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In the realistic world, various individuals have distinct personalities, preferences, and attitudes toward new information and behavior acceptance, called population heterogeneity. It is seldom taken into account and theoretically analyzed in information propagation on a weighted network. Therefore, we divide individuals into fashionable and conservative individuals according to their passion degree and willingness for novel behaviors acceptance. Then, we build two behavior adoption threshold models corresponding to fashionable and conservative individuals on the weighted network to explore the effect of population heterogeneity on information propagation. Next, a partition theory based on edge weight and population heterogeneity is proposed to qualitatively analyze the information propagation mechanism. The theoretical analyses and simulation results show that fashionable individuals promote information propagation and behavior adoption. More importantly, the crossover phenomena of phase transition appear. When the fraction of fashionable individuals is relatively large, the increasing pattern of the final adoption size shows a second-order continuous phase transition. In comparison, the increasing pattern alters to first-order discontinuous phase transition with the decrease of the fraction of fashionable individuals. Moreover, reducing weight distribution heterogeneity promotes information propagation and slightly accelerates the change of the phase transition pattern from the first-order discontinuous to the second-order continuous. Besides, increasing the degree distribution heterogeneity accelerates the change of the phase transition pattern. Finally, our theoretical analyses coincide well with the simulation results.

Seismic behavior of a structure is directly related to its dynamic characteristics, which include natural frequency, damping ratio, and mode shape. This study focuses on the long-term monitoring of dynamic characteristics of six selected target structures. The covariance-driven stochastic subspace identification (SSI) approach is used to estimate the fundamental natural frequency and damping ratio of target buildings based on long-term motion records in order to examine the temporal variation of dynamic properties. The fundamental natural frequency and damping ratio variations over time are first discussed. It is found that the fundamental natural frequency of some structures reduces dramatically after the 2011 Tohoku Earthquake, accompanied by a rise in damping ratio. Then, regression analysis is used to assess the relationship between dynamic characteristics and ground motion parameters (Peak ground acceleration (PGA), magnitude, focal depth, and epicentral distance) and structural response (root mean square acceleration, maximum response amplitude). It is discovered that the identified natural frequency has no clear correlation with the focal depth, a slight negative correlation with the epicentral distance, and a strong negative correlation with the magnitude and PGA. The root mean square acceleration and the maximum response amplitude are negatively correlated to the target buildings’ natural frequencies. Finally, the influence of environmental factors on dynamic properties is investigated.

Background: Lung adenocarcinoma (LUAD) is the major form of lung cancer that presents a major peril to public health. Owing to the high rates of morbidity, mortality and chemoresistance, it is necessary to develop more effective therapeutic targets of LUAD. Mitochondrial fission regulator 1 (MTFR1) affects the occurrence and development of some diseases by regulating mitochondrial dynamics and is dysregulated in LUAD. However, the functions and molecular mechanisms of MTFR1 in LUAD have not been investigated.Methods: Immunohistochemical (IHC) analysis, real-time quantitative polymerase chain reaction (RT-qPCR), bioinformatic analysis and western blot (WB) were performed to assess the expression of MTFR1 at both protein and mRNA levels. The biological functions of MTFR1 in LUAD cells were assessed based on various in vivo and in vitro experiments. The dual-luciferase reporter assay and some rescue experiments were performed to evaluate the underlying mechanism of MTFR1 in LUAD.Results: MTFR1 was upregulated in LUAD cells and tissues and correlated with dismal clinicopathologic features and a worse prognosis of patients with LUAD. Functionally, MTFR1 overexpression stimulated the proliferation, invasion, migration and glycolytic capacity and impeded the apoptosis of LUAD cells; however, opposite results were obtained when MTFR1 expression was knocked down. MTFR1, which was directly targeted by miR-29c-3p, may exert its biological functions through the AMPK/mTOR signalling pathway.Conclusion: MTFR1 promotes the progression of LUAD. Therefore, targeting MTFR1 can offer an effective therapeutic strategy for LUAD treatment.

How structures, e.g., magnetic loops, in the upper atmosphere, i.e., the transition region and corona, are heated and sustained is one of the major unresolved issues in solar and stellar physics. Various theoretical and observational studies on the heating of coronal loops have been undertaken. The heating of quiescent loops caused by eruptions, however, is rarely observed. In this study, employing data from the Solar Dynamics Observatory (SDO) and Solar Upper Transition Region Imager (SUTRI), we report the heating of quiescent loops associated with nearby eruptions. In active regions (ARs) 13092 and 13093, a long filament and a short filament, and their overlying loops, were observed on 2022 September 4. In AR 13093, a warm channel erupted toward the northeast, whose material moved along its axis toward the northwest under the long filament, turned to the west above the long filament, and divided into two branches falling to the solar surface. Subsequently, the short filament erupted toward the southeast. Associated with these two eruptions, the quiescent loops overlying the long filament appeared in SDO/Atmospheric Imaging Assembly (AIA) high-temperature images, indicating the heating of loops. During the heating, the signature of magnetic reconnection between loops is identified, including the inflowing motions of loops, and the formation of X-type structures and newly reconnected loops. The heated loops then cooled down. They appeared sequentially in AIA and SUTRI lower-temperature images. All the results suggest that the quiescent loops are heated by reconnection between loops caused by the nearby warm channel and filament eruptions.

Coronal mass ejections (CMEs) are violent ejections of magnetized plasma from the Sun that can trigger geomagnetic storms, endanger satellite operations, and destroy electrical infrastructures on the Earth. After systematically searching Sun-as-a-star spectra observed by the Extreme Ultraviolet Variability Experiment on board the Solar Dynamics Observatory (SDO) from 2010 May to 2022 May, we identified eight CMEs associated with flares and filament eruptions by analyzing the blue-wing asymmetry of the O iii 52.58 nm line profiles. Combined with images simultaneously taken by the 30.4 nm channel of the Atmospheric Imaging Assembly on board SDO, the full velocity and propagation direction for each of the eight CMEs are derived. We find a strong correlation between geomagnetic indices ( Kp and Dst) and the angle between the CME propagation direction and the Sun–Earth line, suggesting that Sun-as-a-star spectroscopic observations at extreme-ultraviolet wavelengths can potentially help to improve the prediction accuracy of the geoeffectiveness of CMEs. Moreover, an analysis of synthesized long-exposure Sun-as-a-star spectra implies that it is possible to detect CMEs from other stars through blue-wing asymmetries or blueshifts of spectral lines.

Type II radio bursts are often associated with coronal shocks that are typically driven by coronal mass ejections (CMEs) from the Sun. Here we conduct a case study of a type II radio burst that is associated with a C4.5-class flare and a blowout jet, but without the presence of a CME. The blowout jet is observed near the solar disk center in the extreme-ultraviolet (EUV) passbands with different characteristic temperatures. Its evolution involves an initial phase and an ejection phase with a velocity of 560 ± 87 km s ^−1 . Ahead of the jet front, an EUV wave propagates at a projected velocity of ∼403 ± 84 km s ^−1 in the initial stage. The velocity of the type II radio burst is estimated to be ∼641 km s ^−1 , which corresponds to the shock velocity against the coronal density gradient. The EUV wave and the type II radio burst are closely related to the ejection of the blowout jet, suggesting that both are likely the manifestation of a coronal shock driven by the ejection of the blowout jet. The type II radio burst likely starts lower than those associated with CMEs. The combination of the velocities of the radio burst and the EUV wave yields a modified shock velocity at ∼757 km s ^−1 . The Alfvén Mach number is in the range of 1.09–1.18, implying that the shock velocity is 10%–20% larger than the local Alfvén velocity.

Partial filament eruptions have often been observed; however, the physical mechanisms that lead to filament splitting are not yet fully understood. In this study, we present a unique event of a partial filament eruption that undergoes two distinct splitting processes. The first process involves vertical splitting and is accompanied by brightenings inside the filament, which may result from internal magnetic reconnection within the filament. Following the first splitting process, the filament is separated into an upper part and a lower part. Subsequently, the upper part undergoes a second splitting, which is accompanied by a coronal blowout jet. An extrapolation of the coronal magnetic field reveals a hyperbolic flux tube structure above the filament, indicating the occurrence of breakout reconnection that reduces the constraining field above. Consequently, the filament is lifted up, but at a nonuniform speed. The high-speed part reaches the breakout current sheet to generate the blowout jet, while the low-speed part falls back to the solar surface, resulting in the second splitting. In addition, continuous brightenings are observed along the flare ribbons, suggesting the occurrence of a slipping reconnection process. This study presents, for the first time, the unambiguous observation of a two-stage filament-splitting process, advancing our understanding of the complex dynamics of solar eruptions.

Recent observations have revealed two types of decayless transverse oscillations in short coronal loops: one with short periods scaling with loop lengths, and the other with longer periods that exhibit a peak at around 5 minutes in the period distribution. To understand such a difference in period, we work in the framework of ideal MHD and model a short coronal loop embedded in an atmosphere with density stratification from the chromosphere to the corona. An inclined p-mode-like driver with a period of 5 minutes is launched at one loop footpoint. It is discovered that two types of decayless transverse oscillations can be excited in the loop. We interpret the 5 minutes periodicity as being directly driven by the footpoint driver, while the others, with periods of several tens of seconds, are regarded as kink eigenmodes of different harmonics. Therefore, our simulation shows that both types of decayless oscillations found in observations can be excited by p-modes in one short coronal loop. This study extends our understanding of ubiquitous decayless transverse oscillations in the corona. Furthermore, it suggests that p-modes could be an important energy source for coronal heating by driving decayless transverse oscillations.

Radio bursts from nearby active M-dwarfs have been frequently reported and extensively studied in solar or planetary paradigms. Whereas, their substructures or fine structures remain rarely explored despite their potential significance in diagnosing the plasma and magnetic field properties of the star. Such studies in the past have been limited by the sensitivity of radio telescopes. Here we report the inspiring results from the high time-resolution observations of a known flare star AD Leo with the Five-hundred-meter Aperture Spherical radio Telescope. We detected many radio bursts in the 2 days of observations with fine structures in the form of numerous millisecond-scale sub-bursts. Sub-bursts on the first day display stripe-like shapes with nearly uniform frequency drift rates, which are possibly stellar analogs to Jovian S-bursts. Sub-bursts on the second day, however, reveal a different blob-like shape with random occurrence patterns and are akin to solar radio spikes. The new observational results suggest that the intense emission from AD Leo is driven by electron cyclotron maser instability, which may be related to stellar flares or interactions with a planetary companion.

Analytical target cascading (ATC) is a method for coordinating hierarchical system design optimization with a decomposition-based framework. Since a launch vehicle (LV) is usually powered by two or more stages of rocket motors, the overall design of the LV clearly has a hierarchical structure, including system level (conducted by the general design department) and subsystem level (conducted by the motor stage design department). In particular, the subsystem level contains stage-divided elements rather than discipline-divided elements. Therefore, ATC is inherently suitable for the overall design of the LV. This paper presents an ATC decomposition framework for LV design according to practical engineering. The feasibility of the multi-island genetic algorithm (MIGA) used in the ATC decomposition is verified by a mathematical programming test, in which non-linear programming with the quadratic Lagrangian (NLPQL) algorithm is set as a comparison. The multi-disciplinary analysis modules of a hybrid rocket motor (HRM) propelled LV, including propulsion, structure, aerodynamics and trajectory, are established. A hierarchical decomposition is proposed for this multi-level design with a multi-disciplinary model. The application and optimization results verify the feasibility of the ATC decomposition framework with MIGA in the preliminary design of the LV and the final orbit accuracy is better than that of the MDF method. In addition, the final design schemes also prove that HRMs can be considered as a feasible choice of propulsion system for a small payload at low earth orbit.

Catalytic hybrid rocket motors using hydrogen peroxide (HP) are easy and efficient to achieve multiple starts and stops, and hydroxyl-terminated polybutadiene (HTPB) grains are commonly used due to their excellent mechanical properties. The low regression rate of HTPB grains limits the application of hybrid rocket motors. Furthermore, the addition of solid aluminum particles can effectively improve the regression rate and performance of hybrid rocket motors. However, the experimental results of a high mass fraction of aluminum and hydrogen peroxide available at present are not sufficient. In this research, the impact of a high mass fraction of aluminum on the motor performance and ablation rate of nozzles is studied experimentally. A solution of 95% hydrogen peroxide and HTPB with an aluminum additive are adopted as propellants. The variation in the axial regression rate of the grains is obtained by computed tomography (CT) scans and pre-test parameter measurements. The instantaneous regression rate method is adopted to obtain the real-time regression rate of the motor. The surface appearance and composition of the front and the end of the grains after the tests are analyzed by electron microscopy. Carbon ceramic and tungsten-bronze nozzles are used to explore the effect of a high mass fraction of aluminum on nozzle ablation. The experimental results show that the addition of aluminum raises the specific impulse and decreases the optimal oxygen-to-fuel ratio of the propellant combination. The high mass fraction of the aluminum particles has a severe ablative effect on carbon ceramic nozzles, while the effect on tungsten-bronze nozzles is minimal for a hot test lasting four to five seconds. Our results can provide experimental guidance for the application of a high mass fraction of aluminum and hydrogen peroxide hybrid rocket motor.

Near-surface energy budget closure has been a trending topic in land surface processes research, especially on the underlying surfaces of heterogeneous wetlands. In this investigation, the horizontal thermal advection caused by thermal inhomogeneity over the alpine wetland is calculated based on the eddy covariance data observed at the Flower Lake observation field and WRF modelling data over the Zoige alpine wetland, China. The contribution of horizontal thermal advection to the near-surface energy closure is analysed. The results show that the mean horizontal heat advection of the Zoige wetland is 20.2 W·m−2, and the maximum value reached 55.0 W·m−2 in the summer of 2017. After introducing thermal advection into the near-surface energy balance equation, the near-surface energy closure ratio increased from 72.3% to 81.0%.

Polyaspartic acid (PASP) is a macromolecule compound with carboxylic acid side chains which is polymerized by L-aspartic acid, has been used as a biodegradable and environmentally-friendly chelating agent to enhance the phytoremediation of heavy metal-contaminated soils. Cadmium (Cd) is a toxic element for plant growth, productivity, and food security. To reveal the responses of PASP to plant physiology and morphology under Cd stress, we comprehensively analyzed soil characteristics, cell ultrastructure, reactive oxygen species (ROS), antioxidant enzymes, Cd uptake, transport, subcellular distribution, cell wall compositions, and their Cd chelating capacity in rapeseed. The results showed PASP increased the content of total N, total P, and available P in soil by 3.4%, 28.6%, and 39.8%, respectively, but did not change soil pH and available Cd. Meanwhile, PASP promoted dry mass accumulation and increased photosynthetic pigment content in rapeseed leaves by maintaining the chloroplast structure. Lower malondialdehyde (MDA) content and hydrogen peroxide (H2O2) accumulation and activated antioxidant enzymes in leaves indicate that PASP contributed to relieving Cd-induced oxidative damage to cells of rapeseed leaves. The results indicated that PASP application increased the Cd distribution ratio in root cell walls from 47.4% to 62.3% and decreased the Cd content in xylem sap by 37.8%, which ultimately reduced Cd reallocation in leaves. Additionally, higher pectin content and Cd in pectin resulted in higher Cd retention in leaf cell walls while reducing its concentration in the organelle fraction. The results indicated that 0.3% PASP effectively alleviated Cd stress in rapeseed leaves by inhibiting Cd transportation from roots, activating antioxidant enzymes to scavenge ROS, and promoting Cd chelation by cell wall pectin in leaves.

Objective: To describe the frequency and spectrum of treatment-related adverse events (TRAEs) of immunotherapy combined with antiangiogenic therapy in patients with melanoma.Methods: This retrospective cohort study included three clinical trials on patients with stage III/IV melanoma treated with anti–PD 1 and antiangiogenic therapy.Results: We analyzed data from 72 patients with a median follow-up time of 25.9 months (95% CI, 9.1–42.7 m). The median treatment duration was 7.5 months (range, 0.7–42.8 m), and the median of treatment cycles was 11.0 (range, 1–90). Most patients (70 of 72 or 97.2%) experienced TRAEs (mostly grades 1 or 2). No drug-related deaths were reported. Most TRAEs were hepatic (75%), endocrine (72.2%), skin (65.3%), and gastrointestinal tract (59.7%) manifestations, followed by myelosuppression (55.6%), renal dysfunction (55.6%), and dyslipidaemia (54.2%). The adverse event (AE) spectra were similar between regimens. Using multivariate Cox proportional risk models showed that hypertension was associated with a long PFS. According to our multivariable logistic regression models, TRAEs were not associated with ORR.Conclusion: We found that the prevalence of AEs was higher than that of anti–PD-1 monotherapy. Most of the AEs were mild. The AE spectra were similar to those seen after anti–PD-1 or antiangiogenic therapy monotherapy, without unexpected AEs. Immunotherapy combined with antiangiogenic therapy was well tolerated.Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03955354.

BackgroundFerroptosis is a novel form of regulated cell death involved in tumor progression. The role of ferroptosis-related lncRNAs in hepatocellular carcinoma (HCC) remains unclear.MethodsRNA-seq and clinical data for HCC patients were downloaded from The Cancer Genome Atlas (TCGA) Genomic Data Commons (GDC) portal. Bioinformatics methods, including weighted gene coexpression network analysis (WGCNA), Cox regression, and least absolute shrinkage and selection operator (LASSO) analysis, were used to identify signature markers for diagnosis/prognosis. The tumor microenvironment, immune infiltration and functional enrichment were compared between the low-risk and high-risk groups. Subsequently, small molecule drugs targeting ferroptosis-related signature components were predicted via the L1000FWD and PubChem databases.ResultsThe prognostic model consisted of 2 ferroptosis-related mRNAs (SLC1A5 and SLC7A11) and 8 ferroptosis-related lncRNAs (AC245297.3, MYLK-AS1, NRAV, SREBF2-AS1, AL031985.3, ZFPM2-AS1, AC015908.3, MSC-AS1). The areas under the curves (AUCs) were 0.830 and 0.806 in the training and test groups, respectively. Decision curve analysis (DCA) revealed that the ferroptosis-related signature performed better than all pathological characteristics. Multivariate Cox regression analysis showed that the risk score was an independent prognostic factor. The survival probability of low- and high-risk patients could be clearly distinguished by the principal component analysis (PCA) plot. The risk score divided HCC patients into two distinct groups in terms of immune status, especially checkpoint gene expression, which was further supported by the Gene Ontology (GO) biological process, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Finally, several small molecule drugs (SIB-1893, geldanamycin and PD-184352, etc) targeting ferroptosis-related signature components were identified for future reference.ConclusionWe constructed a new ferroptosis-related mRNA/lncRNA signature for HCC patients. The model can be used for prognostic prediction and immune evaluation, providing a reference for immunotherapies and targeted therapies.

Abstract Background Atrioesophageal fistula (AEF) is the most fatal complication associated with catheter ablation for atrial fibrillation and cannot be easily detected when thoracic contrast-enhanced computed tomography (CT) is normal. Case presentation In this report, we described a diagnostic tool for detecting AEF with doubtful chest CT in which we introduced CO2-insufflation esophageal endoscopy with transthoracic echocardiography monitoring. Using this modified esophageal endoscopy, AEF was established due to the presence of both esophageal lesions and bubbles into the left atrium. That way, our patient accepted to be operated in time with good clinical prognosis. Conclusions This modified esophageal endoscopy is an alternative tool for early detection of AEF when normal or doubtful CT findings present.

Abstract In a previous study, we developed Pichia pastoris GS115m, an engineered strain with decreased expression of one key gene, LRA4, in rhamnose metabolism. P. pastoris GS115m/LacB was subsequently constructed via introducing a β-galactosidase gene, LacB, under the control of rhamnose-inducible P LRA3 into P. pastoris GS115m. P. pastoris GS115m/LacB greatly improved recombinant protein production relative to the parental strain (P. pastoris GS115/LacB). In the present study, transcriptomes of P. pastoris GS115m/LacB and P. pastoris GS115/LacB grown in YPR medium were analyzed. P. pastoris GS115m/LacB was found to suffer from the mild carbon source starvation. To attenuate the starvation stress, P. pastoris GS115m/LacB attempted to enhance rhamnose metabolism by elevating the transcription levels of rhamnose-utilization genes LRA1-3 and RhaR. The transcription level of LacB under the control of P LRA3 thereby increased, resulting in the improved production of recombinant protein in P. pastoris GS115m/LacB. It was also revealed that P. pastoris GS115m/LacB cells coped with carbon starvation mostly via autophagy.

The emergence of mobile Internet of Things (IoT) has brought much more convenience to our daily life than ever before, modern intelligent vehicles are usually equipped with various mobile IoT components or devices. However, when we are enjoying the convenience from the rapid development of mobile IoT services, our privacy can be misused by attackers in an easier way. In this paper, we devise a query scheme with intelligent vehicle privacy guarantees, which enables a vehicle to acquire accurate query service from the service provider (SP) without providing its explicit private information, such as location or query interest privacy. And more than that, we introduce network coding for the first time to make our scheme applicable to a more sophisticated top-K query by multiple vehicles cooperation in mobile IoT. Furthermore, we also consider the unnecessary reveal issue of service data at SP side since the data is its asset. Performance analysis and experiments verify the validity of our scheme and demonstrate a better accuracy and efficiency compared with existing solutions in mobile IoT scenario.

Abstract Background MicroRNAs (miRNAs) and Twist1-induced epithelial-mesenchymal transition (EMT) in cancer cell dissemination are well established, but the involvement of long noncoding RNAs (lncRNAs) in Twist1-mediated signaling remains largely unknown. Methods RT-qPCR and western blotting were conducted to detect the expression levels of lncRNA JPX and Twist1 in lung cancer cell lines and tissues. The impact of JPX on Twist1 expression, cell growth, invasion, apoptosis, and in vivo tumor growth were investigated in lung cancer cells by western blotting, rescue experiments, colony formation assay, flow cytometry, and xenograft animal experiment. Results We observed that lncRNA JPX was upregulated in lung cancer metastatic tissues and was closely correlated with tumor size and an advanced stage. Functionally, JPX promoted lung cancer cell proliferation in vitro and facilitated lung tumor growth in vivo. Additionally, JPX upregulated Twist1 by competitively sponging miR-33a-5p and subsequently induced EMT and lung cancer cell invasion. Interestingly, JPX and Twist1 were coordinately upregulated in lung cancer tissues and cells. Mechanically, the JPX/miR-33a-5p/Twist1 axis participated in EMT progression by activating Wnt/β-catenin signaling. Conclusions These findings suggest that lncRNA JPX, a mediator of Twist1 signaling, could predispose lung cancer cells to metastasis and may serve as a potential target for targeted therapy.

Many real-world phenomena can be described as complex contagions, which has attracted much attention in the field of network science. However, the effects of the heterogeneous adoption thresholds on complex contagions in weighted networks have not been systematically investigated. In this paper, we propose a heterogeneous complex contagion model on the weighted network, in which individuals have different adoption thresholds. For individuals with a relatively small adoption threshold, they are more likely to adopt the contagion and act as activists. An edge-weight based compartmental theory is developed to unveil spreading dynamics. Through extensive numerical simulations and theoretical analysis, we find that, for any weight distribution heterogeneity, with the increase of the activist fraction, the growth pattern of the final adoption size versus the information spreading probability changes from hybrid phase transition to a second-order continuous phase transition. Meanwhile, increasing the activist fraction can promote behavior spreading. Through bifurcation analysis, we discover that changing the heterogeneity of the weight distribution will not change the type of phase transition. Besides, reducing weight distribution heterogeneity can facilitate behavior spreading. Extensive numerical simulations verify that the theoretical solutions coincide with the numerical results very well.

Steganography in inactive Voice-over-IP frames is a new technique of information hiding, which can achieve large steganographic capacity while maintaining excellent imperceptibility. To prevent the illegitimate use of this technique, the entropy-based and poker test-based steganalysis methods have been presented. However, the detection performance of these two methods is not so good for the cases of having small quantity of inactive frames or low embedding rates. Thus, we present a new steganalysis method based on statistic characteristics of fundamental frequency. Specifically, we employ the statistics for zero-crossing count (ZCC), including the average ZCC of inactive frames, the ratio between the average ZCC of inactive frames and that of all frames, and the difference between the average ZCC of inactive frames and their calibrated versions, to characterize the frame-level dynamic characteristic of speech signals; we utilize the average values of Mel-frequency cepstral coefficients (MFCCs) to represent the invariant characteristic of inactive frames; further, using the feature set consisting of the zero-crossing statistics and average MFCCs, we propose a support-vector-machine based steganalysis for inactive speech frames. The proposed steganalysis method is evaluated with a large number of ITU-T G.723.1 encoded speech samples, and compared with the existing methods. The experimental results demonstrate that the proposed method significantly outperforms the previous ones on detection accuracy, false positive rate and false negative rate for any given embedding rates or using the same number of inactive frames. Particularly, the proposed method can provide accurate detecting results for the existing steganographic methods only using very small quantity of inactive frames, and thereby be employed to detecting potential inactive-frame steganography behaviors in real-time speech streams.

The convergence of wireless power transfer (WPT) and mobile edge computing (MEC) has fostered the rise of wireless powered MEC, which is taken as a crucial technology for the sustainability of the Industrial Internet of Things (IIoT) systems. This article provides an overview of wireless powered MEC enabled IIoT systems, including use cases, network requirements, system architecture, and resource management. First, we highlight four key requirements to drive operational efficiency from the perspective of being transformed IIoT projects. Then an integration architecture of wireless powered MEC for IIoT is proposed. Designed with joint consideration of energy, communication, and computing resources, the architecture is enabled by an efficient system schedule mechanism to achieve age-aware data update, green and sustainable energy supply, as well as hierarchical and resilient computation. Finally, a case study is provided to verify the feasibility of the proposed architecture and demonstrate the efficiency of the proposed resource management approach.

Taccalonolide A has been reported to have anti-tumour efficiency. However, the underlying mechanism for taccalonolides A therapy of hepatocellular carcinoma (HCC) is still obscure. Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. Apoptosis was determined by flow cytometry. Protein expression of B cell lymphoma (Bcl-2), Bcl-2 associated X (Bax), sonic hedgehog (Shh), Smoothened (Smo) and Gli family zinc finger 1 (Gli1) was analyzed by western blot. The expression of Shh, Smo and Gli1 mRNA was determined using quantitative real-time polymerase chain reaction (qRT-PCR). Results showed that taccalonolide A inhibited cell proliferation, induced apoptosis and cell cycle arrest at the G0/G1 phase, and improved the cytotoxicity of sorafenib in HCC cells. The expressions of Shh, Smo, Gli1 mRNA and protein were decreased after taccalonolide A treatment. More importantly, activation of the Shh pathway attenuated taccalonolide A-induced inhibition on cell viability and promotion on apoptosis and cell cycle arrest in HCC. Also, activation of the Shh pathway neutralized the effect of taccalonolide A on sorafenib cytotoxicity in HCC. We clarified that taccalonolide A suppressed cell viability facilitated apoptosis, and improved the cytotoxicity of sorafenib in HCC by inhibition of the activation of the Shh pathway, providing alternative treatments for HCC.

During fungal infections, plant cells secrete chitinases, which digest chitin in the fungal cell walls. The recognition of released chitin oligomers via lysin motif (LysM)-containing immune host receptors results in the activation of defense signaling pathways. We report here that Verticillium nonalfalfae, a hemibiotrophic xylem-invading fungus, prevents these digestion and recognition processes by secreting a carbohydrate-binding motif 18 (CBM18)-chitin-binding protein, VnaChtBP, which is transcriptionally activated specifically during the parasitic life stages. VnaChtBP is encoded by the Vna8.213 gene, which is highly conserved within the species, suggesting high evolutionary stability and importance for the fungal lifestyle. In a pathogenicity assay, however, Vna8.213 knockout mutants exhibited wilting symptoms similar to the wild-type fungus, suggesting that Vna8.213 activity is functionally redundant during fungal infection of hop. In a binding assay, recombinant VnaChtBP bound chitin and chitin oligomers in vitro with submicromolar affinity and protected fungal hyphae from degradation by plant chitinases. Moreover, the chitin-triggered production of reactive oxygen species from hop suspension cells was abolished in the presence of VnaChtBP, indicating that VnaChtBP also acts as a suppressor of chitin-triggered immunity. Using a yeast-two-hybrid assay, circular dichroism, homology modeling, and molecular docking, we demonstrated that VnaChtBP forms dimers in the absence of ligands and that this interaction is stabilized by the binding of chitin hexamers with a similar preference in the two binding sites. Our data suggest that, in addition to chitin-binding LysM (CBM50) and Avr4 (CBM14) fungal effectors, structurally unrelated CBM18 effectors have convergently evolved to prevent hydrolysis of the fungal cell wall against plant chitinases and to interfere with chitin-triggered host immunity.

Steganography is a promising technique for covert communications. However, illegal United States of Americage of this technique would facilitate cybercrime activities and thereby pose a great threat to information security. Therefore, it is crucial to study its countermeasure, namely, steganalysis. In this paper, we aim to present an efficient steganalysis method for detecting adaptive-codebook based steganography in adaptive multi-rate (AMR) speech streams. To achieve this goal, we first design a new low-dimensional feature set for steganalysis, including an improved calibrated Markov transition probability matrix for the second-order difference of pitch delay values (IC-MSDPD) and the probability distribution of the odevity for pitch delay values (PDOEPD). The dimension of the proposed feature set is 14, far smaller than the feature set in the state-of-the-art steganalysis method. Employing the new feature set, we further present a steganalysis scheme for AMR speech based on support vector machines. The presented scheme is evaluated with a large number of AMR-encoded speech samples, and compared with the state-of-the-art one. The experimental results show that the proposed method is effective, and outperforms the state-of-the-art one in both detection accuracy and computational overhead.

Fibroblast growth factor (FGF)19, an endocrine hormone produced in the gut, acts in the liver to control bile acid synthesis. NGM282, an engineered FGF19 analog, is currently in clinical development for treating nonalcoholic steatohepatitis. However, the molecular mechanisms that integrate FGF19 with cholesterol metabolic pathways are incompletely understood. Here, we report that FGF19 and NGM282 promote HDL biogenesis and cholesterol efflux from the liver by selectively modulating LXR signaling while ameliorating hepatic steatosis. We further identify ABCA1 and FGF receptor 4 as mediators of this effect, and that administration of a HMG-CoA reductase inhibitor or a blocking antibody against proprotein convertase subtilisin/kexin type 9 abolished FGF19-associated elevations in total cholesterol, HDL cholesterol (HDL-C), and LDL cholesterol in db/db mice. Moreover, we show that a constitutively active MEK1, but not a constitutively active STAT3, mimics the effect of FGF19 and NGM282 on cholesterol change. In dyslipidemic Apoe−/− mice fed a Western diet, treatment with NGM282 dramatically reduced atherosclerotic lesion area in aortas. Administration of NGM282 to healthy volunteers for 7 days resulted in a 26% increase in HDL-C levels compared with placebo. These findings outline a previously unrecognized role for FGF19 in the homeostatic control of cholesterol and may have direct impact on the clinical development of FGF19 analogs.

Abstract Background Oxaliplatin resistance is a major challenge for treatment of advanced colorectal cancer (CRC). Both acquisition of epithelial-mesenchymal transition (EMT) and suppressed drug accumulation in cancer cells contributes to development of oxaliplatin resistance. Aberrant expression of small noncoding RNA, miR-128-3p, has been shown to be a key regulator in tumorigenesis and cancer development. However, its roles in the progression of CRC and oxaliplatin-resistance are largely unknown. Methods Oxaliplatin-resistant CRC and normal intestinal FHC cells were transfected with a miR-128-3p expression lentivirus. After transfection, FHC-derived exosomes were isolated and co-cultured with CRC cells. miR-128-3p expression in resistant CRC cells, FHC cells, and exosomes was quantified by quantitative real-time PCR (RT-qPCR). The mRNA and protein levels of miR-128-3p target genes in resistant CRC cells were quantified by RT-qPCR and western blot, respectively. The effects of miR-128-3p on CRC cell viability, apoptosis, EMT, motility and drug efflux were evaluated by CCK8, flow cytometry, Transwell and wound healing assays, immunofluorescence, and atomic absorption spectrophotometry. Xenograft models were used to determine whether miR-128-3p loaded exosomes can re-sensitize CRC cells to oxaliplatin in vivo. Results In our established stable oxaliplatin-resistant CRC cell lines, in vitro and vivo studies revealed miR-128-3p suppressed EMT and increased intracellular oxaliplatin accumulation. Importantly, our results indicated that lower miR-128-3p expression was associated with poor oxaliplatin response in advanced human CRC patients. Moreover, data showed that miR-128-3p-transfected FHC cells effectively packaged miR-128-3p into secreted exosomes and mediated miR-128-3p delivery to oxaliplatin-resistant cells, improving oxaliplatin response in CRC cells both in vitro and in vivo. In addition, miR-128-3p overexpression up-regulated E-cadherin levels and inhibited oxaliplatin-induced EMT by suppressing Bmi1 expression in resistant cells. Meanwhile, it also decreased oxaliplatin efflux through suppressed expression of the drug transporter MRP5. Conclusion Our results demonstrate that miR-128-3p delivery via exosomes represents a novel strategy enhancing chemosensitivity in CRC through negative regulation of Bmi1 and MRP5. Moreover, miR-128-3p may be a promising diagnostic and prognostic marker for oxaliplatin-based chemotherapy.

The addition of aluminum (Al) to the fuel is an effective way to increase the regression rate of hybrid rocket motors (HRMs). Due to its high regression rate, the impact of the regression of combustion surface on the performance of HRMs cannot be ignored. Therefore, it is significant to establish a dynamic numerical simulation model to predict the performance of HRMs. In this study, the dynamic simulation model was established based on dynamic mesh technology and was verified by a firing test. The results show that the simulation results agree well with the experimental results, and the errors of the average thrust and combustion chamber pressure are 3.4% and 1.4%, respectively. The dynamic simulation shows that with the regression of the combustion surface, the vortex of the pre-combustion chamber is divided into two vortices. The vortex near the front of the grain will increase the regression rate downstream. The results show that the addition of Al can obviously improve the regression rate of HRMs. The fuel containing 58% Al can improve the regression rate by 88.8% compared with the fuel with pure hydroxyl-terminated polybutadiene (HTPB). Moreover, due to the higher combustion temperature and the scouring of metal particles, the ablation rate of the nozzle with carbon ceramic materials reaches 0.16 mm/s. This investigation provides a valuable reference for HRMs design and simulation.

A novel fuel grain configuration comprising two star-segmented grains is proposed. The effect of the rotation, mid-chamber length, and segmented position on the fuel regression rate and the combustion efficiency in hybrid rocket motors with star-segmented grains is investigated in this paper. To this end, 90% hydrogen peroxide (H2O2) and hydroxyl-terminated polybutadiene (HTPB) are selected as the propellant combination in this research. Three-dimensional numerical simulations of the star-segmented grain configuration are conducted. A firing test of a lab-scale hybrid rocket motor was conducted to verify the accuracy of the numerical model, and the errors between simulation data and experimental results are no more than 4.5%. The case without segmented grain configuration is regarded as the base case. The simulation results demonstrate that the combustion flow field structure of the motor could be ameliorated by the segmented rotation grain configuration. Compared with the base case, the rotation of aft-section grain has little effect on the regression rate in the fore-section grain, while the average regression rate in aft-section grain increases, with a maximum increase of 25.04%. The combustion efficiency of the motor with the segmented rotation grain configuration is higher than the base case. Compared with the base case, the combustion efficiency of segmented rotation grain case with mid-chamber length 40 mm and segmented position of 1/2 is raised by 4.06%. The average fuel regression rate and the combustion efficiency of hybrid rocket motors with segmented rotation grains are higher than those in the base case during the entire period of operation, and the combustion efficiency is increased by 1.40–4.21% during the motor operation. The research findings of this paper can provide valuable guidance for the performance improvement of hybrid rocket motors with star grain.

Polycystic ovary syndrome (PCOS) is an endocrinopathy with complex pathophysiology that is a common cause of anovulatory infertility in women. Although the disruption of circadian rhythms is indicated in PCOS, the role of the clock in the etiology of these pathologies has yet to be appreciated. The nuclear receptors REV-ERBα and REV-ERBβ are core modulators of the circadian clock and participate in the regulation of a diverse set of biological functions. However, in PCOS, the expression of REV-ERBs and their effects remain unclear. Here, we demonstrate that the levels of REV-ERBα and REV-ERBβ expression were lower in the granulosa cells of PCOS patients than in control subjects. In vitro, we found that the overexpression of REV-ERBα and REV-ERBβ, and their agonist SR9009, promoted the expression of mitochondrial biosynthesis genes PGC-1α, NRF1, and TFAM and inhibited autophagy in KGN cells. Our results also indicate that REV-ERBα and REV-ERBβ can inhibit apoptosis in granulosa cells and promote proliferation. Importantly, the REV-ERB agonist SR9009 ameliorates abnormal follicular development by promoting mitochondrial biosynthesis and inhibiting autophagy in a mouse PCOS model. This allows us to speculate that SR9009 has potential as a therapeutic agent for the treatment of PCOS.

Radiation enteritis is the most common and serious complication of abdominal or pelvic radiation therapy. Mesenchymal stem cells (MSCs), as well as cell protection agents, inhibit apoptosis and promote the proliferation of injured tissues. 3 human umbilical cords MSCs (UCMSCs) were injected into the tail vein or peritoneal cavity of a rat model of radiation enteritis. The temporary protective effect was assessed by identification of donor cells, detection of cellular immune parameters and inflammatory cytokine levels, quantitation of jejunum mucosal preservation and examination of the rat remaining life. Only the rats in the intraperitoneal injection group exhibited a few positive donor cells 7 days after transplantation. CD 4 + /CD 8 + T cells, a cellular immune parameter, decreased in the abdominal exudate of intraperitoneal injection group, compared with the model-only control and tail vein groups (both P < .05). Both serum and abdominal exudate TNF-α and IL-6 levels in the intraperitoneally injected rats rapidly decreased and were significantly different from those in the model-only control and tail vein injection groups (all P < .05). Mucosal surface area and survival time increased in the intraperitoneal injection group compared with the vehicle and tail vein injection groups (all P = .000). Therefore, the administration of UCMSCs with intraperitoneal injection approach postponed death in a rat model of radiation enteritis, which was associated with reduced serum levels of proinflammatory cytokines (TNF-α, IL-6). However, UCMSCs injected via the tail vein triggered an intense cellular immune response in the serum that adversely affects their survival. This treatment failed to suppress circulating serum and abdominal exudate levels of TNF-α and IL-6 and could not provide a therapeutic benefit for prolonging life against acute radiation enteritis.

Absent in melanoma 2 (AIM2) as an immune regulator for the regulation of tumor-associated macrophages (TAMs) function is unclear in tumor development. Here, the AIM2 function was investigated in TAMs-mediated malignant behaviors of renal carcinoma. The correlation analysis result showed that the AIM2 expression in TAMs was negatively correlated with the percentages of M2-like polarization phenotype in human or murine renal cancer specimens. By the cocultured assay with bone marrow-derived macrophages (BMDMs) and Renca cells, overexpression of AIM2 in macrophages enhanced the inflammasome activation and reversed the phenotype from M2 to M1. Compared with BMDMs-Ctrl cocultured group, BMDMs-AIM2 cocultured group showed reduced tumor cell proliferation and migration. The blockade of inflammasome activation by the inhibitor Ac-YVAD-CMK abrogated AIM2-mediated M1 polarization and the inhibition of tumor cell growth. To evaluate the therapeutic efficacy of AIM2-mediated M1 macrophages in vivo, BMDMs-AIM2 were intravenously injected into subcutaneous Renca-tumor mice. The results showed that the infiltration of M1 TAMs was increased and tumor growth was suppressed in BMDMs-AIM2-treated mice when compared with BMDMs-Ctrl-treat mice. Accordingly, the blockade of inflammasome activation reduced the anti-tumor activities of BMDMs-AIM2. Moreover, the lung metastases of renal carcinoma were suppressed by the administration of BMDMs-AIM2 accompanied with the reduced tumor foci. These results demonstrated that AIM2 enhanced TAMs polarization switch from anti-inflammatory M2 phenotypy to pro-inflammatory M1 through inflammasome signaling activation, thus exerting therapeutic intervention in renal carcinoma models. Our results provide a possible molecular mechanism for the modulation of TAMs polarization in tumor microenvironment and open a new potential therapeutic approach for renal cancer.

Systematic studies are quite rare on the gas-bearing property and its controlling factors of the shallow Longmaxi shale outside the Sichuan Basin. In a previous study, the gas in place contents of a suit of Longmaxi shale samples with a depth range of 362–394 m from the well XK2, which was drilled in the Xishui area, Guizhou, southern China, were reported. In the present study, the pore structure parameters and irreducible water occurrence characteristics of those samples, and their influences on the gas-bearing property were further investigated. The results show that, compared to the dry sample, the non-micropore specific surface areas and micropore volumes of the moist sample are significantly reduced by an average value of 61 and 30%, respectively, and that the water averagely occupies 82 and 41% of the inorganic and organic non-micropore specific surface areas, respectively, and 44 and 18% of the inorganic and organic micropore volumes, respectively. The shallow shale reservoir is dominated by adsorbed gas. It accounts for 66–93% of the total gas. The water significantly decreases the adsorption capacity of the inorganic matte (mainly clay minerals) pores, but has a limited influence on that of the organic matter pores. The adsorbed gas occurs mostly in the organic matter nanopores, and even if the shales were highly saturated with the water, they can still store a certain amount of the adsorbed gas. These results are to provide some guides for the evaluation and exploration of the shallow Longmaxi shale located in the strongly tectonic transformation areas of southern China.

To rapidly detect whether apples are infected by fungi, a portable electronic nose was used in this study to collect the gas information from apples, and the collected information was processed by smoothing filtering, data dimensionality reduction, and outlier removal. Following this, we utilized K-nearest neighbors (KNN), random forest (RF), support vector machine (SVM), a convolutional neural network (CNN), a back-propagation neural network (BPNN), a particle swarm optimization–back-propagation neural network (PSO-BPNN), a gray wolf optimization–backward propagation neural network (GWO-BPNN), and a sparrow search algorithm–backward propagation neural network (SSA-BPNN) model to discriminate apple samples, and adopted the 10-fold cross-validation method to evaluate the performance of each model. The results show that SSA can effectively optimize the performance of the BPNN, such that the recognition accuracy of the optimized SSA-BPNN model reaches 98.40%. This study provides an important reference value for the application of an electronic nose in the non-destructive and rapid detection of fungal infection in apples.

An understanding of physiological damage and population development caused by uncomfortable temperature plays an important role in pest control. In order to clarify the adaptability of different temperatures and physiological response mechanism of B. dorsalis, we focused on the adaptation ability of this pest to environmental stress from physiological and ecological viewpoints. In this study, we explored the relationship between population parameters and glucose, glycogen, trehalose, and trehalose-6-phosphate synthase responses to high and low temperatures. Compared with the control group, temperature stress delayed the development duration of all stages, and the survival rates and longevity decreased gradually as temperature decreased to 0 °C and increased to 36 °C. Furthermore, with low temperature decrease from 10 °C to 0 °C, the average fecundity per female increased at 10 °C but decreased later. Reproduction of the species was negatively affected during high-temperature stresses, reaching the lowest value at 36 °C. In addition to significantly affecting biological characteristics, temperature stress influenced physiological changes of B. dorsalis in cold and heat tolerance. When temperature deviated significantly from the norm, the levels of substances associated with temperature resistance were altered: glucose, trehalose, and TPS levels increased, but glycogen levels decreased. These results suggest that temperature stresses exert a detrimental effect on the populations’ survival, but the metabolism of trehalose and glycogen may enhance the pest’s temperature resistance.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12943-019-0981-7.

Baikouquan oil field is composed of multiple interbedded, thin, low-permeability layers, which are required to vertically fracture multiple layers and to create complex fractures for economic development. However, conventional fracture technologies create a single, simple fracture, having poor feasibility for this field. Therefore, we conducted research on fracturing technology by spontaneously selecting geologic sweet spots based on diversion. This technology can vertically fracture the thin layers one by one and horizontally divert the fracture to non-depleted areas. Firstly, a triaxial diverted fracturing experiment approach was setup, and then diverted fracturing experiments were carried out to verify the feasibility of diverted fracturing and to study the fracture geometry and the law of diversion. Next, experiments were carried out to evaluate the performance of the diversion agents. The valuated properties comprise the diversion pressure, stability time, and degradation based on which to optimize the selection of the diversion agents. Finally, the fracturing technology was applied to well b21004 of Baikouquan oil field, and post-frac performance was evaluated. The experimental results show that multiple and complex fractures are realized through temporary plugging. Diversion performance evaluation tests show that a 4 wt% concentration of 1–5 mm granules + 20/60 mesh powder and a 3 wt% concentration of 1–7 mm granules + 20/60 mesh powder + fiber can hold up enough pressure to force the fracture to divert. The field treating pressure curve shows that there is a 3–10 MPa pressure increase when there are pump diversion agents, which is a clear sign of fracture diversion. Plugging the fracture mouth gives a faster and a higher incremental pressure. Before this fracturing, the well had almost stopped oil production. After the stimulation, the initial oil production rate became 20 + t/d, which shows the effectiveness of this fracturing technology for Baikouquan oil field.

In this paper, we focus on the existence of positive solutions for a boundary value problem of the changing-sign differential equation on time scales. By constructing a translation transformation and combining with the properties of the solution of the nonhomogeneous boundary value problem, we transfer the changing-sign problem to a positone problem, then by means of the known fixed-point theorem, several sufficient conditions for the existence of positive solutions are established for the case in which the nonlinear term of the equation may change sign.

Summary: As one of the most spectacular energy release events in the solar system, solar flares are generally powered by magnetic reconnection in the solar corona. As a result of the re-arrangement of magnetic field topology after the reconnection process, a series of new loop-like magnetic structures are often formed and are known as flare loops. A hot diffuse region, consisting of around 5–10 MK plasma, is also observed above the loops and is called a supra-arcade fan. Often, dark, tadpole-like structures are seen to descend through the bright supra-arcade fans. It remains unclear what role these so-called supra-arcade downflows (SADs) play in heating the flaring coronal plasma. Here we show a unique flare observation, where many SADs collide with the flare loops and strongly heat the loops to a temperature of 10–20 MK. Several of these interactions generate clear signatures of quasi-periodic enhancement in the full-Sun-integrated soft X-ray emission, providing an alternative interpretation for quasi-periodic pulsations that are commonly observed during solar and stellar flares.

In past studies, researchers find that endpoint degree, H-index, and coreness can quantify the influence of endpoints in link prediction, especially the synthetical endpoint degree and H-index improve prediction performances compared with the traditional link prediction models. However, neither endpoint degree nor H-index can describe the aggregation degree of neighbors, which results in inaccurate expression of the endpoint influence intensity. Through abundant investigations, we find that researchers ignore the importance of coreness for the influence of endpoints. Meanwhile, we also find that the synthetical endpoint degree and coreness can not only describe the maximal connected subgraph of endpoints accurately but also express the endpoint influence intensity. In this paper, we propose the DCHI model by synthesizing endpoint degree and coreness and the HCHI model by synthesizing H-index and coreness on SRW-based models, respectively. Extensive simulations on twelve real benchmark datasets show that, in most cases, DCHI shows better prediction performances in link prediction than HCHI and other traditional models.

In this paper, the effects of different grain shapes of a hybrid rocket motor (HRM) and different payload mass/orbit heights on the design of small launch vehicles (SLVs) are systematically discussed. An integrated overall design model for the hybrid rocket motor-powered small launch vehicle (HPSLV) is established, and two groups of three-stage SLVs capable of sending small payloads to the low earth orbit (LEO) are designed and optimized. In the first group, the SLVs with different grain shapes and different numbers of chambers in HRMs at the 1st and the 2nd stages are optimized and analyzed. In the second group, the SLVs capable of sending different payload mass to different orbit heights are optimized and analyzed. Pareto graphs of the design results show that the design of HRM at the 1st stage has the greatest impact on the take-off mass, total velocity increment, and maximum axial overload of the SLV. Self-organizing maps show that the take-off mass, maximum diameter, overall length, and velocity increment of the SLVs have the same variation tendency. For the 1-chamber HRM at the 1st stage, the wheel-shaped grain is better than circle-shaped and star-shaped grains in terms of reducing the total mass and length of the SLV, and the 4-chamber parallel HRM has more advantages over all 1-chamber designs for the same reason. The theoretical velocity increments are calculated by the Tsiolkovsky formula, and the actual velocity increments are obtained based on the trajectory simulation data. The results indicate that the HPSLV has a regular distribution in terms of the ratio of theoretical (actual) velocity increments at three different stages, and the estimated distribution ratio is around 1 : 1.55 : 1.69 (1 : 1.9 : 2.39), which can provide some reference for future development of HPSLV.

In recent years, hemorrhagic fever with renal syndrome (HFRS) incidence has been becoming a severe public health problem again due to its significant increase in Shaanxi Province, China. Baoji, located in the Guanzhong Plain in the central part of Shaanxi Province, has been severely affected by HFRS since its first emergence in 1955. To better understand the epidemiology of orthohantaviruses infection in humans and the causative agents carried by the rodents, the long-term incidence patterns were analyzed and a molecular epidemiological investigation of orthohantaviruses infection in humans and rodents was performed. During 1984-2019, 13,042 HFRS cases were registered in Baoji, including 275 death cases. Except the first high prevalence of HFRS in 1988-1993, another two epidemic peaks were observed in 1998-2003 and 2012, respectively, although vaccination project was started since 1996. During the same period, HFRS cases in Baoji mainly were recorded in winter suggesting they may be caused by Hantaan orthohantavirus (HTNV), while a small peak of HFRS was also found in summer with unknown reason. Nucleotide identity and phylogenetic analyses demonstrated that a novel clade of HTNV sequences recovered from HFRS cases were closely related to those from rodents, including species close contact with humans, suggesting a direct viral transmission from rodents to humans and the important role in the HTNV transmission the nontraditional rodent hosts may play. Moreover, two distant related Dabieshan orthohantavirus (DBSV) lineages were also identified in Niviventer niviventer in this area demonstrating its considerable genetic diversity. Our data indicated that continual spillover of HTNV from rodents to humans, contributing to the high prevalence of HFRS in humans in Baoji.

This study aimed to investigate the prognostic value and molecular mechanism of DDX39 and its effector SNAIL in melanoma. First, overexpression of DDX39 in melanoma, which was identified by database analysis, was further validated in patient tissues. Cell growth, cell cycle, cell migration, and cell invasion assays were then performed to evaluate the effects of downregulated DDX39 on the melanoma cell proliferation and aggressiveness. The same approaches were also used to reveal the cooperation of the transcription factor SNAIL with DDX39 to promote the aggressiveness of melanoma cells. We found that the expression of DDX39 was significantly upregulated in melanoma tissue compared to pigmented nevus tissue, and it was positively correlated with the clinical stage defined by the American Joint Committee on Cancer (AJCC) and the prognosis. Downregulation of DDX39 in melanoma cells was found to significantly inhibit cell proliferation, increase G2/M cell cycle arrest, enhance caspase-mediated cell apoptosis, and suppress cell invasion and migration. In addition, we demonstrated that the overexpression of SNAIL could restore the cell growth and aggressiveness impaired by DDX39 RNA interference. Immunohistochemical staining also showed a positive correlation between DDX39 overexpression and SNAIL overexpression in melanoma tissues, suggesting that SNAIL is one of the effectors activated by DDX39. In summary, the overexpression of DDX39 and SNAIL was positively related to the poor prognosis of melanoma patients and the increased aggressiveness of melanoma cells. Our study provides valuable evidence regarding the prognostic value of DDX39 and SNAIL as well as their potential as novel therapeutic targets for treating melanoma patients.

Mitochondria as the cellular energy powerhouses provide a common site for multiple metabolic reactions in order to cover energy and biomolecule demands, thus integrating the diverse metabolic pathways to endow cells with metabolic adaptation. Mitochondrial plasticity is normally regulated by mitochondrial dynamics, mitochondrial metabolism and mitochondrial biogenesis. Given that tumor cells and T cells share the metabolic similarities of survival, proliferation, expansion as well as effector function, manipulation of mitochondrial plasticity would change the metabolic competition between “foe” and “friend” during tumor malignant progression. On the one hand, for “foe” tumor cells, mitochondrial plasticity provides the enhancement of tumor metastasis and the development of resistance to‘ diverse antitumor drugs. On the other hand, for “friend” T cells, mitochondrial plasticity promotes the generation of long-term memory T (TM) cells and alleviates the exhaustion of tumor-infiltrating lymphocytes (TILs). Therefore, downregulation of mitochondrial plasticity of tumor cells through engineering tumor-targeting nanoparticles may effectively potentiate metabolic vulnerability and re-sensitize tumor to relevant therapeutic treatment. On the contrary, upregulation of mitochondrial plasticity of T cells through optimizing adoptive cellular immunotherapy (ACI) or chimeric antigen receptor (CAR)-T cell therapy would provide T cells with the robust metabolic fitness and the persistent immune function, thus blocking tumor metastasis and reoccurrence.

Objective Interventions for hyperinsulinemia (HINS), an early indicator of type 2 diabetes mellitus (T2DM), can significantly reduce the T2DM risk. This study aims to determine how dipeptidyl peptidase-4 (DPP-4) inhibition prevents HINS progression to T2DM through ameliorating hepatic steatosis. Methods KKay mice were used as a HINS model and they underwent exercise or received a DPP-4 inhibitor, MK0626. Hepatic steatosis was examined and liver diacylglycerol levels were determined. Human hepatic cells (LO2) were treated with MK0626 or transfected with DPP-4 siRNA. Protein kinase C ε isoform (PKCε) and DPP-4 expression and insulin receptor substrate 1 (IRS-1) phosphorylation were assessed using immunohistochemistry and western blot. Results KKay mice developed HINS spontaneously at 7 weeks of age. Similar to exercise, MK0626 ameliorated hepatic steatosis and reduced the liver triglyceride and diacylglycerol content. Both exercise and MK0626 suppressed diacylglycerol-induced PKCε expression and restored insulin signaling, which was shown by tyrosine phosphorylation of IRS-1, in the livers of KKay mice. Additionally, silencing DPP-4 or MK0626 treatment decreased PKCε expression in LO2 cells. Conclusions Our data demonstrate that DPP-4 inhibition resembles exercise and effectively delays T2DM onset by suppressing hepatic PKCε expression in the HINS mouse model.

Plants trigger immune responses upon recognition of fungal cell wall chitin, followed by the release of various antimicrobials, including chitinase enzymes that hydrolyze chitin. In turn, many fungal pathogens secrete LysM effectors that prevent chitin recognition by the host through scavenging of chitin oligomers. We previously showed that intrachain LysM dimerization of the Cladosporium fulvum effector Ecp6 confers an ultrahigh-affinity binding groove that competitively sequesters chitin oligomers from host immune receptors. Additionally, particular LysM effectors are found to protect fungal hyphae against chitinase hydrolysis during host colonization. However, the molecular basis for the protection of fungal cell walls against hydrolysis remained unclear. Here, we determined a crystal structure of the single LysM domain-containing effector Mg1LysM of the wheat pathogen Zymoseptoria tritici and reveal that Mg1LysM is involved in the formation of two kinds of dimers; a chitin-dependent dimer as well as a chitin-independent homodimer. In this manner, Mg1LysM gains the capacity to form a supramolecular structure by chitin-induced oligomerization of chitin-independent Mg1LysM homodimers, a property that confers protection to fungal cell walls against host chitinases.

Objective: This study aimed to identify additional characteristics and features of coronavirus disease (COVID-19) by assessing the clinical courses among COVID-19 patients in a region outside Hubei province.Methods: We analyzed retrospective data regarding general characteristics, epidemiologic history, underlying chronic diseases, clinical symptoms and complications, chest computed tomography findings, biochemical monitoring, disease severity, treatments, and outcomes among 37 adult patients with COVID-19. According to the duration from symptom onset to release from quarantine, the patients were divided into the ≤20 and >20-day groups, and the similarities and differences between them were compared.Results: Among the 37 patients, five had mild disease, 30 had moderate disease, one had severe disease, and one was critically ill. All of the patients were released from quarantine, and no mortality was observed. The average duration from symptom onset to release from quarantine was 20.2 ± 6.6 days. The average duration from symptom onset to hospitalization was 4.1 ± 3.7 days, and the patients were hospitalized for an average of 16.1 ± 6.2 days. The average age was 44.3 ± 1.67 years, and 78.4% of cases were caused by exposure to a patient with confirmed disease or the workplace of a patient with confirmed disease. The main symptoms were cough (67.6%), fever (62.2%), shortness of breath (32.4%), fatigue (24.3%), sore throat (21.6%), vomiting, and diarrhea (21.6%). White blood cell count was decreased in 27.0% of patients, and lymphocyte count was decreased in 62.2% of the patients, among whom 43.5% patients had counts of ≤0.6 × 109/L. On admission, 86.5% of patients showed pneumonia in chest CT scans, including some asymptomatic patients, while 68.8% of patients showed bilateral infiltration. In the >20-day group, the average age was 49.9 ± 1.38 years, and the average duration from symptom onset to hospitalization was 5.5 ± 3.9 days. Compared with the ≤20-day group, patients in the >20-day group were older and the duration was longer (P < 0.05). All of the seven asymptomatic patients belonged to the ≤20-day group. When the 37 patients were released from quarantine, the white blood cell count of 16.2% of the patients was 0.05).Conclusion: The majority of COVID-19 cases in the study area were mild and moderate, with good clinical outcomes. There were some special characteristics in the clinical course. The reasons for differences in the duration from symptom onset to release from quarantine were complex. There was no significant change in the number of granulocytes at the time of release from quarantine compared to that at the time of admission.

This paper reports the clinical characteristics, diagnosis, and treatment of the first critical COVID-19 patient in Liaocheng City, who was admitted to the intensive care unit isolation ward of Liaocheng People's Hospital on February 11, 2020. On admission, the patient had difficulty breathing, the oxygenation index was 135 mmHg, and the blood lactate was 5.6 mmol/L. After comprehensive treatment including high-flow nasal cannula oxygen therapy, plasma exchange, antiviral and anti-infection therapies, immune regulation, liquid volume management, glucocorticoid, enteral nutrition support, analgesia and sedation, blood glucose control, anticoagulation and thrombus prevention, and electrolyte balance maintenance, the patient was finally cured, and discharged. The purpose of this case report is to provide a reference for the clinical diagnosis and treatment of critical COVID-19 patients.