimization sparse decomposition algorithm for hyperspectral images is proposed. Instead of using OMP for the matching process to search optimal atoms, the proposed algorithm explores the idea of reference point non-dominated sorting genetic algorithm (NSGA) to optimize the matching process of OMP. Take two objective function to establish the multi-objective sparse decomposition optimization model, including the largest inner product of matching atoms and image residuals, and the smallest correlation between atoms. Utilize NSGA-III with advantage of high accuracy to solve the optimization model, and the implementation process of NSGA-III-OMP is presented. The experimental results and analysis carried on four hyperspectral datasets demonstrate that, compared with the state-of-the-art algorithms, the proposed NSGA-III-OMP algorithm has effectively improved the sparse decomposition performance and efficiency, and can effectively solve the sparse decomposition optimization problem of hyperspectral images.

With the advancements and developments in China’s tourism industry, various autonomous forms of tourism have been gaining prominence. As such, to facilitate tourists and provide them with maximum experience while economizing on time and cost is essential. One approach toward achieving this is the optimization of tourism routes. However, so far the studies on this approach have focused primarily on inland tourist sites and have lacked a geographic perspective. Therefore, this study undertook the tourism resource data of Lushunkou District of 2020, used the ArcGIS accessibility evaluation model to analyze tourism resources, and finally used the Vehicle Routing Problem of network analysis technology to optimize the tourism route of Lushunkou District and obtain the general overall intellectual framework and technical methods for tourism route optimization. The results showed that the ArcGIS accessibility evaluation model could be used to integrate resources in the tourism area before using the Vehicle Routing Problem to optimize the analysis of tourism routes, thereby enabling the separation of different types of tourism. These divisions were based on the Vehicle Routing Problem to optimize routes for one-day and two-day tours. A new method and model for optimization for tourism routes was constructed to provide a basis and reference for the optimization of tourism routes in similar cities. The observations and results of the present study can facilitate the government in developing the tourism industry and maximizing the benefits obtained from them. Further, travel agencies and tourists will have the provision of designing optimum tourism routes.

ObjectiveThe objective was to analyze the clinical characteristics and pathological characteristics of sural biopsy in nitrous oxide (N2O) -induced peripheral neuropathy.MethodsWe recruited 18 patients with N2O abuse-induced neurological disorders and reported their demographic data, clinical manifestations, laboratory examinations, and nerve conduction studies. Seven patients underwent sural nerve biopsy pathologic examination.ResultsAll 18 patients had polyneuropathy, the nerve conduction results showed significant reductions in motor and sensory amplitudes, slowing of conduction velocities, and prolongation of latencies in most tested nerves compared to the controls. Toluidine blue staining of semi-thin sections of sural nerve biopsy showed decreased myelinated nerve fiber density, increased thin myelinated nerve fiber density, and axonal regeneration. Electron microscopy showed axonal degeneration and nerve regeneration.ConclusionThe main manifestations of peripheral nerve damage caused by the abuse of N2O are lower limb weakness and distal sensory disorder. The nerve conduction study results demonstrated that mixed axonal and demyelinating neuropathy was the most common type of neuropathy. Sural biopsy showed the main pathological change was chronic axonal degeneration.

Data-nulling superimposed pilot (DNSP) effectively alleviates the superimposed interference of superimposed training (ST)-based channel estimation (CE) in orthogonal frequency division multiplexing (OFDM) systems, while facing the challenges of the estimation accuracy and computational complexity. By developing the promising solutions of deep learning (DL) in the physical layer of wireless communication, we fuse the DNSP and DL to tackle these challenges in this paper. Nevertheless, due to the changes of wireless scenarios, the model mismatch of DL leads to the performance degradation of CE, and thus faces the issue of network retraining. To address this issue, a lightweight transfer learning (TL) network is further proposed for the DL-based DNSP scheme, and thus structures a TL-based CE in OFDM systems. Specifically, based on the linear receiver, the least squares estimation is first employed to extract the initial features of CE. With the extracted features, we develop a convolutional neural network (CNN) to fuse the solutions of DL-based CE and the CE of DNSP. Finally, a lightweight TL network is constructed to address the model mismatch. To this end, a novel CE network for the DNSP scheme in OFDM systems is structured, which improves its estimation accuracy and alleviates the model mismatch. The experimental results show that in all signal-to-noise-ratio (SNR) regions, the proposed method achieves lower normalized mean squared error (NMSE) than the existing DNSP schemes with minimum mean square error (MMSE)-based CE. For example, when the SNR is 0 decibel (dB), the proposed scheme achieves similar NMSE as that of the MMSE-based CE scheme at 20 dB, thereby significantly improving the estimation accuracy of CE. In addition, relative to the existing schemes, the improvement of the proposed scheme presents its robustness against the impacts of parameter variations.

Obesity is closely associated with non-alcoholic fatty liver disease (NAFLD), and elevated serum palmitate is the link between obesity and excessive hepatic lipid accumulation. Forkhead box O-1 (FoxO1) is one of the FoxO family members of transcription factors and can stimulate adipose triglyceride lipase (ATGL) and suppress its inhibitor G0/G1 switch gene 2 (G0S2) expression in the liver. However, previous researches have also shown conflicting results regarding the role of FoxO1 in hepatic lipid accumulation. We therefore examined the role of FoxO1 as a downstream suppressor to palmitate-stimulated hepatic steatosis. Palmitate significantly promoted lipid accumulation but inhibited lipid decomposition in human HepG2 hepatoma cells. Palmitate also significantly reduced FoxO1, ATGL and its activator comparative gene identification-58 (CGI-58) expression but increased peroxisome proliferator-activated receptorγ (PPARγ) and its target gene G0S2 expression. FoxO1 overexpression significantly increased palmitate-inhibited ATGL and CGI-58 expression but reduced palmitate-stimulated PPARγ and its target gene G0S2 expression. FoxO1 overexpression also inhibited lipid accumulation and promoted lipolysis in palmitate-treated hepatocytes. Overall, these results indicate that FoxO1-mediated ATGL-dependent lipolysis may be an effective molecular mechanism in protecting hepatocytes from palmitate-induced fat accumulation.

ObjectiveTo study the epidemiology and outcomes of delirium among hospitalized patients in Zambia.MethodsWe conducted a prospective cohort study at the University Teaching Hospital in Lusaka, Zambia, from October 2017 to April 2018. The primary exposure was delirium duration over the initial 3 days of hospitalization, assessed daily using the Brief Confusion Assessment Method. The primary outcome was 6-month mortality. Secondary outcomes included 6-month disability, evaluated using the World Health Organization Disability Assessment Schedule 2.0.Findings711 adults were included (median age, 39 years; 461 men; 459 medical, 252 surgical; 323 with HIV). Delirium prevalence was 48.5% (95% CI, 44.8%-52.3%). 6-month mortality was higher for delirious participants (44.6% [39.3%-50.1%]) versus non-delirious participants (20.0% [15.4%-25.2%]; P < .001). After adjusting for covariates, delirium duration independently predicted 6-month mortality and disability with a significant dose-response association between number of days with delirium and odds of worse clinical outcome. Compared to no delirium, presence of 1, 2 or 3 days of delirium resulted in odds ratios for 6-month mortality of 1.43 (95% CI, 0.73-2.80), 2.20 (1.07-4.51), and 3.92 (2.24-6.87), respectively (P < .001). Odds of 6-month disability were 1.20 (0.70-2.05), 1.73 (0.95-3.17), and 2.80 (1.78-4.43), respectively (P < .001).ConclusionAmong hospitalized medical and surgical patients in Zambia, delirium prevalence was high and delirium duration independently predicted mortality and disability at 6 months. This work lays the foundation for prevention, detection, and management of delirium in low-income countries. Long-term follow up of outcomes of critical illness in resource-limited settings appears feasible using the WHO Disability Assessment Schedule.

Root growth potential (RGP) is a popular physiological indicator used to evaluate seedling vigor. However, the time scale used in the RGP test is the order of days, which leads to poor performance of the RGP method. We propose an optical interference method, called statistical interferometry, to measure minute root elongation at a sub-nanometer scale, which can decrease the time used in measuring RGP. The time scale of this method is also 104 times less than that of the RGP method. Because we can measure the length of root elongation continuously, we can compute the root elongation rate (RER), which is the variety of the length of root elongation per second. Continuous monitoring can help determine the quality of Masson pine seedling as soon as possible. To show the effectiveness of our proposed method, we designed an experiment, in which we applied different water stresses to our collected Masson pine seedlings and acquired two groups of pines, representing two different qualities: one stressed by water and one not. After measuring the RER of the groups in our experiments, we found that RER is interrelated with the quality of seedlings.

BackgroundWorkplace experience, defined as the evaluation of the work environment and performance, and a characteristic of workplace culture, can influence an employee's work-life balance. Most carer-employees, who combine paid full-time work and informal caregiving responsibilities, struggle to maintain a healthy work-life balance. Caregiver-Friendly Workplace Programs are designed to improve the work experience, and ultimately, the work-life balance of carer-employees. The purpose of this study is to identify changes in workplace culture through the examination of the efficacy of a caregiver-friendly workplace program on workplace experience. First, we identify whether awareness of a caregiver-friendly workplace program directly increases the amount of work support received and, in turn, improves workplace experience. Second, we will examine if significant differences in the amount of work support received translates into an improved workplace experience for carer-employees over time.MethodsTwo university-wide online surveys were conducted separately; time 1 (T1) during the summer of 2015, and time 2 (T2), in the summer of 2017. In each survey, nearly 7000 employees received the invitation to participate with a response rate ranging 10% (T1) to 12% (T2). Respondents were asked about their sociodemographic characteristics, caregiving responsibilities (if applicable), awareness of caregiver-friendly workplace program, types of work support received, and work experience. Reliability analyses was conducted for three scales: awareness of caregiver-friendly workplace program; work support, and; workplace experience. Proportional T-tests were used to examine the difference amongst the intervention scales over time. Structural equation modeling (SEM), via path analysis, was used to investigate the causal indirect (awareness of caregiver-friendly workplace program to work support to workplace experience) relationship that define the workplace culture.ResultsNo significant changes in workplace culture were found over time. However, awareness of caregiver-friendly workplace programs is shown to positively impact the amount of support received, which sequentially improves workplace experience, and ultimately workplace culture. This therefore suggests that the implementation of caregiver-friendly workplace programs is potentially effective.ConclusionsResults suggest that amount of support received, and workplace experience would be better reassessed via a longer time period (i.e., 5 yr. window), and improved support for managers and supervisors is needed to supplement relationships with their employees.

Evidence link bacterial enterotoxins to apparent crypt-cell like cells (CCLCs), and Alpha Defensin 5 (DEFA5) expansion in the colonic mucosa of Crohn's colitis disease (CC) patients. These areas of ectopic ileal metaplasia, positive for Paneth cell (PC) markers are consistent with diagnosis of CC. Retrospectively, we: 1. Identified 21 patients with indeterminate colitis (IC) between 2000-2007 and were reevaluation their final clinical diagnosis in 2014 after a followed-up for mean 8.7±3.7 (range, 4-14) years. Their initial biopsies were analyzed by DEFA5 bioassay. 2. Differentiated ulcer-associated cell lineage (UACL) analysis by immunohistochemistry (IHC) of the CC patients, stained for Mucin 6 (MUC6) and DEFA5. 3. Treated human immortalized colonic epithelial cells (NCM460) and colonoids with pure DEFA5 on the secretion of signatures after 24hr. The control colonoids were not treated. 4. Treated colonoids with/without enterotoxins for 14 days and the spent medium were collected and determined by quantitative expression of DEFA5, CCLCs and other biologic signatures. The experiments were repeated twice. Three statistical methods were used: (i) Univariate analysis; (ii) LASSO; and (iii) Elastic net. DEFA5 bioassay discriminated CC and ulcerative colitis (UC) in a cohort of IC patients with accuracy. A fit logistic model with group CC and UC as the outcome and the DEFA5 as independent variable differentiator with a positive predictive value of 96 percent. IHC staining of CC for MUC6 and DEFA5 stained in different locations indicating that DEFA5 is not co-expressed in UACL and is therefore NOT the genesis of CC, rather a secretagogue for specific signature(s) that underlie the distinct crypt pathobiology of CC. Notably, we observed expansion of signatures after DEFA5 treatment on NCM460 and colonoids cells expressed at different times, intervals, and intensity. These factors are key stem cell niche regulators leading to DEFA5 secreting CCLCs differentiation 'the colonic ectopy ileal metaplasia formation' conspicuously of pathogenic importance in CC.

[This corrects the article DOI: 10.1371/journal.pone.0228391.].

BACKGROUND:The respiratory syncytial virus (RSV) is the main cause of bronchiolitis in infants and interferon (IFN) α is a commercial antiviral drug. The nebulization of IFN α1b could be a viable treatment method. In this study, the therapeutic effects and safety of IFN α1b delivery via nebulization in infant bronchiolitis were investigated in this multi-center prospective study. METHODS AND FINDINGS:Bronchiolitis patients admitted to 22 hospitals who met the inclusion criteria were enrolled and randomly allocated to four groups: control, IFN Intramuscular Injection, IFN Nebulization 1 (1 μg/kg), and IFN Nebulization 2 (2 μg/kg) groups. All patients were observed for 7 days. The therapeutic effects and safety of different IFN delivery doses and delivery modes were evaluated. Coughing severity change, as scored by the researchers and parents, between days 1 and 3 was significantly different between the IFN Nebulization 2 and control groups. Lowell wheezing score change between days 3 and 5 was significantly different between IFN Nebulization 1 and control groups. There were no significant differences among the four groups regarding the number of consecutive days with fever, three-concave sign, fatigue and sleepiness, and loss of appetite. There were no cases of severe complications, no recurrence of fever, and no regression of mental status. CONCLUSIONS:IFN-α1b could more effectively alleviate coughing and wheezing in bronchiolitis. IFN-α1b nebulization had significant advantages in shortening the duration of wheezing and alleviating coughing.

Previously, applications of intensity analysis (IA) on land use and land cover change (LULCC) studies have focused on deviations from uniform intensity (UI) and failed to quantify the reasons behind these deviations. This study presents the application of IA with hypothetical errors that could explain non-uniform LULCC in the context of IA at four-time points. LULCC in the Ashi watershed was examined using Landsat images from 1990, 2000, 2010 and 2014 showing the classes: Urban, water, agriculture, close canopy, open canopy and other vegetation. Matrices were created to statistically examine LULCC using IA. The results reveal that the seeming LULCC intensities are not uniform with respect to the interval, category and transition levels of IA. Error analysis indicates that, hypothetical errors in 13%, 19% and 11.2% of the 2000, 2010 and 2014 maps respectively could account for all differences between the observed gain intensities and the UI; while errors in 12%, 21%, and 11% of the 1990, 2000 and 2010 maps respectively could account for all differences between the observed loss intensities and the UI. A hypothetical error in 0.6% and 1.6% of the 1990 map; 1.5% and 4% of the 2000 map; 1.2% and 2.1% of the 2010 map could explain divergences from uniform transitions given URB gain and AGR gain during 1990-2000, 2000-2010 and 2010-2014 respectively. Evidence for a specific deviation from the relevant hypothesized UI is either strong or weak depending on the size of these errors. We recommend that users of IA concept consider assessing their map errors, since limited ground information on past time point data exist. These errors will indicate strength of evidence for deviations and reveals patterns that increase researcher's insight on LULCC processes.

Sea buckthorn (Hippophae rhamnoides) is an ecologically and economically important species. Here, we assessed the diversity of 78 accessions cultivated in northern China using 8 agronomic characteristics, oil traits (including oil content and fatty acid composition) in seeds and fruit pulp, and SSR markers at 23 loci. The 78 accessions included 52 from ssp. mongolica, 6 from ssp. sinensis, and 20 hybrids. To assess the phenotypic diversity of these accessions, 8 agronomic fruit traits were recorded and analyzed using principal component analysis (PCA). The first two PCs accounted for approximately 78% of the variation among accessions. The oil contents were higher in pulp (3.46-38.56%) than in seeds (3.88-8.82%), especially in ssp. mongolica accessions. The polyunsaturated fatty acid (PUFA) ratio was slightly lower in the seed oil of hybrids (76.06%) than that of in ssp. mongolica (77.66%) and higher than that of in ssp. sinensis (72.22%). The monounsaturated fatty acid (MUFA) ratio in the pulp oil of ssp. sinensis (57.00%) was highest, and that in ssp. mongolica (51.00%) was equal to the ratio in the hybrids (51.20%). Using canonical correspondence analysis (CCA), we examined the correlation between agronomic traits and oil characteristics in pulp and seeds. Oil traits in pulp from different origins were correlated with morphological groupings (r = 0.8725, p = 0.0000). To assess the genotypic diversity, 23 SSR markers (including 17 loci previously reported) were used among the 78 accessions with 59 polymorphic amplified fragments obtained and an average PIC value of 0.2845. All accessions were classified into two groups based on the UPGMA method. The accessions of ssp. sinensis and ssp. mongolica were genetically distant. The hybrid accessions were close to ssp. mongolica accessions. The 8 agronomic traits, oil characteristics in seed and pulp oils, and 23 SSR markers successfully distinguished the 78 accessions. These results will be valuable for cultivar identification and genetic diversity analysis in cultivated sea buckthorn.

The liquid foodstuffs such as edible oil products remain a problem of excessive aflatoxin B1 (AFB1) content. This paper focused on the preparation of magnetic mesoporous silica (MMS) from rice husk ash for the removal of AFB1 in oil system. The MMS preparation process, adsorption conditions, structural characteristics, and adsorption mechanism were investigated. The optimum conditions for MMS preparation were pH 11.0 and 80°C for 24 h. The characterization results showed that magnetic particles were successfully embedded in the MMS and had high responsiveness to a magnetic field, which was advantageous for recyclability. The MMS had ordered uniform channels with a specific surface area of 730.98 m2/g and pore diameter of 2.43 nm. The optimum adsorption conditions were 2 h at 20°C. For AFB1 with an initial concentration of 0.2 μg/mL, the MMS adsorption capacity was 171.98 μg/g and the adsorption rate was 94.59%. The MMS adsorption isotherm fitted the Langmuir model well under the assumption of monolayer AFB1 adsorption with uniformly distributed adsorption sites on the MMS surface. The maximum amount of AFB1 adsorbed according to the Langmuir isotherm was 1118.69 μg/g. A quasi-second-order kinetic model gave a better fit to the process of AFB1 adsorption on MMS. The values of ΔH (-19.17 kJ/mol) and ΔG (-34.09, -34.61, and -35.15 kJ/mol at 283, 293, and 303 K, respectively) were negative, indicating that AFB1 adsorption on MMS was a spontaneous exothermic process. The results indicated that MMS was a promising material for AFB1 removal in oil system, and this study will serve as a guide for practical MMS applications.

The early detection and differential diagnosis of respiratory infections increase the chances for successful control of COVID-19 disease. The nucleic acid RT-PCR test is regarded as the current standard for molecular diagnosis. However, the maximal specificity confirmation target ORF1ab gene is considered to be less sensitive than other targets in clinical application. In addition, recent evidence indicated that the initial missed diagnosis of asymptomatic patients with SARS-CoV-2 and discharged patients with "re-examination positive" might be due to low viral load, and the ability of rapid mutation of SARS-CoV-2 also increases the rate of false-negative results. Moreover, the mixed sample nucleic acid detection is helpful in seeking out the early community transmission of SARS-CoV-2 rapidly, but the detection kit needs ultra-high detection sensitivity. Herein, the lowest detection concentration of different nucleic acid detection kits was evaluated and compared to provide direct evidence for the selection of kits for mixed sample detection or make recommendations for the selection of validation kit, which is of great significance for the prevention and control of the current epidemic and the discharge criteria of low viral load patients.

In this paper, the interaction strategies and the evolutionary game analysis of the actions taken by the government and the public in the early days of the epidemic are incorporated into the natural transmission mechanism model of the epidemic, and then the transmission frequency equations of COVID-19 epidemic is established. According to the cumulative confirmed cases of COVID-19 in the UK and China, the upper limit of the spread of COVID-19 in different evolutionary scenarios is set. Using SPSS to perform logistic curve fitting, the frequency fitting equations of cumulative confirmed cases under different evolution scenarios are obtained respectively. The analysis result shows that the emergency response strategy adopted by the government in the early days of the epidemic can effectively control the spread of the epidemic. Combined with the transmission frequency equation of COVID-19 epidemic, measures taken by the government are analyzed. The influence of each measure on the frequency variable is judged and then the influence on the spread of the epidemic is obtained. Finally, based on the above analysis, the government is advised to adhere to the principles of scientific, initiative and flexibility when facing major epidemics.

Small cell lung cancer (SCLC) is a carcinoma of the lungs with strong invasion, poor prognosis and resistant to multiple chemotherapeutic drugs. It has posed severe challenges for the effective treatment of lung cancer. Therefore, searching for genes related to the development and prognosis of SCLC and uncovering their underlying molecular mechanisms are urgent problems to be resolved. This study is aimed at exploring the potential pathogenic and prognostic crucial genes and key pathways of SCLC via bioinformatic analysis of public datasets. Firstly, 117 SCLC samples and 51 normal lung samples were collected and analyzed from three gene expression datasets. Then, 102 up-regulated and 106 down-regulated differentially expressed genes (DEGs) were observed. And then, functional annotation and pathway enrichment analyzes of DEGs was performed utilizing the FunRich. The protein-protein interaction (PPI) network of the DEGs was constructed through the STRING website, visualized by Cytoscape. Finally, the expression levels of eight hub genes were confirmed in Oncomine database and human samples from SCLC patients. It showed that CDC20, BUB1, TOP2A, RRM2, CCNA2, UBE2C, MAD2L1, and BUB1B were upregulated in SCLC tissues compared to paired adjacent non-cancerous tissues. These suggested that eight hub genes might be viewed as new biomarkers for prognosis of SCLC or to guide individualized medication for the therapy of SCLC.

Faced with the scarcity of water resource and irrational fertilizer use, it is highly important to supply plants with water and fertilizer at desiderated stages to improve yield with high water use efficiency (WUE). A pot experiment was conducted to investigate the effects of growth stage-specific water deficiency and potassium (K) fertilization on tomato yield and WUE. The entire growing season of tomato was divided into 5 stages: vegetative growth stage (VG), flowering and fruit setting stage (FS), early fruit growth stage (FG), fruit development stage (FD) and fruit maturity stage (FM). Three soil moisture (W) and three K fertilization levels were set up. W levels included W1, W2 and W3, indicating that soil water was maintained at 60-70% field capacity, 70-80% field capacity, and 80-90% field capacity, respectively. K levels included K1, K2 and K3, indicating that 0 g K2O per kg soil, 0.46 g K2O per kg soil and 0.92 g K2O per kg soil was applied. All combinations of the three W and three K levels were solely imposed at each of the five growth stages, for other four stages, plants were watered to 80-90% field capacity without K fertilizer (W3K1). The permanent W3K1 over the entire growth stage was taken as control (CK). The results showed that W deficiency imposed at all stages significantly affected tomato yield (P

Salt stress is one of the major environmental constraints for the production and yield of grape (Vitis vinifera) worldwide. The SOS3 gene family is part of the Salt Overly Sensitive (SOS) signaling pathway, a well-defined signaling pathway known to play a role in plant response to salt stress. In this study, the grapevine SOS3 gene family was annotated and the role of the annotated genes in salinity stress response was characterized. Nine grapevine SOS3 genes was identified in the grapevine genome and was subsequently analyzed. The expression patterns of the nine VviSOS3 genes, as determined by reverse transcription quantitative PCR (RT-qPCR), varied greatly in leaves, roots, and stems of in-vitro grown Pinot noir grapevine cultivar(PN40024) in response to salt (250mM NaCl) and polyethylene glycol 6000 (PEG, osmolality equal to the salt treatment) treatments over a 36h time period. All of the VviSOS3 genes, except VviSOS3.7, were up-regulated in leaves in response to the salt and PEG treatments. The majority of VviSOS3 genes, except VviSOS3.8 were up-regulated in roots in response to the PEG stress, with an opposite expression pattern in the root and stem in response to salt stress. The salinity treatment decreased the soluble protein content. Based on the expression pattern and physiological data, VviSOS3.7 and VviSOS3.8 were identified as candidate genes for further functional characterizations regarding their role in the response of grapevine to salt stress.

The internal environment of the gallbladder has been considered extremely unfavorable for bacterial growth, and the microbial profile of the gallbladder still unknown. By high-throughput sequencing of the bacterial 16S rRNA gene, we studied the microbial profile of the gallbladder from healthy rabbits before and after weaning. Moreover, we investigated the difference of microbiota between the gallbladder and gut. Our results showed that the gallbladder was dominantly populated by Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria in the phylum throughout the developmental stages of rabbits. The adult rabbits showed higher species richness and exhibited higher bacterial diversity than rabbits before weaning based on the results of alpha diversity. Beta diversity analyses indicated differences in the bacterial community composition between different developmental stages. In the comparison of the gallbladder and feces, Firmicutes and Bacteroidetes were dominant in the phylum, as they were present in about 61% and 21% of the feces, respectively. Conversely, in the gallbladder, Firmicutes was the most dominant (about 41%), and Bacteroidetes and Proteobacteria were present in about 16% and 22% of the gallbladder, respectively. The Unweighted UniFrac Principal Coordinate Analysis results illustrated samples clustered into 2 categories: the gallbladder and feces. Our study might provide a foundation for knowledge on gallbladder microbiota for the first time and a basis for further studies on gallbladder and intestinal health.

At the time of this study, prior to the introduction of biologics in the US, systemic therapies used for the treatment of moderate-to-severe atopic dermatitis included off-label immunosuppressants and corticosteroids. Immunosuppressant therapy is associated with a substantial risk of side-effects, therefore needing clinical monitoring, and is likely to incur a significant healthcare burden for patients and payers. This retrospective cohort study based on claims data measured immunosuppressant use and its associated burden among US adult patients with atopic dermatitis covered under commercial or Medicare Supplemental insurance from January 01, 2010, to September 30, 2015. Overall, based on age, gender, region, and index year, 4201 control patients with atopic dermatitis without immunosuppressant use were matched with 4204 patients treated with immunosuppressants. The majority (68.5%) of patients using immunosuppressants were non-persistent with immunosuppressant treatment during the 12-month follow-up period after a mean (standard deviation) of 88.1 (70.7) days of immunosuppressant use; 72.3% required systemic steroid rescue treatment. Immunosuppressant users had higher incidence of immunosuppressant-related clinical events than controls; in addition, a larger proportion of immunosuppressant users versus controls developed cancer (0.28% vs 0.14%, respectively; P < 0.0001). Healthcare utilization and costs associated with clinical events and monitoring were also higher for immunosuppressant users compared with controls (total costs, $9516 vs $1630, respectively; P < 0.0001; monitoring costs, $363 vs $54, respectively; P < 0.0001). This study revealed that patients treated with systemic immunosuppressants often require systemic steroids or changes to treatment. The increase in immunosuppressant-related clinical events, including the need for increased monitoring with immunosuppressant treatment, compared with controls demonstrates a substantial treatment burden and highlights the unmet need for more effective long-term therapies for atopic dermatitis with improved safety profiles and reduced monitoring requirements.

Electron-beam irradiation (EBI) is a cold sterilization technology used in the irradiation processing of food, including rice. Herein, the effects of EBI on the swelling power, color, pasting, and sensory properties of white rice after short-term storage were analyzed. Samples were electron-beam irradiated at 0, 2, 4, 6, or 8 kGy and stored at 25 °C or 37 °C for up to 75 days. Results showed that swelling power and major pasting viscosities (including peak, breakdown, and setback viscosities) at both storage temperatures decreased with increased irradiation dose. Negative correlations were also observed between the major viscosities of pasting properties and irradiation dose at both storage temperatures. During sensory evaluation, extremely low scores for rice hardness, appearance, taste, and overall acceptability were obtained for rice subjected to high EBI dose (>4 kGy). However, rice stored at 37 °C showed lower performance than rice at 25 °C in terms of the abovementioned parameters. By contrast, the sensory properties at irradiation doses between 2 and 4 kGy were better than those of the control group at both storage temperatures. All these findings indicated the potential of low-dose (

PurposeThe aim of this study was to investigate the effect of phosphotyrosine interaction domain containing 1 (PID1) on the insulin-induced activation of the AKT (protein kinase B)/protein kinase A (PKA)/hormone-sensitive lipase (HSL) pathway and lipolysis.MethodsSprague-Dawley rats were fed either chow or a high-fat diet (HFD). The levels of insulin, glycerol, free fatty acids (FFAs) and PID1 mRNA expression were measured in the 2 groups. Furthermore, we examined the role of PID1 in the regulation of the AKT/PKA/HSL cascade and lipolysis in the 3T3-L1 cell line.ResultsAdipose tissue from HFD rats exhibited elevated PID1 expression, which showed a positive correlation with insulin levels and lipolysis. In 3T3-L1 adipocytes, we found that the antilipolytic effect of insulin is mediated by AKT and that phosphorylated AKT results in the promotion of PDE3B expression, the dephosphorylation of PKA and HSL and the suppression of glycerol release. However, overexpression of PID1 and treatment with 1 μM isoproterenol and 100 nM insulin for 24 h resulted in an increased release of glycerol and a noticeable inhibition of AKT phosphorylation, PDE3B expression and the phosphorylation of PKA/HSL in 3T3-L1 cells. In contrast, knockdown of PID1 and treatment with the above reagents inhibited lipolysis and activated the phosphorylation of AKT, which resulted in the dephosphorylation of PKA and HSL.ConclusionsOur findings indicate that PID1 in adipose tissue increases lipolysis by altering the antilipolytic action of insulin. This suggests that PID1 may represent a new therapeutic target to ameliorate adipocyte lipolysis and hence improve insulin sensitivity.

[This corrects the article DOI: 10.1371/journal.pone.0214606.].

[This corrects the article DOI: 10.1371/journal.pone.0104282.].

The performance of three machine learning methods (support vector regression, random forests and artificial neural network) for estimating the LAI of paddy rice was evaluated in this study. Traditional univariate regression models involving narrowband NDVI with optimized band combinations as well as linear multivariate calibration partial least squares regression models were also evaluated for comparison. A four year field-collected dataset was used to test the robustness of LAI estimation models against temporal variation. The partial least squares regression and three machine learning methods were built on the raw hyperspectral reflectance and the first derivative separately. Two different rules were used to determine the models' key parameters. The results showed that the combination of the red edge and NIR bands (766 nm and 830 nm) as well as the combination of SWIR bands (1114 nm and 1190 nm) were optimal for producing the narrowband NDVI. The models built on the first derivative spectra yielded more accurate results than the corresponding models built on the raw spectra. Properly selected model parameters resulted in comparable accuracy and robustness with the empirical optimal parameter and significantly reduced the model complexity. The machine learning methods were more accurate and robust than the VI methods and partial least squares regression. When validating the calibrated models against the standalone validation dataset, the VI method yielded a validation RMSE value of 1.17 for NDVI(766,830) and 1.01 for NDVI(1114,1190), while the best models for the partial least squares, support vector machine and artificial neural network methods yielded validation RMSE values of 0.84, 0.82, 0.67 and 0.84, respectively. The RF models built on the first derivative spectra with mtry = 10 showed the highest potential for estimating the LAI of paddy rice.

BACKGROUND:There is no consensus regarding the relationship between HBV DNA and liver fibrosis, and the relationship between HBV DNA and the degree of liver cirrhosis has not been reported in patients with chronic HBV infection. METHODS:From January 2011 to December 2016, liver biopsies were performed on 396 patients with chronic hepatitis B and cirrhosis. Assessments of liver fibrosis and cirrhosis were based on the Laennec staging system. RESULTS:Serum levels of HBV DNA were correlated with fibrosis and cirrhosis (KW = 73.946, P

Saline-alkali soil is an arable land resource on which transgenic Bacillus thuringiensis (Bt) cotton has been planted on a large scale in accordance with food security strategies. There are, however, concerns about the insecticidal effects of Bt cotton on target insect pests. In this study, a Bt cotton variety, GK19, and its nontransgenic parent variety, Simian-3, were used as experimental models for investigating the effect of the expression of exogenous insecticidal proteins in Bt cotton under NaCl stress on the feeding behavior and nutritional parameters of Helicoverpa armigera. The results showed that the expression of exogenous insecticidal proteins in GK19 was significantly inhibited under NaCl stress. However, the feeding, crawling, resting and spinning down behavior of the 5th instar H. armigera larvae on GK19 Bt cotton, as well as the amount of food consumed and feces produced by these larvae, did not markedly differ under different NaCl concentrations. In contrast, the mean relative growth rate (MRGR), relative growth rate (RGR), approximate digestibility (AD), efficiency of conversion of ingested food (ECI) and efficiency of conversion of digested food (ECD) of the larvae markedly decreased in response to NaCl stress. Under the same concentration of NaCl, the nutritional parameters of the bollworm larvae on GK19 Bt cotton or Simian-3 nontransgenic cotton were different. However, the interaction between salt stress and cotton variety had no significant effect on the feeding behavior or nutritional parameters of H. armigera larvae. These results may provide a scientific basis for determining the effect of exogenous insecticidal protein expression in Bt cotton under NaCl stress on H. armigera and can therefore be useful for the effective application of Bt cotton in saline-alkali soils to prevent and control H. armigera.

An effective method for research of macro-morphological characterization and its kinetics was developed by studying the macro-morphological characteristics of Mortierella alpina, an oleaginous zygomycete widely used to produce lipids rich in PUFA, in function of culture medium composition and to link morphological features of fungus with the level of lipid production. A number of distinct morphological forms including hollow pellets, fluffy pellets and freely dispersed mycelia were obtained by changing the fermentation factors. By fitting a Logistic curve, the maximum specific growth rate (μmax)was obtained, which determined the final mycelia morphology. μmax of 0.6584 in three kind of morphological forms is the more appropriate. According to the Luedeking-Piret equation fitting, α≠0 and β≠0, lipid production was partially associated with the hyphal growth, fluffy pellets which turn glucose into lipidwas more effective than the other two kinds of morphological forms.

Patients with primary biliary cholangitis (PBC) can have extrahepatic manifestations. However, data about cardiac involvement of PBC is limited. We aimed in this study to analyze the clinical characteristics in patients with PBC complicated with and without cardiac involvement, and the risk factors of cardiac involvement in PBC. PBC patients admitted to Peking Union Medical College Hospital between January 2002 and February 2016 were consecutively enrolled. Structured interview, systemic rheumatologic examination, and laboratory tests were conducted for each patient, and risk factors of cardiac involvement were analyzed by comparing patients with and without cardiac involvement. In total, 580 PBC patients were enrolled, and cardiac involvement was identified in 24 patients (4%), with 11 male (46%) and a mean age of 57±8 year. Cardiomyopathy and arrhythmias were presented in 17 (70.8%) and 21 (87.5%) patients, respectively. Patients with cardiac involvement were more frequently male (46% vs. 11%, P

Previous studies have found the association between rs10865331 in 2p15 area and ankylosing spondylitis (AS). This study aimed to identify additional functional genetic variants in 2p15 region associated with AS susceptibility.We used next generation sequencing (NGS) in 100 AS cases and 100 healthy controls to screen AS susceptible genetic variants, and validated these variants in 620 cases and 620 controls by using imLDRTM technique for single nucleotide polymorphism (SNP) genotyping.Totally, we identified 12 SNPs that might confer susceptibility to AS. Of those SNPs, three (rs14170, rs2123111 and rs1729674) were nominally associated (P

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor survival rates. The presence of cancer stem-like cells (CSCs) is believed to be among the underlying reasons for the aggressiveness of PDAC, which contributes to chemoresistance and recurrence. However, the mechanisms that induce chemoresistance and inhibit apoptosis remain largely unknown.We used serum-free medium to enrich CSCs from panc-1 human pancreatic cancer cells and performed sphere formation testing, flow cytometry, quantitative reverse transcription polymerase chain reaction (RT-qPCR) and semi-quantitative western blotting to confirm the stemness of panc-1 CSCs. Hallmarks of endoplasmic reticulum (ER) stress, including IRE1, PERK, ATF4, ATF6α, GRP78 and uPA expression, were detected after gemcitabine treatment. Effects of gemcitabine-induced uPA expression on cell invasion, sphere formation, colony formation and gemcitabine sensitivity were detected. Electrophoretic mobility shift assays (EMSAs) and RNA-immunoprecipitation (RIP) were performed to detect interaction between the uPA mRNA 3'-UTR and mutant p53-R273H expressed by panc-1 CSCs. The effects of upregulated uPA by gemcitabine on apoptosis were detected by Annexin V-FITC/PI staining, and the impact of uPA on small molecule CP-31398-restored mutant p53 transcriptional activity was measured by a luciferase reporter assay.Enriched panc-1 CSCs expressing high levels of CD44 and CD133 also produced significantly higher amounts of Oct4 and Nanog. Compared with panc-1 cells, panc-1 CSCs presented chemoresistance to gemcitabine. ER stress gene detections demonstrated effects of gemcitabine-induced ER stress on both the pro-apoptotic and pro-survival branches. ER stress-induced ATF6α upregulated level of uPA by transcriptionally activating GRP78. Gemcitabine-induced uPA promoted invasion, sphere formation and colony formation and attenuated apoptosis induced by gemcitabine in panc-1 CSCs, depending on interaction with mutant p53-R273H. Upregulation of uPA abolished CP-31398-mediated restoration of mutant p53 transcriptional activity in panc-1 CSCs.Gemcitabine treatment induced ER stress and promoted mutant p53-R273H stabilization via transcriptionally activated uPA which may contribute to chemoresistance to gemcitabine. Notably, upregulation of uPA by gemcitabine treatment may lead to the failure of CP-31398; thus, a novel strategy for modulating mutant p53 function needs to be developed.

Clinical guidelines recommend early discharge of patients with low-risk pulmonary embolism (LRPE). This study measured the overall impact of early discharge of LRPE patients on clinical outcomes and costs in the Veterans Health Administration population. Adult patients with ≥1 inpatient diagnosis for pulmonary embolism (PE) (index date) between 10/2011-06/2015, continuous enrollment for ≥12 months pre- and 3 months post-index date were included. PE risk stratification was performed using the simplified Pulmonary Embolism Stratification Index. Propensity score matching (PSM) was used to compare 90-day adverse PE events (APEs) [recurrent venous thromboembolism, major bleed and death], hospital-acquired complications (HACs), healthcare utilization, and costs among short (≤2 days) versus long length of stay (LOS). Net clinical benefit was defined as 1 minus the combined rate of APE and HAC. Among 6,746 PE patients, 95.4% were men, 22.0% were African American, and 1,918 had LRPE. Among LRPE patients, only 688 had a short LOS. After 1:1 PSM, there were no differences in APE, but short LOS had fewer HAC (1.5% vs 13.3%, 95% CI: 3.77-19.94) and bacterial pneumonias (5.9% vs 11.7%, 95% CI: 1.24-3.23), resulting in better net clinical benefit (86.9% vs 78.3%, 95% CI: 0.84-0.96). Among long LOS patients, HACs (52) exceeded APEs (14 recurrent DVT, 5 bleeds). Short LOS incurred lower inpatient ($2,164 vs $5,100, 95% CI: $646.8-$5225.0) and total costs ($9,056 vs $12,544, 95% CI: $636.6-$6337.7). LRPE patients with short LOS had better net clinical outcomes at lower costs than matched LRPE patients with long LOS.