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Abstract Decreased myocardial capillary density has been reported as an important histopathological feature associated with various heart disorders. Quantitative assessment of cardiac capillarization typically involves double immunostaining of cardiomyocytes (CMs) and capillaries in myocardial slices. In contrast, single immunostaining of basement membrane protein is a straightforward approach to simultaneously label CMs and capillaries, presenting fewer challenges in background staining. However, subsequent image analysis always requires expertise and laborious manual work to identify and segment CMs/capillaries. Here, we developed an image analysis tool, AutoQC, for automatic identification and segmentation of CMs and capillaries in immunofluorescence images of basement membrane. Commonly used capillarization-related measurements can be derived from segmentation results. By leveraging the power of a pre-trained segmentation model (Segment Anything Model, SAM) via prompt engineering, the training of AutoQC required only a small dataset with bounding box annotations instead of pixel-wise annotations. AutoQC outperformed SAM (without prompt engineering) and YOLOv8-Seg, a state-of-the-art instance segmentation model, in both instance segmentation and capillarization assessment. Thus, AutoQC, featuring a weakly supervised algorithm, enables automatic segmentation and high-throughput, high-accuracy capillarization assessment in basement-membrane-immunostained myocardial slices. This approach reduces the training workload and eliminates the need for manual image analysis once AutoQC is trained.

PurposeMedication overuse headache (MOH) is a chronic headache caused by regular overuse of medications. OnabotulinumtoxinA (BoNTA) is used for preventive treatment of MOH. However, its efficacy and safety remain controversial.MethodsSeven online databases (Cochrane Library, Embase, Medline, PubMed, China National Knowledge Infrastructure, Wanfang data, and Chinese BioMedical Literature Database) were searched for relevant articles published between January 2002 and March 2024. We included randomized controlled trials (RCTs) and cohort studies on the treatment of MOH using BoNTA versus a placebo or other active treatments.ResultsWe retrieved 487 articles in the database search. Of these, four eligible RCTs were identified after detailed screening. A total of 1,259 patients with MOH (622 patients treated with BoNTA, 607 with placebo, and 30 with topiramate) were included in the four RCTs. We found that BoNTA significantly reduced headache frequency compared with placebo (mean difference, 1.89; 95% confidence interval (CI), 1.11–2.67; I2 = 0%; p

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) ranks among the deadliest types of cancer, and it will be meaningful to search for new biomarkers with prognostic value to help clinicians tailor therapeutic strategies. Methods Here we tried to use an advanced optical imaging technique, multiphoton microscopy (MPM) combining second-harmonic generation (SHG) and two-photon excited fluorescence (TPEF) imaging, for the label-free detection of PDAC tissues from a cohort of 149 patients. An automated image processing method was used to extract collagen features from SHG images and the Kaplan-Meier survival analysis and Cox proportional hazards regression were used to assess the prognostic value of collagen signatures. Results SHG images clearly show the different characteristics of collagen fibers in tumor microenvironment. We gained eight collagen morphological features, and a Feature-score was derived for each patient by the combination of these features using ridge regression. Statistical analyses reveal that Feature-score is an independent factor, and can predict the overall survival of PDAC patients as well as provide well risk stratification. Conclusions SHG imaging technique can potentially be a tool for the accurate diagnosis of PDAC, and this optical biomarker (Feature-score) may help clinicians make more approximate treatment decisions.

Abstract Bovine viral diarrhea virus (BVDV) belongs to the genus Pestivirus within the family Flaviviridae. Mitophagy plays important roles in virus-host interactions. Here, we provide evidence that non-cytopathic (NCP) BVDV shifts the balance of mitochondrial dynamics toward fission and induces mitophagy to inhibit innate immune responses. Mechanistically, NCP BVDV triggers the translocation of dynamin-related protein (Drp1) to mitochondria and stimulates its phosphorylation at Ser616, leading to mitochondrial fission. In parallel, NCP BVDV-induced complete mitophagy via Parkin-dependent pathway contributes to eliminating damaged mitochondria to inhibit MAVS- and mtDNA-cGAS-mediated innate immunity responses, mtROS-mediated inflammatory responses and apoptosis initiation. Importantly, we demonstrate that the LIR motif of ERNS is essential for mitophagy induction. In conclusion, this study is the first to show that NCP BVDV-induced mitophagy plays a central role in promoting cell survival and inhibiting innate immune responses in vitro.

Iron overload occurs due to excessive iron intake compared to the body’s demand, leading to iron deposition and impairment of multiple organ functions. Our previous study demonstrated that chronic oral administration of ferric citrate (FC) caused colonic inflammatory injury. However, the precise mechanism underlying this inflammatory response remains unclear. The current study aims to investigate the mechanism by which iron overload induced by FC exposure leads to colonic inflammation. To accomplish this, mice were orally exposed to three different concentrations of FC (71 mg/kg/bw (L), 143 mg/kg/bw (M) and 286 mg/kg/bw (H)) for continuous 16 weeks, with the control group receiving ultrapure water (C). Exposure to FC caused disturbances in the excretory system, altered colonic flora alpha diversity, and enriched pathogenic bacteria, such as Mucispirillum, Helicobacter, Desulfovibrio, and Shigella. These changes led to structural disorders of the colonic flora and an inflammatory response phenotype characterized by inflammatory cells infiltration, atrophy of intestinal glands, and irregular thickening of the intestinal wall. Mechanistic studies revealed that FC-exposure activated the NF-κB signaling pathway by up-regulating TLR4, MyD88, and NF-κB mRNA levels and protein expression. This activation resulted in increased production of pro-inflammatory cytokines, further contributing to the colonic inflammation. Additionally, in vitro experiments in SW480 cells confirmed the activation of NF-κB signaling pathway by FC exposure, consistent with the in vivo findings. The significance of this study lies in its elucidation of the mechanism by which iron overload caused by FC exposure leads to colonic inflammation. By identifying the role of pathogenic bacteria and the NF-κB signaling pathway, this study could potentially offer a crucial theoretical foundation for the research on iron overload, as well as provide valuable insights for clinical iron supplementation.

Abstract Background Invasion of the corpus callosum by sparganosis is rare in children. After invading the corpus callosum, sparganosis has various migration modes, which can break through the ependyma and enter the ventricles, thus causing secondary migratory brain injury. Case presentation A girl aged 4 years and 7 months presented with left lower limb paralysis for more than 50 days. Blood examination showed that the proportion and absolute number of eosinophils in the peripheral blood were increased. Furthermore, enzyme-linked immunosorbent assay of serum and cerebrospinal fluid samples revealed positivity for IgG and IgM antibodies for sparganosis. Initial magnetic resonance imaging (MRI) revealed ring-like enhancements in the right frontoparietal cortex, subcortical white matter, and splenium of the corpus callosum. Within 2 months, a fourth follow-up MRI showed that the lesion had spread to the left parietal cortex, subcortical white matter, and deep white matter in the right occipital lobe and right ventricular choroid plexus, with left parietal leptomeningeal enhancement. Conclusion Migratory movement is one of the characteristics of cerebral sparganosis. When sparganosis invades the corpus callosum, clinicians should be aware that it may then break through the ependyma and enter the lateral ventricles, leading to secondary migratory brain injury. Short-term follow-up MRI is necessary to evaluate the migration mode of sparganosis and dynamically guide treatment strategies.

Fine-grain and weak-texture magnesium alloys are the long-term development targets of lightweight structural materials. In this study, a new composite asymmetric extrusion (CAE) is developed, which, coupling with an asymmetric die and an asymmetric billet, is proposed to improve the strength–ductility of the Mg-3.8Al-1.1Sn-0.4Ca alloy. The influence of the asymmetric billet on the microstructure and mechanical properties was investigated. The findings revealed that the asymmetric billet can induce greater plastic deformation, resulting in an increase in the cumulative strain and an improved nucleation rate. The CAE sheets exhibit fine grains (4.4 μm) and a weak tilted texture (7.57 mrd). Furthermore, the asymmetric billet results in the microstructure not forming a gradient microstructure under gradient strain along the transverse direction (TD) direction. The CAE sheets exhibited good mechanical properties, with a yield strength (YS) of 253 MPa, ultimate tensile strength (UTS) of 331 MPa, and elongation (EL) of 20%. This development shows promise in achieving high-efficiency, low-cost production of magnesium alloys.

IntroductionEarly neurological deterioration (END) is common in acute ischemic stroke and is directly associated with poor outcome after stroke. Our aim is to develop and validate a nomogram to predict the risk of END after mechanical thrombectomy (MT) in acute ischemic stroke patients with anterior circulation large-vessel occlusion.MethodsWe conducted a real-world, multi-center study in patients with stroke treated with mechanical thrombectomy. END was defined as a worsening by 2 or more NIHSS points within 72-hour after stroke onset compared to admission. Multivariable logistic regression was used to determine the independent predictors of END, and the discrimination of the scale was assessed using the C-index. Calibration curves were constructed to evaluate the calibration of the nomogram, and decision curves were used to describe the benefits of using the nomogram.ResultsA total of 1007 patients were included in our study. Multivariate logistic regression analysis found age, admission systolic blood pressure, initial NIHSS scores, history of hyperlipemia, and location of occlusion were independent predictors of END. We developed a nomogram that included these 6 factors, and it revealed a prognostic accuracy with a C-index of 0.678 in the derivation group and 0.650 in the validation group. The calibration curves showed that the nomogram provided a good fit to the data, and the decision curves demonstrated a large net benefit.DiscussionOur study established and validated a nomogram to stratify the risk of END before mechanical embolectomy and identify high-risk patients, who should be more cautious when making clinical decisions.

Driving safety analysis has recently experienced unprecedented improvements thanks to technological advances in precise positioning sensors, artificial intelligence (AI)-based safety features, autonomous driving systems, connected vehicles, high-throughput computing, and edge computing servers. Particularly, deep learning (DL) methods empowered volume video processing to extract safety-related features from massive videos captured by roadside units (RSU). Safety metrics are commonly used measures to investigate crashes and near-conflict events. However, these metrics provide limited insight into the overall network-level traffic management. On the other hand, some safety assessment efforts are devoted to processing crash reports and identifying spatial and temporal patterns of crashes that correlate with road geometry, traffic volume, and weather conditions. This approach relies merely on crash reports and ignores the rich information of traffic videos that can help identify the role of safety violations in crashes. To bridge these two perspectives, we define a new set of network-level safety metrics (NSM) to assess the overall safety profile of traffic flow by processing imagery taken by RSU cameras. Our analysis suggests that NSMs show significant statistical associations with crash rates. This approach is different than simply generalizing the results of individual crash analyses, since all vehicles contribute to calculating NSMs, not only the ones involved in crash incidents. This perspective considers the traffic flow as a complex dynamic system where actions of some nodes can propagate through the network and influence the crash risk for other nodes. The analysis is carried out using six video cameras in the state of Arizona along with a 5-year crash report obtained from the Arizona Department of Transportation (ADOT). The results confirm that NSMs modulate the baseline crash probability. Therefore, online monitoring of NSMs can be used by traffic management teams and AI-based traffic monitoring systems for risk analysis and traffic control.

Abstract This paper explores deep learning (DL) methods that are used or have the potential to be used for traffic video analysis, emphasising driving safety for both autonomous vehicles and human‐operated vehicles. A typical processing pipeline is presented, which can be used to understand and interpret traffic videos by extracting operational safety metrics and providing general hints and guidelines to improve traffic safety. This processing framework includes several steps, including video enhancement, video stabilisation, semantic and incident segmentation, object detection and classification, trajectory extraction, speed estimation, event analysis, modelling, and anomaly detection. The main goal is to guide traffic analysts to develop their own custom‐built processing frameworks by selecting the best choices for each step and offering new designs for the lacking modules by providing a comparative analysis of the most successful conventional and DL‐based algorithms proposed for each step. Existing open‐source tools and public datasets that can help train DL models are also reviewed. To be more specific, exemplary traffic problems are reviewed and required steps are mentioned for each problem. Besides, connections to the closely related research areas of drivers' cognition evaluation, crowd‐sourcing‐based monitoring systems, edge computing in roadside infrastructures, automated driving systems‐equipped vehicles are investigated, and the missing gaps are highlighted. Finally, commercial implementations of traffic monitoring systems, their future outlook, and open problems and remaining challenges for widespread use of such systems are reviewed.

The changes of structure and function of pork myofibrillar protein induced by oxidation and its ability to bind flavor substances under different ionic conditions were studied. 2-methyl-butanal, 3-methyl-butanal, hexanal, octanal and nonanal were selected as volatile compounds in the experiment. The ability of myofibrillar protein to bind volatile compounds was observed by headspace combined gas chromatography. The results confirmed that the secondary structure and function of oxidized myofibrillar protein changed. Oxidized myofibrillar protein could promote the release of 2-methyl-butanal and nonanal. Moreover, the effect of oxidized myofibrillar protein on 3-methyl-butanal, hexanal and octanal was dependent on AAPH concentration. The addition of Na+ promoted the release of hexanal, while the addition of Na+, K+, Ca2+ and Mg2+ promoted the absorption of 2-methyl-butanal, 3-methyl-butanal, octanal and nonal. Consequently, during the processing and storage of meat and meat products, oxidation of meat protein could change its structure and function, and then affect the ability of protein to combine flavor substances. In addition, sodium chloride is partially replaced by other salts in meat products, resulting in changes in the ionic environment of proteins, resulting in changes in the ability of proteins to combine flavor substances, thus changing the flavor of meat products.

Abstract This study investigated the relationship between residence altitude and serum folate levels in healthy Tibetans living on the Tibetan Plateau. Participants were selected from those who underwent physical examinations at our health center between November 2019 and February 2020. Demographic characteristics and medical histories were collected, and fasting blood was tested for serum folate and other hematological indicators. The relationship between altitude and serum folate levels was analyzed using a multivariable linear regression model. Serum folate levels were associated with altitude (β = − 0.44; 95% confidence interval [CI] − 0.71; − 0.16), hemoglobin (β = − 0.01; 95% CI − 0.03; − 0.00), red blood cells (β = − 0.72; 95% CI − 1.18; − 0.27), hematocrit (β = − 0.07; 95% CI − 0.12; − 0.02), high-density lipoprotein cholesterol (β = 2.67; 95% CI 1.35; 3.98), and sex (β = 0.68; 95% CI 0.12; 1.23). Multivariate linear regression analysis revealed that altitude was negatively associated with serum folate levels. After adjusting for confounding factors, serum folate levels decreased by 0.33 ng/mL per each 500-m increase in altitude (β = − 0.33; 95% CI − 0.6; − 0.05; P = 0.022). Altitude was negatively associated with serum folate levels in Tibetan adults. The relationship between altitude and folate levels should be further explored in populations of different races and disease states. Further large-scale prospective studies should illustrate the causality of this relationship.

Current forest monitoring technologies including satellite remote sensing, manned/piloted aircraft, and observation towers leave uncertainties about a wildfire’s extent, behavior, and conditions in the fire’s near environment, particularly during its early growth. Rapid mapping and real-time fire monitoring can inform in-time intervention or management solutions to maximize beneficial fire outcomes. Drone systems’ unique features of 3D mobility, low flight altitude, and fast and easy deployment make them a valuable tool for early detection and assessment of wildland fires, especially in remote forests that are not easily accessible by ground vehicles. In addition, the lack of abundant, well-annotated aerial datasets – in part due to unmanned aerial vehicles’ (UAVs’) flight restrictions during prescribed burns and wildfires – has limited research advances in reliable data-driven fire detection and modeling techniques. While existing wildland fire datasets often include either color or thermal fire images, here we present (1) a multi-modal UAV-collected dataset of dual-feed side-by-side videos including both RGB and thermal images of a prescribed fire in an open canopy pine forest in Northern Arizona and (2) a deep learning-based methodology for detecting fire and smoke pixels at accuracy much higher than the usual single-channel video feeds. The collected images are labeled to “fire” or “no-fire” frames by two human experts using side-by-side RGB and thermal images to determine the label. To provide context to the main dataset’s aerial imagery, the included supplementary dataset provides a georeferenced pre-burn point cloud, an RGB orthomosaic, weather information, a burn plan, and other burn information. By using and expanding on this guide dataset, research can develop new data-driven fire detection, fire segmentation, and fire modeling techniques.

Peste des petits ruminants virus (PPRV) is an important pathogen that seriously influences the productivity of small ruminants worldwide. PPRV is lymphotropic in nature and SLAM was identified as the primary receptor for PPRV and other Morbilliviruses. Many viruses have been demonstrated to engage extracellular vesicles (EVs) to facilitate their replication and pathogenesis. Here, we provide evidence that PPRV infection significantly induced the secretion levels of EVs from goat PBMC, and that PPRV-H protein carried in EVs can enhance SLAM receptor expression in the recipient cells via suppressing miR-218, a negative miRNA directly targeting SLAM gene. Importantly, EVs-mediated increased SLAM expression enhances PPRV infectivity as well as the expression of various cytokines related to SLAM signaling pathway in the recipient cells. Moreover, our data reveal that PPRV associate EVs rapidly entry into the recipient cells mainly through macropinocytosis pathway and cooperated with caveolin- and clathrin-mediated endocytosis. Taken together, our findings identify a new strategy by PPRV to enhance virus infection and escape innate immunity by engaging EVs pathway.

Abstract Background Extrahepatic portal vein obstruction (EHPVO) is the most important cause of hematemesis in children. Intrahepatic left portal vein and superior mesenteric vein anastomosis, also known as meso-Rex bypass (MRB), is becoming the gold standard treatment for EHPVO. We analyzed the value of preoperative computed tomography (CT) in determining whether MRB is feasible in children with EHPVO. Results We retrieved data on 76 children with EHPVO (50 male, 26 female; median age, 5.9 years) who underwent MRB (n = 68) or the Warren procedure (n = 8) from 2013 to 2019 and retrospectively analyzed their clinical and CT characteristics. The Rex recess was categorized into four subtypes (types 1–4) depending on its diameter in CT images. Of all 76 children, 7.9% had a history of umbilical catheterization and 1.3% had leukemia. Sixteen patients (20 lesions) had associated malformations. A total of 72.4% of Rex recesses could be measured by CT, and their mean diameter was 3.5 ± 1.8 mm (range 0.6–10.5 mm). A type 1, 2, 3, and 4 Rex recess was present in 9.2%, 53.9%, 11.8%, and 25.0% of patients, respectively. MRB could be performed in patients with types 1, 2, and 3, but those with type 4 required further evaluation. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of CT were 100%, 83.8%, 42.1%, 100%, and 85.5%, respectively. Conclusions Among the four types of Rex recesses on CT angiography, types 1–3 allow for the performance of MRB.

Therapeutic hypothermia (TH) is potentially an important therapy for central nervous system (CNS) trauma. However, its clinical application remains controversial, hampered by two major factors: (1) Many of the CNS injury sites, such as the optic nerve (ON), are deeply buried, preventing access for local TH. The alternative is to apply TH systemically, which significantly limits the applicable temperature range. (2) Even with possible access for ‘local refrigeration’, cold-induced cellular damage offsets the benefit of TH. Here we present a clinically translatable model of traumatic optic neuropathy (TON) by applying clinical trans-nasal endoscopic surgery to goats and non-human primates. This model faithfully recapitulates clinical features of TON such as the injury site (pre-chiasmatic ON), the spatiotemporal pattern of neural degeneration, and the accessibility of local treatments with large operating space. We also developed a computer program to simplify the endoscopic procedure and expand this model to other large animal species. Moreover, applying a cold-protective treatment, inspired by our previous hibernation research, enables us to deliver deep hypothermia (4 °C) locally to mitigate inflammation and metabolic stress (indicated by the transcriptomic changes after injury) without cold-induced cellular damage, and confers prominent neuroprotection both structurally and functionally. Intriguingly, neither treatment alone was effective, demonstrating that in situ deep hypothermia combined with cold protection constitutes a breakthrough for TH as a therapy for TON and other CNS traumas.

Digital in-line holography (DIH) is broadly used to reconstruct 3D shapes of microscopic objects from their 2D holograms. One of the technical challenges in the reconstruction stage is eliminating the twin image originating from the phase-conjugate wavefront. The twin image removal is typically formulated as a non-linear inverse problem since the scattering process involved in generating the hologram is irreversible. Conventional phase recovery methods rely on multiple holographic imaging at different distances from the object plane along with iterative algorithms. Recently, end-to-end deep learning (DL) methods are utilized to reconstruct the object wavefront (as a surrogate for the 3D structure of the object) directly from the single-shot in-line digital hologram. However, massive data pairs are required to train the utilize DL model for an acceptable reconstruction precision. In contrast to typical image processing problems, well-curated datasets for in-line digital holography do not exist. The trained models are also highly influenced by the objects' morphological properties, hence can vary from one application to another. Therefore, data collection can be prohibitively laborious and time-consuming, as a critical drawback of using DL methods for DH. In this article, we propose a novel DL method that takes advantages of the main characteristic of auto-encoders for blind single-shot hologram reconstruction solely based on the captured sample and without the need for a large dataset of samples with available ground truth to train the model. The simulation results demonstrate the superior performance of the proposed method compared to the state-of-the-art methods used for single-shot hologram reconstruction.

Because of its flexibility and universality, Monte Carlo integral has become the preferred algorithm of most realistic image synthesis. However, the quality of rendered images is often affected by the estimated variance, which is mainly reflected in image noise visually. To reduce the variance, Monte Carlo rendering systems often require extensive sampling, which also causes a lot of time spent trying to render noiseless images. For this problem, we propose a Monte Carlo noise reduction algorithm based on deep neural networks and apply it to the efficient rendering of an indoor scene. The algorithm can reduce noise in real time. In order to solve the gradient disappearance problem of deep convolutional neural network, the residual structure of the network is added to the original convolutional network. The proposed algorithm can achieve better noise reduction quality in the real-time guarantee.

Background. The purpose of this study is to evaluate the accuracy of prenatal MRI in diagnosing choledochal cysts (CDC), evaluate the sensitivity and specificity of MRI signs in the diagnosis of fetal CDC, and first compare the trend of size of CC between prenatal and postpartum. Methods. A total of 18 fetal who were diagnosed with CDCs through prenatal MRI were enrolled in the study. We summarized and analyzed the prenatal clinical data and prognosis information of prenatal and postpartum surgery, then compared the sensitivity, specificity, and diagnostic accuracy of various signs of MRI and postpartum MRCP diagnosis of CC. Finally, we tried to compare the earliest prenatal detection of common bile duct cysts with the size of surgery, and calculated the growth rate of common bile duct cysts for the first time. Results. All 18 patients were delivered in our institution. Among these patients, 14 were confirmed with CDCs after postpartum surgery, two patients had CDCs that disappeared, and two patients were confirmed with cystic biliary atresia (CBA) through the Kasai operation. Furthermore, 13 patients with CDCs and two patients with CBA underwent MRCP before the operation, and one patient with CDCs ruptured at birth and underwent ultrasound diagnosis. The sensitivity and diagnostic compliance of prenatal MRI signs for the location were higher when compared to postnatal MRCP (100% vs. 76.9% and 83.3% vs. 66.7%): the cyst was located at the porta hepatis, which was higher than the lowest edge of the liver, and parallel to the hepatoduodenal ligament. Conclusion. Prenatal MRI is higher than that of US for diagnosing CDCs, specifically in identifying the location of the cyst and confirming the origin of the cyst. The length, width, and size of the CDC become slightly bigger in our study.

Magnetic mesoporous carbon (MMC) and magnetic activated carbon (MAC) are good functionalized carbon materials to use when applying environmental techniques. In this work, a series of efficient magnetic composite adsorbents containing Fe3O4 and carbon were prepared successfully and used for the adsorption of Cr(VI) ions in petrochemical wastewater. The morphology and structure of these magnetic adsorbents were characterized with FTIR, TG, XRD, VSM, BET, and SEM technologies. The effect of different factors, such as pH, adsorption time, initial Cr(VI) ions’ concentration, Fe3O4 loading, and adsorption time, on the adsorption behavior were discussed. The results showed that the 8%Fe3O4@MMC adsorbent exhibited a high removal rate, reutilization, and large adsorption capacity. The corresponding adsorption capacity and removal rate could reach 132.80 mg·g−1 and 99.60% when the pH value, adsorption time, and initial Cr(VI) ions’ concentration were 2, 180 min, and 80 mg·L−1 at 298 K. Four kinds of adsorption isotherm models were used for fitting the experimental data by the 8%Fe3O4@MMC adsorbent at different temperatures in detail, and a kinetic model and thermodynamic analysis also were performed carefully. The reutilization performance was investigated, and the Fe3O4@MMC adsorbent exhibited greater advantage in the adsorption of Cr(VI) ions. These good performances can be attributed to a unique uniform pore structure, different crystalline phases of Fe3O4 particles, and adsorption potential rule. Hence, the 8%Fe3O4@MMC adsorbent can be used in industrial petrochemical wastewater treatment.

Pigs are deeply involved in human lives; hence, their viruses are associated with public health. Here, we established the most comprehensive virome of healthy piglets to date, which provides a viromic baseline of weaned pigs for disease prevention and control, highlighting that longitudinal viromic monitoring is needed to better understand the dynamics of the virome in pig development and disease occurrence.

The Hongyuan breed Yak (Bos grunniens) belongs to a member of t the subfamily Bovinae. We provide a complete mitogenome of B. grunniens and analyze its phylogenetic relationship with other related species. Its mitogenome is a circular molecule with 16,322 bp in size, including 13 protein coding genes, 22 tRNA genes, 2 rRNA genes, and a non-coding control region (D-loop, CR) that are conserved in most Bovidae mitogenomes. The total base composition of the B. grunniens mitogenome is 33.67% A, 27.29% T, 25.84% C, and 13.20% G. The gene composition, structure and the arrangement for B. grunniens are similar to those of most other Bovidae species. Phylogenetic analysis of mitochondrial genomes of 30 close species with Bayesian inference and maximum likelihood based on 13 protein-coding genes indicated that B. grunniens breed Hongyuan is more closely related to B. grunniens breed Qinghai Plateau than to B. grunniens breed Xuedong and B. grunniens breed Maiwa. The complete mitogenome of B. grunniens breed Hongyuan provides a potentially useful resource for further exploration of the taxonomic status and phylogenetic relationships of Bovinae and related species.

Abstract Background In September 2012, Beijing, the capital of China, selected five tertiary hospitals as pilots to remove the previously allowed 15% markup for drug sales. However, while most research demonstrated the significant decrease in drug sales, the core issue of high health expenditure was not well solved because of the unintended policy impact. This study aimed to empirically evaluate the short-term and long-term unintended impacts on controlling medical expenses of Beijing’s zero markup drug policy from 2012 to 2015. Methods This study extracted 2012–2015 individual-level data from the Beijing Urban Employee Basic Medical Insurance (UEBMI) database and performed a propensity score-matched analysis to evaluate the short-term and long-term impacts on controlling medical expenses. All inpatients in the 5 pilot reform hospitals were selected as the intervention group, while inpatients in other tertiary hospitals were selected as the control group. Results A total of 520,996 inpatients were extracted in this study. For patients in the pilot hospitals, the total expenditures per admission decreased from 17,140.3 yuan in 2012 to 15,430.1 yuan in 2013 and then increased to 16,789.8 yuan in 2015. Expenditure on drugs reduced from 5811.7 yuan in 2012 to 3903.4 yuan in 2015. However, a significant substitution effect of medical consumables was first observed in the third quarter of 2014, which undermined the impact of the policy. In the long-term, the intervention group and control group demonstrated the same trend. Conclusions After the zero markup drug policy, expenditure on drugs revealed a continuous decline. However, the decline in total expenditure was weakened by the substitution effect of medical consumables in the long term.

Abstract Metallic nanoplates have attracted widespread interests owing to their functional versatility, which relies heavily on their morphologies. In this study, the shape stability of several metallic nanoplates with body-centered-cubic (bcc) lattices is investigated by employing molecular dynamics simulations. It is found that the nanoplate with (110) surface planes is the most stable compared to the ones with (111) and (001) surfaces, and their shapes evolve with different patterns as the temperature increases. The formation of differently orientated facets is observed in the (001) nanoplates, which leads to the accumulation of shear stress and thus results in the subsequent formation of saddle shape. The associated shape evolution is quantitatively characterized. Further simulations suggest that the shape stability could be tuned by facet orientations, nanoplate sizes (including diameter and thickness), and components.

Direct methanol fuel cells are promising for clean, sustainable energy, but catalysts should be optimized. Here the authors construct ultrathin nanoframes with rich crystalline defects to increase electrocatalytic activity of gold for methanol oxidation, which is surprisingly promoted by carbon monoxide.

The use of tetra-alkylcarbamides as novel ligands: N,N-butyl-N’,N’-hexylurea (L1: ABHU), and N,N-butyl-N’,N’-pentylurea (L2: ABPU), for the solvent extraction and complexation behaviors of uranium(VI) was synthesized and investigated in this study. The effects of HNO3 and NO3− concentrations in the aqueous phase on the distribution ratio of U(VI) were examined. Under 5 mol/L HNO3 concentration, DU reached 5.02 and 4.94 respectively without third-phase formation. During the extraction, slope measurements and IR spectral analysis revealed that the U(VI) complexes are a form of UO2(NO3)2·2L for both ligands. In addition, thermodynamic studies showed that the uranium extraction reaction was a spontaneous exothermic reaction. The deep structural analysis of the complexes was realized with DFT calculation. The bond length, bond properties, and topology of the complexes were discussed in detail to analyze the extraction behavior. This study enriches the coordination chemistry of U(VI) by tetra-alkylcarbamides, which may offer new clues for the design and synthesis of novel ligands for the separation, enrichment, and recovery of uranium in the nuclear fuel cycle.

Phosphorus in the soil accessible to plants can easily be combined with calcium ion, the content of which is high in karst rocky desertification (KRD) regions, thereby resulting in a low utilization efficiency of phosphorus. The application of phosphate-solubilizing bacteria (PSB) from the KRD region would facilitate enhanced phosphate availability in the soil. In the present study, the strains belonging to Acinetobacter, Paraburkholderia, and Pseudomonas with efficient phosphate-solubilizing ability were isolated from fruit tree rhizosphere soils in KRD regions. Particularly, Acinetobacter sp. Ac-14 had a sustained and stable phosphate-solubilizing ability (439–448 mg/L, 48–120 h). Calcium carbonate decreased the phosphate-solubilizing ability in liquid medium; however, it did not affect the solubilization index in agar-solidified medium. When cocultivated with Arabidopsis thaliana seedling, Ac-14 increased the number of lateral roots, fresh weight, and chlorophyll content of the seedlings. Metabolomics analysis revealed that Ac-14 could produce 23 types of organic acids, majorly including gluconic acid and D-(-)-quinic acid. Expression of Ac-14 glucose dehydrogenase gene (gcd) conferred Pseudomonas sp. Ps-12 with a sustained and stable phosphate-solubilizing ability, suggesting that the production of gluconic acid is an important mechanism that confers phosphate solubilization in bacteria. Moreover, Ac-14 could also produce indole acetic acid and ammonia. Collectively, the isolated Ac-14 from KRD regions possess an efficient phosphate-solubilizing ability and plant growth-promoting effect which could be exploited for enhancing phosphorus availability in KRD regions. This study holds significance for the improvement of soil fertility and agricultural sustainable development in phosphorus-deficient KRD regions.

A reasonable ultrasonic vibration network can improve the casting quality of aluminum alloy. Ultrasonic vibration network based on a honeycomb structure has been designed, referred to as a new vibration network. The new vibration network can solve the problems of nonuniform distribution of power ultrasonic wave, small working area and low volume of ultrasonic vibration network, low efficiency of the frequency spectrum and power spectrum, and poor quality of aluminum alloy casting. The number of vibration nodes can be determined based on the number of layers of the vibration source nodes. The edge length of regular hexagonal honeycomb cells can be determined based on the size of the casting ingot. The output power and resonant frequency of the ultrasonic vibration network can be adjusted in real time according to the status of aluminum alloy melt. A seven-node new ultrasonic network and a four-node ultrasonic network with a traditional structure were selected and used in the experiment and simulation of a 500 mm diameter 2219 aluminum alloy ingot. In comparison with the traditional four-node ultrasonic network, the effective volume and area, frequency spectrum efficiency, and comprehensive coverage probability of the seven-node new ultrasonic vibration network increased by 34.06%, 23.12%, 17.25%, and 0.308, respectively. The difference between the desired value and average efficiency of the power spectrum was 0.292 W/cm2, and the average grain size of aluminum alloy decreased by 34.98 microns. These results indicate that the efficiency of ultrasonic-vibration-assisted casting system and the quality of aluminum alloy casting can be improved using the new ultrasonic vibration network.

Abstract Background Curcumin, as a pro-apoptotic agent, is extensively studied to inhibit tumor cell growth of various tumor types. Previous work has demonstrated that curcumin inhibits cancer cell growth by targeting multiple signaling transduction and cellular processes. However, the role of curcumin in regulating cellular bioenergetic processes remains largely unknown. Methods Western blotting and qRT-PCR were performed to analyze the protein and mRNA level of indicated molecules, respectively. RTCA, CCK-8 assay, nude mice xenograft assay, and in vivo bioluminescence imaging were used to visualize the effects of curcmin on gastric cancer cell growth in vitro and in vivo. Seahorse bioenergetics analyzer was used to investigate the alteration of oxygen consumption and aerobic glycolysis rate. Results Curcumin significantly inhibited gastric tumor cell growth, proliferation and colony formation. We further investigated the role of curcumin in regulating cellular redox homeostasis and demonstrated that curcumin initiated severe cellular apoptosis via disrupting mitochondrial homeostasis, thereby enhancing cellular oxidative stress in gastric cancer cells. Furthermore, curcumin dramatically decreased mtDNA content and DNA polymerase γ (POLG) which contributed to reduced mitochondrial oxygen consumption and aerobic glycolysis. We found that curcumin induced POLG depletion via ROS generation, and POLG knockdown also reduced oxidative phosphorylation (OXPHOS) activity and cellular glycolytic rate which was partially rescued by ROS scavenger NAC, indiating POLG plays an important role in the treatment of gastric cancer. Data in the nude mice model verified that curcumin treatment significantly attenuated tumor growth in vivo. Finally, POLG was up-regulated in human gastric cancer tissues and primary gastric cancer cell growth was notably suppressed due to POLG deficiency. Conclusions Together, our data suggest a novel mechanism by which curcumin inhibited gastric tumor growth through excessive ROS generation, resulting in depletion of POLG and mtDNA, and the subsequent disruption of cellular bioenergetics.

ABSTRACT We previously revealed the involvement of extracellular regulated protein kinases 1/2 (ERK1/2) in interleukin-6 (IL-6) secretion induced by cyclic compressive force (CCF) in MLO-Y4 cells. In this study, we investigated the contributions of the p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways to IL-6 secretion by stimulating MLO-Y4 cells with CCF. At 80% confluence, different magnitudes (1000μstrain, 2000 μstrain and 4000 μstrain), frequencies (0.5 Hz, 1.0 Hz and 2.0 Hz) and durations (10 min, 30 min, 1 h, 3 h and 6 h) of CCF were loaded onto cells using a four-point bending system. Flow Cytometry (FCM) analysis was used to analyze cell mortality rates after CCF loading. p38 and p65 phosphorylation as well as IκBα degradation in MLO-Y4 cells were detected by Western blotting (WB). Changes in IL-6 secretion after inhibitor treatment were assessed by enzyme-linked immunosorbent assays (ELISAs). Cellular viability was over 90 percent after CCF. p38 and p65 phosphorylation increased under all conditions, whereas IκBα protein levels decreased. However, phosphorylation and degradation were not completely dependent on the loading magnitude, frequency or duration. Furthermore, p38 inhibition using the specific inhibitor SB203580 reduced both p38 phosphorylation and IL-6 secretion. Similarly, NF-κB inhibition using BAY 11-7082 decreased p65 phosphorylation and IL-6 secretion but increased the concentration of IκBα. These findings reveal significant roles for the p38 and NF-κB signaling pathways in IL-6 secretion induced by CCF in MLO-Y4 cells.

We previously screened the novel gene Ds-26-16 from a 4 M salt-stressed Dunaliella salina cDNA library and discovered that this gene conferred salt tolerance to broad-spectrum organisms, including E. coli (Escherichia coli), Haematococcus pluvialis and tobacco. To determine the mechanism of this gene conferring salt tolerance, we studied the proteome of E. coli overexpressing the full-length cDNA of Ds-26-16 using the iTRAQ (isobaric tags for relative and absolute quantification) approach. A total of 1,610 proteins were identified, which comprised 39.4% of the whole proteome. Of the 559 differential proteins, 259 were up-regulated and 300 were down-regulated. GO (gene ontology) and KEGG (Kyoto encyclopedia of genes and genomes) enrichment analyses identified 202 major proteins, including those involved in amino acid and organic acid metabolism, energy metabolism, carbon metabolism, ROS (reactive oxygen species) scavenging, membrane proteins and ABC (ATP binding cassette) transporters, and peptidoglycan synthesis, as well as 5 up-regulated transcription factors. Our iTRAQ data suggest that Ds-26-16 up-regulates the transcription factors in E. coli to enhance salt resistance through osmotic balance, energy metabolism, and oxidative stress protection. Changes in the proteome were also observed in E. coli overexpressing the ORF (open reading frame) of Ds-26-16. Furthermore, pH, nitric oxide and glycerol content analyses indicated that Ds-26-16 overexpression increases nitric oxide content but has no effect on glycerol content, thus confirming that enhanced nitric oxide synthesis via lower intercellular pH was one of the mechanisms by which Ds-26-16 confers salt tolerance to E. coli.

Currently, the purity of hybrid seed is a crucial limiting factor when developing hybrid japonica rice (Oryza sativa L.). To chemically control hybrid seed purity, we transferred an improved atrazine chlorohydrolase gene (atzA) from Pseudomonas ADP into hybrid japonica parental lines (two maintainers, one restorer), and Nipponbare, by using Agrobacterium-mediated transformation. We subsequently selected several transgenic lines from each genotype by using PCR, RT-PCR, and germination analysis. In the presence of the investigated atrazine concentrations, particularly 150 µM atrazine, almost all of the transgenic lines produced significantly larger seedlings, with similar or higher germination percentages, than did the respective controls. Although the seedlings of transgenic lines were taller and gained more root biomass compared to the respective control plants, their growth was nevertheless inhibited by atrazine treatment compared to that without treatment. When grown in soil containing 2 mg/kg or 5 mg/kg atrazine, the transgenic lines were taller, and had higher total chlorophyll contents than did the respective controls; moreover, three of the strongest transgenic lines completely recovered after 45 days of growth. After treatment with 2 mg/kg or 5 mg/kg of atrazine, the atrazine residue remaining in the soil was 2.9-7.0% or 0.8-8.7% respectively, for transgenic lines, and 44.0-59.2% or 28.1-30.8%, respectively, for control plants. Spraying plants at the vegetative growth stage with 0.15% atrazine effectively killed control plants, but not transgenic lines. Our results indicate that transgenic atzA rice plants show tolerance to atrazine, and may be used as parental lines in future hybrid seed production.

The innate immune system is the first line of host defense against infection and involves several different cell types. Here we investigated the role of the phosphatidylinositol 3 kinase (PI3K) signaling pathway in innate immune cells. By blocking this pathway with pharmacological inhibitors, we found that the production of proinflammatory cytokines was drastically suppressed in monocytes and macrophages. Further study revealed that the suppression was mainly related to the mammalian target of rapamycin (mTOR)/p70(S6K) signaling. In addition, we found that the PI3K pathway was involved in macrophage motility and neovascularization. Our data provide a rationale that inhibition of the PI3K signaling pathway could be an attractive approach for the management of inflammatory disorders.

Identification and evolution of salt tolerant genes are crucial steps in developing salt tolerant crops or microorganisms using biotechnology. Ds-26-16, a salt tolerant gene that was isolated from Dunaliella salina, encodes a transcription factor that can confer salt tolerance to a number of organisms including Escherichia coli (E. coli), Haematococcus pluvialis and tobacco. To further improve its salt tolerance, a random mutagenesis library was constructed using deoxyinosine triphosphate-mediated error-prone PCR technology, and then screened using an E. coli expression system that is based on its broad-spectrum salt tolerance. Seven variants with enhanced salt tolerance were obtained. Variant EP-5 that contained mutation S32P showed the most improvement with the E. coli transformant enduring salt concentrations up to 1.54 M, in comparison with 1.03 M for the wild type gene. Besides, Ds-26-16 and EP-5 also conferred E. coli transformant tolerance to freezing, cold, heat, Cu2+ and alkaline. Homology modeling revealed that mutation S32P in EP-5 caused the conformational change of N- and C-terminal α-helixes. Expression of Ds-26-16 and EP-5 maintained normal cellular morphology, increased the intracellular antioxidant enzymatic activity, reduced malondialdehyde content, and stimulated Nitric Oxide synthesis, thus enhancing salt tolerance to E. coli transformants.

BACKGROUND: Blood vessels in tumors express higher level of aminopeptidase N (APN) than normal tissues. Evidence suggests that the CNGRC motif is an APN ligand which targets tumor vasculature. Increased expression of APN in tumor vascular endothelium, therefore, offers an opportunity for targeted delivery of NGR peptide-linked drugs to tumors. METHODS/PRINCIPAL FINDINGS: To determine whether an additional cyclic CNGRC sequence could improve endothelial cell homing and antitumor effect, human plasminogen kringle 5 (hPK5) was modified genetically to introduce a CNGRC motif (NGR-hPK5) and was subsequently expressed in yeast. The biological activity of NGR-hPK5 was assessed and compared with that of wild-type hPK5, in vitro and in vivo. NGR-hPK5 showed more potent antiangiogenic activity than wild-type hPK5: the former had a stronger inhibitory effect on proliferation, migration and cord formation of vascular endothelial cells, and produced a stronger antiangiogenic response in the CAM assay. To evaluate the tumor-targeting ability, both wild-type hPK5 and NGR-hPK5 were (99 m)Tc-labeled, for tracking biodistribution in the in vivo tumor model. By planar imaging and biodistribution analyses of major organs, NGR-hPK5 was found localized to tumor tissues at a higher level than wild-type hPK5 (approximately 3-fold). Finally, the effects of wild-type hPK5 and NGR-modified hPK5 on tumor growth were investigated in two tumor model systems. NGR modification improved tumor localization and, as a consequence, effectively inhibited the growth of mouse Lewis lung carcinoma (LLC) and human colorectal adenocarcinoma (Colo 205) cells in tumor-bearing mice. CONCLUSIONS/SIGNIFICANCE: These studies indicated that the addition of an APN targeting peptide NGR sequence could improve the ability of hPK5 to inhibit angiogenesis and tumor growth.