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Abstract Aloperine (ALO), a quinolizidine‐type alkaloid isolated from a natural Chinese herb, has shown promising antitumor effects. Nevertheless, its common mechanism of action and specific target remain elusive. Here, it is demonstrated that ALO inhibits the proliferation and migration of non‐small cell lung cancer cell lines in vitro and the tumor development in several mouse tumor models in vivo. Mechanistically, ALO inhibits the fusion of autophagosomes with lysosomes and the autophagic flux, leading to the accumulation of sequestosome‐1 (SQSTM1) and production of reactive oxygen species (ROS), thereby inducing tumor cell apoptosis and preventing tumor growth. Knockdown of SQSTM1 in cells inhibits ROS production and reverses ALO‐induced cell apoptosis. Furthermore, VPS4A is identified as a direct target of ALO, and the amino acids F153 and D263 of VPS4A are confirmed as the binding sites for ALO. Knockout of VPS4A in H1299 cells demonstrates a similar biological effect as ALO treatment. Additionally, ALO enhances the efficacy of the anti‐PD‐L1/TGF‐β bispecific antibody in inhibiting LLC‐derived subcutaneous tumor models. Thus, ALO is first identified as a novel late‐stage autophagy inhibitor that triggers tumor cell death by targeting VPS4A.

This research aimed to study the impact of different altitudes on the flue gas temperature and thermal stratification in the highway tunnel with a vertical shaft, by establishing a full-sized tunnel model using the numerical simulation software Fire Dynamics Simulator (FDS). Simulation experimental results were analyzed and it was found: first, with the same heat release power of fire source, the vertical, transverse and roof temperatures of both fire source and non-fire source sections in the tunnel all increased to a certain extent along with the increase of altitude; second, the vertical, transverse and roof temperatures of the tunnel all increased with the increased heat release rate of fire source at the same altitude, and the temperature of the fire source section was higher than that of the non-fire source section as a whole; third, the average temperature and stratification intensity of vertical flue gas in both sections showed an increasing trend with the increase of altitude, indicating that the intensity of flue gas thermal stratification at high altitude was greater than that at low altitude, because a large amount of flue gas accumulated in the upper tunnel and led to the increase of the roof flue gas temperature at high altitude.

Summary: Apolipoprotein E (apoE) plays a crucial role in the pathogenesis of Alzheimer’s disease (AD). Microglia exhibit a substantial upregulation of apoE in AD-associated circumstances, despite astrocytes being the primary source of apoE expression and secretion in the brain. Although the role of astrocytic apoE in the brain has been extensively investigated, it remains unclear that whether and how apoE particles generated from astrocytes and microglia differ in biological characteristic and function. Here, we demonstrate the differences in size between apoE particles generated from microglia and astrocytes. Microglial apoE particles impair neurite growth and synapses, and promote neuronal senescence, whereas depletion of GPNMB (glycoprotein non-metastatic melanoma protein B) in microglial apoE particles mitigated these deleterious effects. In addition, human APOE4-expressing microglia are more neurotoxic than APOE3-bearing microglia. For the first time, these results offer concrete evidence that apoE particles produced by microglia are involved in neuronal senescence and toxicity.

Although many studies have considered the effects of online reviews on tourists’ decisions, none have directly investigated how to leverage open data analyses to create early choice sets and facilitate destination planning. This paper illustrates how salient characteristics can be mined from the shared experiences embedded in review data and incorporated into a predictive model to build a travel counseling approach. The model is designed by first defining a prediction-based mechanism from online reviews and then generating a multinomial classification problem on all candidate destinations of interest. The model is implemented by applying Natural Language Processing (NLP) and Deep Learning (DL) technologies to review textual features. The model is validated using 75,315 reviews from TripAdvisor along with destinations from 257 U.S. national parks. Empirical results indicate a best classification accuracy of 67%, outperforming two previous approaches. Findings shed light on how to exploit past tourists’ experiences to generate early destination recommendations to identify items for choice sets and reduce tourists’ travel-planning effort. Theoretical and managerial implications regarding social media analytics are provided based on online review meta-data in touristic management.

Abstract Recent text generation methods frequently learn node representations from graph‐based data via global or local aggregation, such as knowledge graphs. Since all nodes are connected directly, node global representation encoding enables direct communication between two distant nodes while disregarding graph topology. Node local representation encoding, which captures the graph structure, considers the connections between nearby nodes but misses out onlong‐range relations. A quantum‐like approach to learning better‐contextualised node embeddings is proposed using a fusion model that combines both encoding strategies. Our methods significantly improve on two graph‐to‐text datasets compared to state‐of‐the‐art models in various experiments.

Abstract Background Most displaced femoral neck fractures can achieve satisfactory anatomical reduction by closed reduction, but there are still some that cannot reset satisfactorily after closed reduction, and open reduction are required. Such fractures that cannot be repositioned successfully by closed reduction are called irreducible displaced femoral neck fractures in this study. The objective of our study was to evaluate the efficacy of direct anterior incision with the Femoral Neck System in the treatment of irreducible displaced femoral fractures. Methods A total of 16 young and middle-aged patients with irreducible displaced femoral neck fractures involving Garden type III and IV were treated using Femoral Neck System fixation by open reduction through Direct Anterior Approach between January 2020 to September 2021. Functional outcomes and postoperative complications were assessed during follow-up. Clinical outcomes were evaluated by the Hip Harris score. The postoperative reduction was evaluated by the Garden Index. Observe postoperative complications. Results All patients were followed up with a mean follow-up time of 21.1(12–30) months, and according to radiological results, all patients achieved fracture healing, with a mean healing time of 4.25 months. All 16 patients received grade Garden I and II reductions, and there was no significant difference in the anteroposterior Garden reduction index between the first day after surgery (166.13 ± 5.61) and the 12th month after surgery(164.94 ± 4.49) (P>0.05) and no significant difference in lateral Garden index between the first day after surgery(171.06 ± 4.46) and the 12th month after surgery(169.38 ± 3.98) (P

The paper presents a vision-based obstacle avoidance strategy for lightweight self-driving cars that can be run on a CPU-only device using a single RGB-D camera. The method consists of two steps: visual perception and path planning. The visual perception part uses ORBSLAM3 enhanced with optical flow to estimate the car’s poses and extract rich texture information from the scene. In the path planning phase, the proposed method employs a method combining a control Lyapunov function and control barrier function in the form of a quadratic program (CLF-CBF-QP) together with an obstacle shape reconstruction process (SRP) to plan safe and stable trajectories. To validate the performance and robustness of the proposed method, simulation experiments were conducted with a car in various complex indoor environments using the Gazebo simulation environment. The proposed method can effectively avoid obstacles in the scenes. The proposed algorithm outperforms benchmark algorithms in achieving more stable and shorter trajectories across multiple simulated scenes.

Reducing fruit and vegetable waste and maintaining quality has become challenging for everyone. Nanotechnology is a new and intriguing technology that is currently being implemented in fruit and vegetable preservation. Silver nanomaterials provide superior antibacterial qualities, biodegradability, and biocompatibility, which expands their potential applications in fruit and vegetable preservation. Silver nanomaterials include silver nanocomposites and Ag-MOF, of which silver nanocomposites are mainly composed of silver nanoparticles. Notably, not all kinds of silver nanoparticles utilized in the preservation of fruits and vegetables are thoroughly described. Therefore, the synthesis, mechanism of action, and advancements in research on silver nanocomposites for fruit and vegetable preservation were discussed in this study.

Introduction: Wound healing is a delicate and complex process influenced by many factors. The treatment of skin wounds commonly involves the use of wound dressings, which remain a routine approach. An ideal dressing can provide protection and a suitable environment for wound surfaces by maintaining moisture and exhibiting good biocompatibility, mechanical strength, and antibacterial properties to promote healing and prevent infection.Methods: We encapsulated tick-derived antibacterial polypeptides (Os) as a model drug within a methylacrylyl gelatin (GelMA) hydrogel containing MXene nanoparticles. The prepared composite hydrogels were evaluated for their wound dressing potential by analyzing surface morphology, mechanical properties, swelling behavior, degradation properties, antibacterial activity, and cytocompatibility.Results: The results demonstrated excellent mechanical strength, swelling performance, degradation behavior, and antibacterial activity of the prepared composite hydrogels, effectively promoting cell growth, adhesion, and expression of antibacterial peptide activity. A full-thickness rat wound model then observed the wound healing process and surface interactions between the composite hydrogels and wounds. The composite hydrogel significantly accelerated wound closure, reduced inflammation, and sped epithelial formation and maturation.Discussion: Incorporating antibacterial peptides into GelMA provides a feasible strategy for developing excellent antibacterial wound dressings capable of tissue repair. In conclusion, this study presents a GelMA-based approach for designing antibacterial dressings with strong tissue regenerative ability.

Abstract Background Inflammasome activation has a pathogenic role in Parkinson’s disease (PD). Up-regulated expressions of inflammasome adaptor apoptosis-associated speck-like protein containing a CARD (ASC) and assembly of ASC specks have been observed in postmortems of human PD brains and experimental PD models. Extracellular ASC specks behave like danger signals and sustain prolonged inflammasome activation. However, the contribution of ASC specks in propagation of inflammasome activation and pathological progression in PD has not been fully established. Methods Herein, we used human A53T mutant α-synuclein preformed fibrils (PFFs)-stimulated microglia in vitro and unilateral striatal stereotaxic injection of PFFs-induced mice model of PD in vivo, to investigate the significance of ASC specks in PD pathological progression. Rotarod and open-field tests were performed to measure motor behaviors of indicated mice. Changes in the molecular expression were evaluated by immunofluorescence and immunoblotting (IB). Intracellular knockdown of the ASC in BV2 cells was performed using si-RNA. Microglial and neuronal cells were co-cultured in a trans-well system to determine the effects of ASC knockdown on cytoprotection. Results We observed a direct relationship between levels of ASC protein and misfolded α‑synuclein aggregates in PD mice brains. ASC specks amplified NLRP3 inflammasome activation driven by α-synuclein PFFs stimulation, which aggravated reactive microgliosis and accelerated α‑synuclein pathology, dopaminergic neurodegeneration and motor deficits. Endogenous ASC knockdown suppressed microglial inflammasome activation and neuronal α‑synuclein aggregation. Conclusions In conclusion, our study elucidated that ASC specks contribute to the propagation of inflammasome activation-associated α‑synuclein pathology in PD, which forms the basis for targeting ASC as a potential therapy for PD.

This paper aims to study the effects of altitude and the size of smoke outlet on fire smoke diffusion and discharge in semi-lateral smoke exhaust highway tunnels. At first, simulations of semi-lateral smoke exhaust highway tunnels were carried out in FDS (Fire Dynamics Simulator), then the distribution laws of temperature, CO concentration, smoke mass flow, and visibility in the tunnel under the conditions of different altitudes and smoke outlet areas were analyzed to figure out the effects of altitude and size of smoke outlet on fire smoke diffusion and discharge in the said tunnels. The results suggest that, in case of the same fire source power, the velocity of smoke diffusion increases with the altitude; for curves of different altitudes, the tunnel roof temperature features are basically the same, that is, the higher the altitude, the higher the temperature at the tunnel roof. When the fire source power is 20 MW, the smoke mass flow at the smoke outlet decreases with the increase of altitude, but the CO concentration grows with it, indicating that the smoke exhaust efficiency is higher in high-altitude areas. When the altitude reaches 4200 m and the fire source power is 20 MW, with the increase of smoke outlet area, the smoke discharge effect of the tunnel shows an upward trend, taking both the smoke discharge effect and economy into consideration; the smoke outlet should take a size of 4 x 3 m.

Abstract Apolipoprotein E (APOE) plays a pivotal role in lipid including cholesterol metabolism. The APOE ε4 (APOE4) allele is a major genetic risk factor for Alzheimer’s and cardiovascular diseases. Although APOE has recently been associated with increased susceptibility to infections of several viruses, whether and how APOE and its isoforms affect SARS-CoV-2 infection remains unclear. Here, we show that serum concentrations of APOE correlate inversely with levels of cytokine/chemokine in 73 COVID-19 patients. Utilizing multiple protein interaction assays, we demonstrate that APOE3 and APOE4 interact with the SARS-CoV-2 receptor ACE2; and APOE/ACE2 interactions require zinc metallopeptidase domain of ACE2, a key docking site for SARS-CoV-2 Spike protein. In addition, immuno-imaging assays using confocal, super-resolution, and transmission electron microscopies reveal that both APOE3 and APOE4 reduce ACE2/Spike-mediated viral entry into cells. Interestingly, while having a comparable binding affinity to ACE2, APOE4 inhibits viral entry to a lesser extent compared to APOE3, which is likely due to APOE4’s more compact structure and smaller spatial obstacle to compete against Spike binding to ACE2. Furthermore, APOE ε4 carriers clinically correlate with increased SARS-CoV-2 infection and elevated serum inflammatory factors in 142 COVID-19 patients assessed. Our study suggests a regulatory mechanism underlying SARS-CoV-2 infection through APOE interactions with ACE2, which may explain in part increased COVID-19 infection and disease severity in APOE ε4 carriers.

Improving phosphorus (P) acquisition efficiency is important for sustainable agriculture. Here, the authors report a natural variation in an upstream open reading frame of a SEC12-like gene GmPHF1 is crucial for protein abundance and spatial distribution of GmPHF1, which contribute to P acquisition diversity in soybean.

Introduction: Diffuse alveolar hemorrhage (DAH) is a serious complication caused by systemic lupus erythematosus (SLE). Tissue damage and changes in immune response are all associated with excessive free radical production. Therefore, removing excess reactive oxygen species are considered a feasible scheme for diffuse alveolar hemorrhage treatment. Cyclophosphamide is often used as the main therapeutic drug in clinics. However, CTX carries a high risk of dose-increasing toxicity, treatment intolerance, and high recurrence rate. The combination of therapeutic drugs and functional nanocarriers may provide an effective solution. PDA is rich in phenolic groups, which can remove the reactive oxygen species generated in inflammatory reactions, and can serve as excellent free radical scavengers.Methods: We developed a hollow polydopamine (HPDA) nanocarrier loaded with CTX by ionization to prepare the novel nanoplatform, CTX@HPDA, for DAH treatment. The monodisperse silica nanoparticles were acquired by reference to the typical Stober method. PDA was coated on the surface of SiO2 by oxidation self-polymerization method to obtain SiO2@PDA NPs. Then, HPDA NPs were obtained by HF etching. Then HPDA was loaded with CTX by ionization to prepare CTX@HPDA. Then we tested the photothermal effect, animal model therapeutics effect, and biosafety of CTX@HPDA.Results: Material tests showed that the CTX@ HPDA nanoplatform had a uniform diameter and could release CTX in acidic environments. The vitro experiments demonstrated that CTX@HPDA has good photothermal conversion ability and photothermal stability. Animal experiments demonstrated that the CTX@HPDA nanoplatform had good biocompatibility. The nanoplatform can dissociate in acidic SLE environment and trigger CTX release through photothermal conversion. Combining HPDA, which scavenges oxygen free radicals, and CTX, which has immunosuppressive effect, can treat pulmonary hemorrhage in SLE. Micro-CT can be used to continuously analyze DAH severity and lung changes in mice after treatment. The pulmonary exudation in the various treatment groups improved to varying degrees.Discussion: In this study, we report a photothermal/PH-triggered nanocarrier (CTX@HPDA) for the precise treatment of SLE-DAH. CTX@HPDA is a simple and efficient nanocarrier system for DAH therapy. This work provides valuable insights into SLE treatment.

IntroductionThe anti-tumor vindoline and catharanthine alkaloids are naturally existed in Catharanthus roseus (C. roseus), an ornamental plant in many tropical countries. Plant-specific TEOSINTE BRANCHED1/CYCLOIDEA/PCF (TCP) transcription factors play important roles in various plant developmental processes. However, the roles of C. roseus TCPs (CrTCPs) in terpenoid indole alkaloid (TIA) biosynthesis are largely unknown.MethodsHere, a total of 15 CrTCP genes were identified in the newly updated C. roseus genome and were grouped into three major classes (P-type, C-type and CYC/TB1).ResultsGene structure and protein motif analyses showed that CrTCPs have diverse intron-exon patterns and protein motif distributions. A number of stress responsive cis-elements were identified in promoter regions of CrTCPs. Expression analysis showed that three CrTCP genes (CrTCP2, CrTCP4, and CrTCP7) were expressed specifically in leaves and four CrTCP genes (CrTCP13, CrTCP8, CrTCP6, and CrTCP10) were expressed specifically in flowers. HPLC analysis showed that the contents of three classic TIAs, vindoline, catharanthine and ajmalicine, were significantly increased by ultraviolet-B (UV-B) and methyl jasmonate (MeJA) in leaves. By analyzing the expression patterns under UV-B radiation and MeJA application with qRT-PCR, a number of CrTCP and TIA biosynthesis-related genes were identified to be responsive to UV-B and MeJA treatments. Interestingly, two TCP binding elements (GGNCCCAC and GTGGNCCC) were identified in several TIA biosynthesis-related genes, suggesting that they were potential target genes of CrTCPs. DiscussionThese results suggest that CrTCPs are involved in the regulation of the biosynthesis of TIAs, and provide a basis for further functional identification of CrTCPs.

This paper discusses four kinds of hole sealing technologies for gas drainage in soft coal seam, which are polyurethane hole sealing, cement mortar hole sealing, full-length screen pipe hole sealing and pipe direct connection technology. Through the observation of negative pressure loss, the sealing effect of four sealing technologies is analyzed, the polyurethane sealing effect is poor, the cement mortar, the full-length screen pipe combined with cement mortar and the direct connection technology of pipe are good; through the observation of gas concentration, the gas drainage effect of four sealing technologies is analyzed, the polyurethane sealing technology is the worst, and the direct connection technology of pipe is the worst. The gas drainage effect is the best; according to the sealing effect and gas drainage effect, the traditional polyurethane and cement mortar sealing technology cannot meet the gas drainage demand of the soft coal seam. In the case of slow drilling deformation, the full-length screen pipe sealing technology can be used. In the case of rapid drilling deformation, the direct connection of pipe sealing technology should be used.

Based on the diversity and importance of phycospheric microorganisms as well as their complex interaction with algae, their ecological correlation with algal bloom events has become a research topic of great interest that remains unclear in the natural dynamic process of harmful macroalgal blooms (HMBs). The world’s largest green tides caused by macroalgae Ulva prolifera have occurred in the Yellow Sea for 16 consecutive years, and seriously affected the coastal ecosystem. Here, we monitored the spatiotemporal dynamics of the phycospheric bacterial community during the U. prolifera green tide bloom. The 73-day continuous field survey covered the whole process of initial invasion until the extinction of the green tide. The phycospheric bacterial community has a higher richness than the control seawater bacteria; in addition, it has more enriched taxa with organic nutrition preference and environmental pressure adaption, such as Bacteroidetes, Firmicutes, and Desulfobacterota. The same differences in populations and functional profiles were observed among the epiphytic bacterial and phycospheric seawater bacterial communities, which may be driven by the spatial heterogeneity of biogenic elements (e.g., organic nutrients and oxygen) among the habitats. Significant succession occurred in both the epiphytic bacterial and phycospheric seawater bacterial communities; their diversity and richness exhibited significant heterogeneity variation patterns, and their community structure became more similar in late phases. Our study revealed that macroalgal phycospheric microbial communities have a highly complex and dynamic composition and variable ecological functions, which indicate that phycospheric microorganisms are closely related to the fate of HMBs and may have the profound effect coastal biogeochemical cycles.

Abstract Ulva prolifera green tides, one of the greatest marine ecological disasters, originate in the southern Yellow Sea of China and obtain the highest biomass in Haizhou Bay (latitude around 35° N) during northward drift. U. prolifera shows different morphologies from southern Haizhou Bay (SH) to northern Haizhou Bay (NH). Owing to the distinct nutrient environments between SH and NH, we hypothesized that thalli in NH with poor nutrients increased the surface area to volume ratio (SA:VOL) to better absorb nutrients. Here, we tested this hypothesis by comparing the SA:VOL of thalli in SH and NH. The results showed that the thalli in NH had a lower SA:VOL than those in SH, and SA:VOL had positive relationships with temperature and nutrients, contrary to the general hypothesis. The novel results suggested that morphological differences of U. prolifera were the result of developmental state rather than environmental acclimation. Indicators of reproduction (reproductive allocation ratio) were negatively related to variation in tissue contents of C, N, P, and crude protein, whereas indicators of growth (tissue contents of C, N, P, and crude protein) showed significant positive influences on SA:VOL. The results indicated that a trade‐off relationship between reproduction and growth existed in the northward drift. All the results suggested that physiological functional traits affected morphological variation of U. prolifera in different environmental conditions during the drifting of green tides. This study presents new insights into the opportunist species nature of U. prolifera through morphological variation and associated functional consequences.

Waterborne Benzo[a]pyrene (B[a]P) pollution is a global threat to aquatic organisms. The exposure to waterborne B[a]P can disrupt the normal locomotor behavior of zebrafish (Danio rerio), however, how it affect the locomotor behavior of adult zebrafish remains unclear. Herein, B[a]P at two concentrations (0.8 μg/L and 2.0 μg/L) were selected to investigate the molecular mechanisms of the affected locomotor behavior of zebrafish by B[a]P based on transcriptome profiling. Adverse effects of B[a]P exposure affecting locomotor behavior in zebrafish were studied by RNA sequencing, and the locomotion phenotype was acquired. The gene enrichment results showed that the differentially highly expressed genes (atp2a1, cdh2, aurka, fxyd1, clstn1, apoc1, mt-co1, tnnt3b, and fads2) of zebrafish are mainly enriched in adrenergic signaling in cardiomyocytes (dre04261) and locomotory behavior (GO:0007626). The movement trajectory plots showed an increase in the locomotor distance and velocity of zebrafish in the 0.8 μg/L group and the opposite in the 2.0 μg/L group. The results showed that B[a]P affects the variety of genes in zebrafish, including motor nerves, muscles, and energy supply, and ultimately leads to altered locomotor behavior.

Petroleum hydrocarbons can serve as a carbon source for marine phytoplankton; so, marine high-acid crude oil pollution events are likely to result in algal outbreaks or harmful algal blooms (HABs) in surface waters. Naphthenic acids (NAs) are the primary acidic component of crude oil, and red tide is of great concern due to its high diffusivity and strong destructive properties. It is important to study the mechanism of the toxic effect of NAs on the typical red tide algae, Heterosigma akashiwo, for the balance and stability of marine algae. The mechanism of NAs’ damage effect was investigated in terms of the antioxidant enzyme activity, cell number, the chlorophyll positive fluorescence parameters, and the cell morphology of microalgae. Experiments confirmed the hormesis of low-concentration (0.5, 2, and 4 mg/L) NAs on Heterosigma akashiwo, and the indicators of high-concentration (8 and 16 mg/L) NA exposures showed inhibition. In this study, the toxic effect of NAs on the target organism showed a clear concentration–dose relationship. The 16 mg/L NAs stress caused severe damage to the morphology and structure of the target biological cells in a short time (96 h), and the population growth decreased. The target organisms showed a staged oxidative stress response to NAs. The behavior in the low-concentration treatment groups showed toxicant excitatory effects on the photosynthetic efficiency and antioxidant enzyme activity of the target organisms. This study provides theoretical and practical data for the development of an important toxicological model of the toxicant’s excitement effects and antioxidant defense mechanisms. In addition, it provides prospective research data for the prediction and avoidance of ecological risk from NA pollution in marine environments.

Parkinson’s disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra compacta. Ferroptosis, a novel form of regulated cell death characterized by iron accumulation and lipid peroxidation, plays a vital role in the death of dopaminergic neurons. However, the molecular mechanisms underlying ferroptosis in dopaminergic neurons have not yet been completely elucidated. NADPH oxidase 4 is related to oxidative stress, however, whether it regulates dopaminergic neuronal ferroptosis remains unknown. The aim of this study was to determine whether NADPH oxidase 4 is involved in dopaminergic neuronal ferroptosis, and if so, by what mechanism. We found that the transcriptional regulator activating transcription factor 3 increased NADPH oxidase 4 expression in dopaminergic neurons and astrocytes in an 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced Parkinson’s disease model. NADPH oxidase 4 inhibition improved the behavioral impairments observed in the Parkinson’s disease model animals and reduced the death of dopaminergic neurons. Moreover, NADPH oxidase 4 inhibition reduced lipid peroxidation and iron accumulation in the substantia nigra of the Parkinson’s disease model animals. Mechanistically, we found that NADPH oxidase 4 interacted with activated protein kinase C α to prevent ferroptosis of dopaminergic neurons. Furthermore, by lowering the astrocytic lipocalin-2 expression, NADPH oxidase 4 inhibition reduced 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced neuroinflammation. These findings demonstrate that NADPH oxidase 4 promotes ferroptosis of dopaminergic neurons and neuroinflammation, which contribute to dopaminergic neuron death, suggesting that NADPH oxidase 4 is a possible therapeutic target for Parkinson’s disease.

This proof-of-concept study examines the feasibility of defining subgroups in psychiatric spectrum disorders by generative embedding, using dynamical system models which infer neuronal circuit mechanisms from neuroimaging data. To this end, we re-analysed an fMRI dataset of 41 patients diagnosed with schizophrenia and 42 healthy controls performing a numerical n-back working-memory task. In our generative-embedding approach, we used parameter estimates from a dynamic causal model (DCM) of a visual–parietal–prefrontal network to define a model-based feature space for the subsequent application of supervised and unsupervised learning techniques. First, using a linear support vector machine for classification, we were able to predict individual diagnostic labels significantly more accurately (78%) from DCM-based effective connectivity estimates than from functional connectivity between (62%) or local activity within the same regions (55%). Second, an unsupervised approach based on variational Bayesian Gaussian mixture modelling provided evidence for two clusters which mapped onto patients and controls with nearly the same accuracy (71%) as the supervised approach. Finally, when restricting the analysis only to the patients, Gaussian mixture modelling suggested the existence of three patient subgroups, each of which was characterised by a different architecture of the visual–parietal–prefrontal working-memory network. Critically, even though this analysis did not have access to information about the patients' clinical symptoms, the three neurophysiologically defined subgroups mapped onto three clinically distinct subgroups, distinguished by significant differences in negative symptom severity, as assessed on the Positive and Negative Syndrome Scale (PANSS). In summary, this study provides a concrete example of how psychiatric spectrum diseases may be split into subgroups that are defined in terms of neurophysiological mechanisms specified by a generative model of network dynamics such as DCM. The results corroborate our previous findings in stroke patients that generative embedding, compared to analyses of more conventional measures such as functional connectivity or regional activity, can significantly enhance both the interpretability and performance of computational approaches to clinical classification.

For single-phase current source converter (SCSC), at least one upper device and one lower device have to be gated on and maintained at any time. Otherwise, an open-circuit of the DC-link current would occur and destroy the devices. In addition, a bulky DC-link inductor is usually required to obtain a smooth DC-link current. To address these issues, this study proposes a novel SCSC with high reliability and high-power density. In the proposed circuit, even all the switches are turned on or turned off simultaneously, neither short-circuit nor open-circuit will happen. The inductance in DC-side is reduced significantly byadopting the active power decoupling technique. First, the operation principle of the proposed converter is introduced in detail. Then, a closed-loop control method is presented to regulate the DC-link current, maintain the DC component of the decoupling capacitor voltage, and achieve sinusoidal grid current. Besides, the parameter design of the circuit and controller is investigated. Moreover, the efficiency comparison between the proposed and other SCSCs is carried out. Finally, the effectiveness of the proposed topology is verified by the experimental results. [ABSTRACT FROM AUTHOR]

Abstract Background Prunus pedunculata Pall, the deciduous shrub of Amygdalus subgenus in Rosaceae, is a new kind of desert oil-bearing tree. It has a long story of being planted in the West and North of China for sand fixation and desert control. In addition, the seeds of P. pedunculata are rich of oil, especially the monounsaturated fatty acid and polyunsaturated fatty acid. However, little is known about the molecular mechanisms of oil accumulation during the seed development of P. pedunculata. Results The seeds of P. pedunculata from three independent plants at 10, 18, 24, 31, 39, 45, 59 and 73 days after flowering (DAF) were obtained and the oil compositions were evaluated. It showed that oleic acid was the dominant type of oil content in the mature seeds (from 32.724% at 10DAF to 72.06% at 73DAF). Next, transcriptome sequencing for the developing seeds produced 988.795 million high quality reads and TRINITY assembled 326,271 genes for the first transcriptome for P. pedunculata. After the assembled transcriptome was evaluated by BUSCO with 85.9% completeness, we identified 195,342, 109,850 and 121,897 P. pedunculata genes aligned to NR, GO and KEGG pathway databases, respectively. Then, we predicted 23,229 likely proteins from the assembled transcriptome and identified 1917 signal peptides and 5512 transmembrane related proteins. In the developing seeds we detected 91,362 genes (average FPKM > 5) and correlation analysis indicated three possible development stages – early (10 ~ 24DAF), middle (31 ~ 45DAF) and late (59 ~ 73DAF). We next analyzed the differentially expressed genes (DEGs) in the developing seeds. Interestingly, compared to 10DAF the number of DEGs was increased from 4406 in 18DAF to 27,623 in 73DAF. Based on the gene annotation, we identified 753, 33, 8 and 645 DEGs related to the fatty acid biosynthesis, lipid biosynthesis, oil body and transcription factors. Notably, GPAT, DGD1, LACS2, UBC and RINO were highly expressed at the early development stage, ω6-FAD, SAD, ACP, ACCA and AHG1 were highly expressed at the middle development stage, and LACS6, DGD1, ACAT1, AGPAT, WSD1, EGY2 and oleosin genes were highly expressed at the late development stage. Conclusions This is the first time to study the developing seed transcriptome of P. pedunculata and our findings will provide a valuable resource for future studies. More importantly, it will improve our understanding of molecular mechanisms of oil accumulation in P. pedunculata.

Foreground/background (fg/bg) classification is an important first step for several video analysis tasks such as people counting, activity recognition and anomaly detection. As is the case for several other Computer Vision problems, the advent of deep Convolutional Neural Network (CNN) methods has led to major improvements in this field. However, despite their success, CNN-based methods have difficulties in coping with multi-scene videos where the scenes change multiple times along the time sequence. In this paper, we propose a deep features fusion network based foreground segmentation method (DFFnetSeg), which is both robust to scene changes and unseen scenes comparing with competitive state-of-the-art methods. In the heart of DFFnetSeg lies a fusion network that takes as input deep features extracted from a current frame, a previous frame, and a reference frame and produces as output a segmentation mask into background and foreground objects. We show the advantages of using a fusion network and the three frames group in dealing with the unseen scene and bootstrap challenge. In addition, we show that a simple reference frame updating strategy enables DFFnetSeg to be robust to sudden scene changes inside video sequences and prepare a motion map based post-processing method which further reduces false positives. Experimental results on the test dataset generated from CDnet2014 and Lasiesta demonstrate the advantages of the DFFnetSeg method.

Alternative pre-mRNA splicing (AS) is prevalent in plants and is involved in many interactions between plants and environmental stresses. However, the patterns and underlying mechanisms of AS evolution in plants remain unclear. By analyzing the transcriptomes of four eudicot species, we revealed that the divergence of AS is largely due to the gains and losses of AS events among orthologous genes. Furthermore, based on a subset of AS, in which AS can be directly associated with specific transcripts, we found that AS that generates transcripts containing premature termination codons (PTC), are likely more conserved than those that generate non-PTC containing transcripts. This suggests that AS coupled with nonsense-mediated decay (NMD) might play an important role in affecting mRNA levels post-transcriptionally. To understand the mechanisms underlying the divergence of AS, we analyzed the key determinants of AS using a machine learning approach. We found that the presence/absence of alternative splice site (SS) within the junction, the distance between the authentic SS and the nearest alternative SS, the size of exon–exon junctions were the major determinants for both alternative 5′ donor site and 3′ acceptor site among the studied species, suggesting a relatively conserved AS mechanism. The comparative analysis further demonstrated that variations of the identified AS determinants significantly contributed to the AS divergence among closely related species in both Solanaceae and Brassicaceae taxa. Together, these results provide detailed insights into the evolution of AS in plants.

The foreground segmentation method is a crucial first step for many video analysis methods such as action recognition and object tracking. In the past five years, convolutional neural network based foreground segmentation methods have made a great breakthrough. However, most of them pay more attention to stationary cameras and have constrained performance on the pan–tilt–zoom (PTZ) cameras. In this paper, an end-to-end deep features homography transformation and fusion network based foreground segmentation method (HTFnetSeg) is proposed for surveillance videos recorded by PTZ cameras. In the kernel of HTFnetSeg, there is the combination of an unsupervised semantic attention homography estimation network (SAHnet) for frames alignment and a spatial transformed deep features fusion network (STDFFnet) for segmentation. The semantic attention mask in SAHnet reinforces the network to focus on background alignment by reducing the noise that comes from the foreground. STDFFnet is designed to reuse the deep features extracted during the semantic attention mask generation step by aligning the features rather than only the frames, with a spatial transformation technique in order to reduce the algorithm complexity. Additionally, a conservative strategy is proposed for the motion map based post-processing step to further reduce the false positives that are brought by semantic noise. The experiments on both CDnet2014 and Lasiesta show that our method outperforms many state-of-the-art methods, quantitively and qualitatively.

We propose a modified integral controller to treat actuation biases in nonholonomic systems. In such systems, although one cannot directly counter biases along all directions, one can still aim at restoring the symmetry of coordinated motion that the biases would break. Focusing on the example of steering controlled planar vehicles, we indeed show how to perfectly stabilize a circular trajectory coordinated with the leader, despite any unknown actuation bias. The proposed solution is a simple modified integral control term, and we prove via a detailed analysis of averaging theory that this control gadget globally stabilizes the perfect coordinated motion. The corresponding general observation is that stabilizing such symmetry-preserving situation can be viewed as rejecting a bias affecting the output measurement, instead of the input command. The symmetry-restoring control then becomes an output bias rejection, dual to the more standard input bias rejection with standard integral control.

Herbivore-induced defenses are widespread, rapidly evolving and relevant for plant fitness. Such induced defenses are often mediated by early defense signaling (EDS) rapidly activated by the perception of herbivore associated elicitors (HAE) that includes transient accumulations of jasmonic acid (JA). Analyzing 60 HAE-induced leaf transcriptomes from closely-related Nicotiana species revealed a key gene co-expression network (M4 module) which is co-activated with the HAE-induced JA accumulations but is elicited independently of JA, as revealed in plants silenced in JA signaling. Functional annotations of the M4 module were consistent with roles in EDS and a newly identified hub gene of the M4 module (NaLRRK1) mediates a negative feedback loop with JA signaling. Phylogenomic analysis revealed preferential gene retention after genome-wide duplications shaped the evolution of HAE-induced EDS in Nicotiana. These results highlight the importance of genome-wide duplications in the evolution of adaptive traits in plants.

The wine and beer yeast Dekkera bruxellensis thrives in environments that are harsh and limiting, especially in concentrations with low oxygen and high ethanol. Its different strains' chromosomes greatly vary in number (karyotype). This study isolates two novel centromeric loci (CEN1 and CEN2), which support both the yeast's autonomous replication and the stable maintenance of plasmids. In the sequenced genome of the D. bruxellensis strain CBS 2499, CEN1 and CEN2 are each present in one copy. They differ from the known "point" CEN elements, and their biological activity is retained within ~900-1300 bp DNA segments. CEN1 and CEN2 have features of both "point" and "regional" centromeres: They contain conserved DNA elements, ARSs, short repeats, one tRNA gene, and transposon-like elements within less than 1 kb. Our discovery of a miniature inverted-repeat transposable element (MITE) next to CEN2 is the first report of such transposons in yeast. The transformants carrying circular plasmids with cloned CEN1 and CEN2 undergo a phenotypic switch: They form fluffy colonies and produce three times more biofilm. The introduction of extra copies of CEN1 and CEN2 promotes both genome rearrangements and ploidy shifts, with these effects mediated by homologous recombination (between circular plasmid and genome centromere copy) or by chromosome breakage when integrated. Also, the proximity of the MITE-like transposon to CEN2 could translocate CEN2 within the genome or cause chromosomal breaks, so promoting genome dynamics. With extra copies of CEN1 and CEN2, the yeast's enhanced capacities to rearrange its genome and to change its gene expression could increase its abilities for exploiting new and demanding niches.