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In this article, we calculate the value-at-risk (VaR) for large portfolios in intensity models, where the idiosyncratic and systematic risk exposures as well as the impact of past default losses are subsumed into the intensity processes. The adopted method is based on the theory of saddlepoint approximation for continuous-time Markov processes whose transition densities and distribution functions can be approximated in closed forms. A simple example with theoretical and numerical results is presented in the end. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is a very serious diabetes complication. Changes in the O-linked N-acetylglucosamine (O-GlcNAc) modification are associated with many diseases. However, its role in DR is not fully understood. In this research, we explored the effect of O-GlcNAc modification regulation by activating AMP-activated protein kinase (AMPK) in DR, providing some evidence for clinical DR treatment in the future. Bioinformatics was used to make predictions from the database, which were validated using the serum samples of diabetic patients. As an in vivo model, diabetic mice were induced using streptozotocin (STZ) injection with/without an AMPK agonist (metformin) or an AMPK inhibitor (compound C) treatment. Electroretinogram (ERG) and H&E staining were used to evaluate the retinal functional and morphological changes. In vitro, 661 w cells were exposed to high-glucose conditions, with or without metformin treatment. Apoptosis was evaluated using TUNEL staining. The protein expression was detected using Western blot and immunofluorescence staining. The angiogenesis ability was detected using a tube formation assay. The levels of O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) in the serum changed in the DR patients in the clinic. In the diabetic mice, the ERG wave amplitude and retinal thickness decreased. In vitro, the apoptotic cell percentage and Bax expression were increased, and Bcl2 expression was decreased in the 661 w cells under high-glucose conditions. The O-GlcNAc modification was increased in DR. In addition, the expression of GFAT/TXNIP O-GlcNAc was also increased in the 661 w cells after the high-glucose treatment. Additionally, the Co-immunoprecipitation(CO-IP) results show that TXNIP interacted with the O-GlcNAc modification. However, AMPK activation ameliorated this effect. We also found that silencing the AMPKα1 subunit reversed this process. In addition, the conditioned medium of the 661 w cells may have affected the tube formation in vitro. Taken together, O-GlcNAc modification was increased in DR with photoreceptor cell degeneration and neovascularization; however, it was reversed after activating AMPK. The underlying mechanism is linked to the GFAT/TXNIP-O-GlcNAc modification signaling axis. Therefore, the AMPKα1 subunit plays a vital role in the process. [ABSTRACT FROM AUTHOR]

Finding reliable and easy-to-obtain predictors of severe infectious complications after shock wave lithotripsy (SWL) is a major clinical need, particular in symptom-free hydronephrosis. Therefore, we aim to prospectively investigate the predictive value of Hounsfield units (HU) in renal pelvis urine for the risk of severe infectious complications in patients with ureteral stones and symptom-free hydronephrosis after SWL. This multi-center prospective study was conducted from June 2020 to December 2023. The HU of renal pelvis urine was measured by non-enhanced computed tomography. The severe infectious complications included systemic inflammatory response syndrome, sepsis, and septic shock. Binary logistic regression models assessed the odds ratios (ORs) and 95% confidence intervals (CIs). Finally, 1,436 patients with ureteral stones were enrolled in this study. 8.9% (128/1,436) of patients experienced severe infectious complications after SWL treatment. After adjusting confounding variables, compared with the patients in the lowest renal pelvis urine density quartile, the OR (95% CI) for the highest quartile was 32.36 (13.32, 78.60). There was a positive linear association between the HU value of renal pelvis urine and the risk of severe infectious complications after SWL (P for trend < 0.001). Furthermore, this association was also observed stratified by age, gender, BMI, stone size, stone location and hydronephrosis grade (all P for interaction > 0.05). Additionally, the nonlinear association employed by restricted cubic splines is not statistically significant (nonlinear P = 0.256). The AUROC and 95%CI of renal pelvis urine density were 0.895 (0.862 to 0.927, P value < 0.001). The cut-off value was 12.0 HU with 78.59% sensitivity and 85.94% specificity. This multi-center prospective study demonstrated a positive linear association between HU in renal pelvis urine and the risk of severe infectious complications in patients with ureteral stones and symptom-free hydronephrosis after SWL, regardless of age, gender, BMI, stone size, stone location, and hydronephrosis grade. These findings might be helpful in the SWL treatment decision-making process. [ABSTRACT FROM AUTHOR]

Simultaneous transmit and receive wireless communications have been highlighted for their potential to double the spectral efficiency. However, it is necessary to mitigate self-interference (SI). Considering both the SI channel and remote transmission (RT) channel need to be estimated before equalizing the received signal, we propose two adaptive algorithms for linear and nonlinear self-interference cancellation (SIC), based on a multi-layered joint channel estimator structure. The proposed algorithms estimate the RT channel while performing SIC, and the multi-layered structure ensures improved performance across various interference-to-signal ratios. The M-estimate function enhances the robustness of the algorithm, allowing it to converge even when affected by impulsive noise. For nonlinear SIC, this paper introduces an adaptive algorithm based on generalized Hammerstein polynomial basis functions. The simulation results indicate that this approach achieves a better convergence speed and normalized mean squared difference compared to existing SIC methods, leading to a lower system bit error rate. [ABSTRACT FROM AUTHOR]

In this paper, we employ correlated skew Brownian motions to describe the dynamics of the two assets underlying the spread option. In the pricing model, the two underlying assets are exposed to exogenous risks captured by the same Brownian motion, and their endogenous risks are also assumed to be correlated with each other. We obtain an approximate pricing formula of spread options and calibrate model parameters to real data. In addition, we compare the results obtained from the approximate formula with those derived from the exact closed-form formula and from the Monte Carlo method. Finally, we analyze the impact of the skewness parameter on option prices after checking the accuracy of the approximations numerically. [ABSTRACT FROM AUTHOR]

Due to factors such as a small amount of fertilizer application during rice topdressing and slow machine speed, the ordinary fertilizer discharge device fails to distribute the fertilizer uniformly and accurately as required, making it difficult to meet the needs of precise rice topdressing. This research focuses on the development of an offset spiral tooth fertilizer discharge device suitable for rice topdressing. The study analyzes the amount of fertilizer discharged in one cycle, the fertilizer force, and the motion of the fertilizer particles. In order to enhance the uniformity of the fertilizer discharge device at a low speed and small volume, the discrete element method is employed to conduct experimental research on the key structural parameters that affect the one-cycle amount of discharged fertilizer and the dynamics of the fertilizer discharge device. Through single-factor tests, it was found that the angle, height, number of spiral teeth, and diameter of the fertilizer discharge wheel are closely associated with the fertilizer discharge performance. To further investigate the impact of these four parameters on the fertilizer discharge performance, a regression combination test of the four factors is conducted based on the range optimized by the single-factor tests. A multi-objective mathematical model, considering the key parameters of fertilizer uniformity coefficient, one-cycle amount of fertilizer, and fertilizer discharge torque, is established at three speeds: 20, 55, and 90 rpm. The response surface method is utilized to analyze the influence of the interaction factors on the fertilizer discharge performance. The optimal combination of the key structural parameters was determined as follows: spiral tooth angle of 35.42°, tooth height of 9.02 mm, discharge wheel diameter of 57.43 mm, and tooth amount of 9.37. The bench test results of the device, using the optimal parameter combination and a fertilizer discharge speed of 0–90 rpm, were obtained for four commonly used rice fertilizers. The maximum variation coefficient of fertilizer discharge was found to be 10.42%. The one-cycle amount of fertilizer discharge was measured to be 19.82 ± 0.72 (A Kang), 17.20 ± 0.69 (Ba Tian), 20.34 ± 0.54 (Yaran), and 14.51 ± 0.44 (granular urea). The fertilizer discharge torque remained stable. These results indicate that the achieved optimization meets the precise fertilizer application requirements and can provide technical support for precise topdressing operations. [ABSTRACT FROM AUTHOR]

Widespread interest has been drawn to the use of solid waste fillers as a partial replacement for natural fillers in high-performance asphalt mixtures in recent years. However, variations in the material properties of solid waste fillers remain a problem for the recycling method. To address this issue, the limestone powder in asphalt mixtures was replaced with three solid waste fillers, including steel slag powder, tailings powder and calcium carbide slag powder in this study. The chemical composition of the fillers was first characterized to assess the homogeneity of the material. Then, a dense-graded asphalt mixture (AC) and a stone matrix asphalt (SMA) mixture were designed, produced and characterized for wet stability. The results show that the asphalt mixtures with solid waste fillers were superior to limestone powder (LP) asphalt mixtures in terms of resistance to water damage, and the steel slag powder showed the best improvement in moisture stability of the asphalt mixtures. The optimum substitution of solid waste filler for limestone filler was 25%. With the addition of anti-stripping agents, the moisture stability of the asphalt mixture with limestone filler was also greatly enhanced. On the contrary, a marginal enhancement was observed in the moisture stability of asphalt mixtures using solid waste fillers. Solid waste fillers can be used in asphalt mixtures and have a similar function as that of anti-stripping agents. In summary, the use of solid waste fillers to replace mineral fillers in asphalt mixtures is a reliable, value-added recycling option. [ABSTRACT FROM AUTHOR]

In this study, the optimal forming parameters for printing flexible circuits using aerosol jet printing technology are explored through numerical simulation and experiments. The printhead during the deposition process is numerically simulated. By employing the controlled variable method, the process parameters such as gas flow rate, working distance, nozzle diameter, and printing speed are selected to investigate their effects on the morphology of the printed lines. Accordingly, single-factor experiments are designed to validate the printing of flexible circuits on both planar and curved substrates. Laser micro-sintering is utilized to improve the conductivity of the printed lines and ultimately fabricate flexible strain sensors. Under the sheath gas flow rate of 400 sccm, carrier gas flow rate of 100 sccm, working distance of 3 mm, nozzle diameter of 500 μm, and printing speed of 10 mm/s, the optimal morphology of the printed lines is achieved with low linewidth characteristics. The variations in the focal ratio, working distance, nozzle diameter, and printing speed significantly affect the minimum feature line width and morphology of the printed lines. [ABSTRACT FROM AUTHOR]

40CrNiMoA steel was nitrided by arc plasma-assisted nitriding (PAN) process at 430 °C, 1 Pa for 3 h with different N2/Ar ratios. Their structures, micrographs, microhardness profiles and tribological properties were investigated by X-ray diffraction (XRD), optical microscope, SEM, Vickers microhardness tester and pin-on-disk tribometer, respectively. All of the nitrided layers were primarily consisted of the γ′-Fe4N and ε-Fe3N. The thickness of compound layers increased with the N2/Ar ratio increasing. The maximum thickness of the compound layer was about 6 μm after nitriding, while the thickness of nitrided layer reached about 230 μm. The surface microhardness and wear resistance of the steel were significantly improved. Its maximum surface microhardness enhanced as 3 times (approx.) as that of the substrate. The wear mechanism changed from adhesive wear to abrasive wear. In addition, the nitrided sample treated at N2/Ar ratio of 75%:25% had the optimum abrasion resistance and lowest wear rate. [ABSTRACT FROM AUTHOR]

More and more evidence suggests that puerarin, a potential remedy for gut inflammation, may have an ameliorative effect on sleep disturbances. However, the relationship between puerarin and sleep disruption has not been extensively researched. This study aims to explore the role and mechanisms of puerarin in improving sleep disorders. We established a light-induced sleep disorder model in mice and assessed the effects of puerarin on cognitive behavior using open field and water maze tests. Pathological detection demonstrated that sleep disturbances resulted in observable damage to the liver, lung, and kidney. Puerarin reversed multi-organ damage and inflammation. Further, puerarin activated paneth cells, resulting in increased lysozyme and TGF-β production, and stimulating intestinal stem cell proliferation. Puerarin also effectively inhibited the expression of F4/80, iNOS, TNF-α, and IL-1β in the small intestine, while it increased Chil3, CD206, and Arg-1 levels. Moreover, puerarin treatment significantly decreased P-P65, TLR4, Bcl-xl, and cleaved caspase-3 protein levels while increasing barrier protein levels, including ZO-1, Occludin, Claudin 1 and E-cadherin suggesting a reduction in inflammation and apoptosis in the gut. Overall, puerarin diminished systemic inflammation, particularly intestinal inflammation, and enhanced intestinal barrier integrity in mice with sleep disorders. Our findings suggest a potential new therapeutic pathway for sleep disorders. [ABSTRACT FROM AUTHOR]

The widespread use of chemical herbicides has jeopardized concerns about food safety and ecological consequences. To address these issues and reduce reliance on chemical herbicides, a physical weed control device was developed for the tillering stage in paddy fields. This device features a biomimetic duckbill-like vibration chain that effectively controls weed outbreaks. The chain penetrates the soft surface soil of the paddy field under gravity and rapidly stirs the soil through vibration, leading to the detachment of the weed roots anchored in the surface layer. Simultaneously, the device avoids mechanical damage to rice seedlings rooted in deeper soil. This study aimed to investigate the effects of chain structural parameters (the number of chain rows, vibration amplitude, and length of chains) and operational parameters (vibration frequency and working velocity) on weed control efficiency and rice seedling damage. Through a central composite regression field test, the optimal device structure and operational parameters were determined. The optimization results demonstrated that a vibration amplitude of 78.8 mm, a chain length of 93.47 cm, and 3.4 rows of chains, along with a vibration frequency and working velocity ranging from 0.5 to 1.25 m/s, achieved an optimal weeding effect. Under the optimal parameter combination, field test results demonstrated that approximately 80% of the weeds in the field were effectively cleared. This indicates that the design of the biomimetic duckbill-like vibration chain weeding device exhibits a relatively superior weeding performance, offering a practical solution for the management of weeds in rice fields. [ABSTRACT FROM AUTHOR]

Plasma electrolytic oxidation (PEO) coatings were prepared using a pulsed bipolar power supply to investigate the effects of different cathodic currents on the growth mechanism of PEO coatings on 6061 aluminum alloy. The phase composition, microstructure, element distribution and content of the coatings were analyzed by X-ray diffraction (XRD), scanning electron microscope (SEM) and energy dispersive spectroscopy (EDS). It was found that the coating growth rate enhanced obviously and the discrete pores reduced significantly when the cathodic current increased. In particular, when the cathodic current density was 7.5 A/dm2, there was a soft plasma discharge phenomenon, and more α-Al2O3 crystals were generated. The distribution of Si elements reveals that the soft plasma discharge is a form of internal discharge and the coating exhibits higher hardness and compactness. It was tested using the friction tester, and the coating showed excellent wear resistance. [ABSTRACT FROM AUTHOR]

In this work, micro-arc oxidation was applied to fabricate a high voltage resistance Al2O3-based ceramic coating on the surface of aluminum alloy. The microstructure and insulating properties of the coatings were characterized by XRD, SEM and breakdown voltage testers. The growth behavior and insulation property of the oxide layer in "soft" regime conditions of micro-arc oxidation were determined. The relative contents of α-Al2O3 increased with "soft" plasma discharge time. The soft plasma discharge brought about a tendency of the micro-arc oxide coating to grow outward, further repairing the coating defects and yielding a denser coating layer with improved corrosion protection. Due to the presence of negative currents, the thickness of the whole layer increased, while the inner layer became denser and thicker as a consequence of soft sparks, favoring an increase in the density of the bulk coating layer. The breakdown voltage reached values above 1000 V after 20 min of soft plasma discharge, improving the of micro-arc oxidation coating insulation properties. The oxide layer is thus proposed as a potential candidate for insulation shielding of etching equipment. [ABSTRACT FROM AUTHOR]

Multiphoton excited luminescence is of paramount importance in the field of optical detection and biological photonics. Self-trapped exciton (STE) emission with self-absorption-free advantages provide a choice for multiphoton excited luminescence. Herein, multiphoton excited singlet/triplet mixed STE emission with a large full width at half-maximum (617 meV) and Stokes shift (1.29 eV) has been demonstrated in single-crystalline ZnO nanocrystals. Temperature dependent steady state, transient state and time-resolved electron spin resonance spectra demonstrate a mixture of singlet (63%) and triplet (37%) mixed STE emission, which contributes to a high photoluminescence quantum yield (60.5%). First-principles calculations suggest 48.34 meV energy per exciton stored by phonons in the distorted lattice of excited states, and 58 meV singlet-triplet splitting energy for the nanocrystals being consistent with the experimental measurements. The model clarifies long and controversial debates on ZnO emission in visible region, and the multiphoton excited singlet/triplet mixed STE emission is also observed.Here the author study Self-trapped exciton emission for multiphoton excited luminescence in ZnO nanoparticle which until now have not been explored. They provide a reason for the emission enhancement and apply these materials in optical imaging for a proof of concept. [ABSTRACT FROM AUTHOR]

Objectives: Current trials for HPV-associated oropharyngeal SCCs (OP-SCCs) are evaluating treatment de-escalation including use of concurrent immunotherapy with radiation therapy (I-RT). Given limited prospective data following I-RT, we aimed to examine this question utilizing the National Cancer Data Base (NCDB). Methods: The NCDB was queried for patients with HPV-associated OP-SCCs eligible for current de-escalation studies with AJCC 7th edition T1–T2/N1–N2b and T3/N0–N2b disease. Patients were stratified into I-RT, concurrent chemoradiation (C-RT), and radiation therapy alone (RT) arms. Kaplan–Meier analysis was utilized to compare overall survival (OS) between treatment arms followed by a Cox multivariate (MVA) proportional hazards model controlling for tumor and patient characteristics and propensity-score analyses with inverse probability treatment weighting (IPTW). Results: We identified 4768 patients; 313 received I-RT, 3660 patients received C-RT, and 795 received RT. Median age was 62 years (range 27–90) with a median Charlson–Deyo co-morbidity score of 0 (range: 0–3). The vast majority were cN1–N2a (88.8%) and 26.5% were cT3. On MVA, inferior 3-year and 8-year OS was noted following I-RT (81.6% and 70.5%) vs. C-RT (90.6% and 79.4%) (HR = 1.69 (95% CI: 1.29–2.21); p < 0.0001) with no significant difference vs. RT (88.1% and 75.8%) (HR = 1.07; p = 0.80). This was also maintained on IPTW-analysis (HR = 1.62 (95% CI: 1.23–2.15); p = 0.001). Conclusions: I-RT was associated with significantly poorer OS vs. C-RT with no benefit compared to RT for HPV-associated OP-SCCs. I-RT is not recommended outside of currently accruing clinical trials. [ABSTRACT FROM AUTHOR]

To realize the autonomous operation of a terraced rice sowing robot, a set of sowing robot operation path planning algorithms with universal significance for small, irregular terraced plots is proposed. According to the characteristics of terraces and the agronomic requirements of sowing seeding, the operation path mainly includes parallel operation and boundaries surrounding the operation path. The boundary pre-collision detection method is expounded, and the cyclic detection method judges the U-turn area. The Bézier curve fitting algorithm was used to smooth the boundary wrapping path. To verify the feasibility of the algorithm, four typical irregular small fields located in 666.7-hectare terraces of Sama in Hong He Prefecture, Yunnan Province, were randomly selected, and a field map was obtained through Google Earth. An existing seeding robot was used as a model, and the simulation and comparison tests were carried out with the mainstream EHNS algorithm and boundary polyline algorithm under the ROS-kinetic platform in the Cen Village Scientific Research Base of South China Agricultural University. The actual boundaries of the four fields with the same simulation test were used as the map to verify the field experiment. The simulation test results show that the area coverage of the sowing operation is greater than 93.53% and the replay rate is less than 3.46%, and the field test results show that the area coverage of the sowing operation is greater than 94.33% and the replay rate is less than 3.03%. The simulation test is in good agreement with the field test results, indicating that the algorithm has good adaptability, which meets the requirements of a sowing robot for sowing operation path planning and can provide a certain reference for the path planning of irregular field operation robots in hilly and mountainous areas. [ABSTRACT FROM AUTHOR]

Although effective, immune checkpoint blockade induces response in only a subset of cancer patients. There is an urgent need to discover new immune checkpoint targets. Recently, it was found that a class of sialic acid–binding immunoglobulin‐like lectins (Siglecs) expressed on the surface of T cells in cancer patients inhibit T cell activation through their intracellular immunosuppressive motifs by recognizing sialic acid–carrying glycans, sialoglycans. However, ligands of Siglecs remain elusive. Here, we report sialylated IgG (SIA‐IgG), a ligand to Siglec‐7, that is highly expressed in epithelial cancer cells. SIA‐IgG binds Siglec‐7 directly and inhibits TCR signals. Blocking of either SIA‐IgG or Siglec‐7 elicited potent antitumor immunity in T cells. Our study suggests that blocking of Siglec‐7/SIA‐IgG offers an opportunity to enhance immune function while simultaneously sensitizing cancer cells to immune attack. [ABSTRACT FROM AUTHOR]

In recent years, there has been an increasing focus on the application of hydrogels in tissue engineering. The integration of 3D bioprinting technology has expanded the potential applications of hydrogels. However, few commercially available hydrogels used for 3D biological printing exhibit both excellent biocompatibility and mechanical properties. Gelatin methacrylate (GelMA) has good biocompatibility and is widely used in 3D bioprinting. However, its low mechanical properties limit its use as a standalone bioink for 3D bioprinting. In this work, we designed a biomaterial ink composed of GelMA and chitin nanocrystal (ChiNC). We explored fundamental printing properties of composite bioinks, including rheological properties, porosity, equilibrium swelling rate, mechanical properties, biocompatibility, effects on the secretion of angiogenic factors and fidelity of 3D bioprinting. The results showed that adding 1% (w/v) ChiNC to 10% (w/v) GelMA improved the mechanical properties and printability of the GelMA hydrogels, promoted cell adhesion, proliferation and vascularization and enabled the printing of complex 3D scaffolds. This strategy of incorporating ChiNC to enhance the performance of GelMA biomaterials could potentially be applied to other biomaterials, thereby expanding the range of materials available for use. Furthermore, in combination with 3D bioprinting technology, this approach could be leveraged to bioprint scaffolds with complex structures, further broadening the potential applications in tissue engineering. [ABSTRACT FROM AUTHOR]

Cachexia is characterized by progressive weight loss accompanied by the loss of specific skeletal muscle and adipose tissue. Increased lactate production, either due to the Warburg effect from tumors or accelerated glycolysis effects from cachectic muscle, is the most dangerous factor for cancer cachexia. This study aimed to explore the efficiency of 2-deoxy-D-glucose (2-DG) in blocking Cori cycle activity and its therapeutic effect on cachexia-associated muscle wasting. A C26 adenocarcinoma xenograft model was used to study cancer cachectic metabolic derangements. Tumor-free lean mass, hindlimb muscle morphology, and fiber-type composition were measured after in vivo 2-DG administration. Activation of the ubiquitin-dependent proteasome pathway (UPS) and autophagic–lysosomal pathway (ALP) was further assessed. The cachectic skeletal muscles of tumor-bearing mice exhibited altered glucose and lipid metabolism, decreased carbohydrate utilization, and increased lipid β-oxidation. Significantly increased gluconeogenesis and decreased ketogenesis were observed in cachectic mouse livers. 2-DG significantly ameliorated cancer cachexia-associated muscle wasting and decreased cachectic-associated lean mass levels and fiber cross-sectional areas. 2-DG inhibited protein degradation-associated UPS and ALP, increased ketogenesis in the liver, and promoted ketone metabolism in skeletal muscle, thus enhancing mitochondrial bioenergetic capacity. 2-DG effectively prevents muscle wasting by increasing ATP synthesis efficiency via the ketone metabolic pathway and blocking the abnormal Cori cycle. [ABSTRACT FROM AUTHOR]

(Ti, Al)N coatings with different Al target power densities on the surface of M2 high-speed steel were deposited by magnetron sputtering to study the tribological properties. The phase composition, microstructure, and element distribution of coatings were characterized by x-ray diffraction, field emission scanning electron microscopy, x-ray photoelectron spectroscopy, and energy dispersive spectrometry. The results showed that the tribological properties of the coatings were closely related to the power density of the Al target. With a gradual increase in the Al target power density, the microhardness increased from 1324.7 to 2819.2 HV. Meanwhile, when Al target power density was 7.9 W/cm2, the coatings exhibit the lowest coefficient of friction (COF = 0.23). By comparison, it was found that (Ti, Al)N coatings exhibited a smooth surface, uniformly dense columnar structures, and smaller grain sizes due to the addition of Al atoms. (Ti, Al)N coatings showed a unique microstructure that determined their excellent tribological properties. [ABSTRACT FROM AUTHOR]

Background: Periodontitis is considered a risk factor for atherosclerosis, but the mechanism is not clear. It was reported that oral administration of Porphyromonas gingivalis altered the gut microbiota in mice. Gut dysbiosis and the intestinal metabolite trimethylamine N-oxide (TMAO) were verified to be associated with atherosclerosis. Therefore, the possible TMAO-related mechanism between periodontitis and atherosclerosis needs to be explored. Methods: Experimental periodontitis was established by oral administration of P. gingivalis for 2 months in ApoE−/− mice. Mouse hemi-mandibles were scanned using Micro-CT. Quantification of TMAO was performed using liquid chromatography–tandem mass spectrometry. Mouse feces were collected and the bacterial DNA was extracted, then the gut microbiota was analyzed using 16S rRNA genes. Atherosclerotic lesion areas were quantified. Livers, small intestines, and large intestines were analyzed for gene expression. Results: Aggravated atherosclerosis plaques were found in experimental periodontitis mice. Plasma TMAO, a pathogenic factor of atherosclerosis, was initially found to be increased in periodontitis mice. Changes in the composition and abundance of the intestinal microflora of periodontitis mice were found. Flavin monooxygenase 3 (FMO3), the catalyzing enzyme of TMAO in the liver, was significantly increased, accompanied by an increase of IL-6 in liver, the abnormal intestinal integrity and enhanced plasma LPS. The IL-6 and LPS were verified to be able to increase FMO3 in HepG2 cells. Conclusion: Our research discovered that experimental periodontitis in ApoE−/− mice induced gut dysbiosis and an increase in TMAO. These results suggest a possible mechanism by which periodontitis may accelerate atherosclerosis by influencing the intestinal microbes and the metabolism, which were triggered by inflammation of the liver and intestine. [ABSTRACT FROM AUTHOR]

Exposure to airborne urban particles is a contributing factor for the development of multiple types of respiratory diseases; its pathological role as a cause of lung injury is still unclear. In this study, PM2.5 soluble extract was collected, and its toxicological effect on lung pathological changes was examined. To assess its pathological mechanism, Human Monocyte-Like Cell Line, THP-1, and mouse macrophage, RAW264.7, were used to determine the effects of PM2.5 soluble extract on cell toxicity, phagocytosis, and transcriptome. We found that PM2.5 soluble extract exposure activated NF-κB and MAPK signaling pathways, then induces the production of pro-inflammatory cytokines. RNA-seq results showed that the transcription profiles, including 1213 genes, have been changed in responses to PM2.5 exposure. Additionally, PM2.5 led to phagocytic dysfunction, which may exacerbate the cause of lung injury. Exposure to PM2.5 soluble extract triggers the death of respiratory macrophages, impairs its phagocytosis capacity, thus delaying the inflammatory cell clearance in the lung, which results in chronic lung injury. [ABSTRACT FROM AUTHOR]

Background: Periodontitis is considered a risk factor for atherosclerosis, but the mechanism is not clear. It was reported that oral administration of Porphyromonas gingivalis altered the gut microbiota in mice. Gut dysbiosis and the intestinal metabolite trimethylamine N-oxide (TMAO) were verified to be associated with atherosclerosis. Therefore, the possible TMAO-related mechanism between periodontitis and atherosclerosis needs to be explored. Methods: Experimental periodontitis was established by oral administration of P. gingivalis for 2 months in ApoE−/− mice. Mouse hemi-mandibles were scanned using Micro-CT. Quantification of TMAO was performed using liquid chromatography–tandem mass spectrometry. Mouse feces were collected and the bacterial DNA was extracted, then the gut microbiota was analyzed using 16S rRNA genes. Atherosclerotic lesion areas were quantified. Livers, small intestines, and large intestines were analyzed for gene expression. Results: Aggravated atherosclerosis plaques were found in experimental periodontitis mice. Plasma TMAO, a pathogenic factor of atherosclerosis, was initially found to be increased in periodontitis mice. Changes in the composition and abundance of the intestinal microflora of periodontitis mice were found. Flavin monooxygenase 3 (FMO3), the catalyzing enzyme of TMAO in the liver, was significantly increased, accompanied by an increase of IL-6 in liver, the abnormal intestinal integrity and enhanced plasma LPS. The IL-6 and LPS were verified to be able to increase FMO3 in HepG2 cells. Conclusion: Our research discovered that experimental periodontitis in ApoE−/− mice induced gut dysbiosis and an increase in TMAO. These results suggest a possible mechanism by which periodontitis may accelerate atherosclerosis by influencing the intestinal microbes and the metabolism, which were triggered by inflammation of the liver and intestine. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the most common malignant cancers worldwide. Searching for specific cancer targets and developing efficient therapies with lower toxicity is urgently needed. HPS90 is a key chaperon protein that has multiple client proteins involved in the development of cancer. In this study, we investigated the transcriptional levels of HSP90 isoforms in cancerous and normal tissues of lung cancer patients in multiple datasets. The higher expression of HSP90AA1 in cancer tissues correlated with poorer overall survival was observed. The higher levels of transcription and expression of HSP90AA1 and the activity of AKT1/ERK pathways were confirmed in lung cancer patient tissues. In both human and mouse lung cancer cell lines, knocking down HSP90AA1 promoted cell apoptosis through the inhibition of the pro-survival effect of AKT1 by decreasing the phosphorylation of itself and its downstream factors of mTOR and BAD, as well as downregulating Mcl1, Bcl-xl, and Survivin. The knockdown also suppressed lung cancer cell proliferation by inhibiting ERK activation and downregulating CyclinD1 expression. The treatment of 17-DMAG, an HSP90 inhibitor, recaptured these effects in vitro and inhibited tumor cell growth, and induced apoptosis without obvious side effects in lung tumor xenograft mouse models. This study suggests that targeting HSP90 by 17-DMAG could be a potential therapy for the treatment of lung cancer. [ABSTRACT FROM AUTHOR]

In this paper, we consider the one-sided and the two-sided first exit problem for a jump diffusion process with semimartingale local time. Denote this process by X = { X t , t ≥ 0 } and set τ l = inf { t ≥ 0 , X t ≤ l } and τ l , u = inf { t ≥ 0 , X t ∉ (l , u) } with l < u . We first establish the existence and uniqueness of strong solutions of the stochastic differential equation (SDE) satisfied by X. Then we investigate the Laplace transforms associated with τ l and τ l , u . It turns out that the explicit expressions for those Laplace transforms can be expressed in terms of exponential functions. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) remains a worldwide healthcare concern, and the exploration of the host‐pathogen interaction is essential to develop therapeutic modalities and strategies to control Mycobacterium tuberculosis (M.tb). In this study, RNA sequencing (transcriptome sequencing) was employed to investigate the global transcriptome changes in the macrophages during the different strains of M.tb infection. THP‐1 cells derived from macrophages were exposed to the virulent M.tb strain H37Rv (Rv) or the avirulent M.tb strain H37Ra (Ra), and the M.tb BCG vaccine strain was used as a control. The cDNA libraries were prepared from M.tb‐infected macrophages and then sequenced. To assess the transcriptional differences between the expressed genes, the bioinformatics analysis was performed using a standard pipeline of quality control, reference mapping, differential expression analysis, protein‐protein interaction (PPI) networks, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Q‐PCR and Western blot assays were also performed to validate the data. Our findings indicated that, when compared to BCG or M.tb H37Ra infection, the transcriptome analysis identified 66 differentially expressed genes in the M.tb H37Rv‐infected macrophages, out of which 36 genes were up‐regulated, and 30 genes were down‐regulated. The up‐regulated genes were associated with immune response regulation, chemokine secretion, and leucocyte chemotaxis. In contrast, the down‐regulated genes were associated with amino acid biosynthetic and energy metabolism, connective tissue development and extracellular matrix organization. The Q‐PCR and Western blot assays confirmed increased expression of pro‐inflammatory factors, altered energy metabolic processes, enhanced activation of pro‐inflammatory signalling pathways and increased pyroptosis in H37Rv‐infected macrophage. Overall, our RNA sequencing‐based transcriptome study successfully identified a comprehensive, in‐depth gene expression/regulation profile in M.tb‐infected macrophages. The results demonstrated that virulent M.tb strain H37Rv infection triggers a more severe inflammatory immune response associated with increased tissue damage, which helps in understanding the host‐pathogen interaction dynamics and pathogenesis features in different strains of M.tb infection. [ABSTRACT FROM AUTHOR]

Background and Purpose: Cancer cachexia is a common cause of death among cancer patients with no currently effective treatment available. In animal models, aberrant activation of STAT3 in skeletal muscle contributes to muscle wasting. However, clinically the factors regulating STAT3 activation and the molecular mechanisms involved remain incompletely understood.Experimental Approach: The expression of HSP90 and the activation of STAT3 were detected in muscle from the patients with cancer cachexia or the tumour-bearing cachectic mice. HSP90 inhibitors, including 17DMAG (alvespimycin) and PU-H71, were administered to cachexic mice and cachexia parameters, weight loss, food intake, survival rate, body composition, serum metabolites, muscle wasting pathology and catabolic activation were analysed. The co-culture of C2C12 myotube cells with C26 conditioned media was performed to investigate the pathological mechanism involved in catabolic muscle wasting. The roles of HSP90, STAT3 and FOXO1 in myotube atrophy were explored via overexpression or knockdown.Results: An enhanced interaction between activated STAT3 and HSP90 in the skeletal muscle of cancer cachexia patients, is a crucial for the development of cachectic muscle wasting. HSP90 inhibitors 17DMAG and PU-H71 alleviated the muscle wasting in C26 and models or the myotube atrophy of C2C12 cells induced by C26 conditional medium. Prolonged STAT3 activation transactivated FOXO1 by binding directly to its promoter and triggered the muscle wasting in a FOXO1-dependent manner in muscle cells.Conclusion and Implications: The HSP90/STAT3/FOXO1 axis plays a critical role in cachectic muscle wasting, which might be a potential therapeutic target for the treatment of cancer cachexia. [ABSTRACT FROM AUTHOR]

In this paper, we study the joint Laplace transform of the sticky Brownian motion on an interval, its occupation time at zero and its integrated process. The perturbation approach of Li and Zhou [The joint Laplace transforms for diffusion occupation times, Adv. Appl. Probab.45 (2013) 1049–1067] is adopted to convert the problem into the computation of three Laplace transforms, which is essentially equivalent to solving the associated differential equations with boundary conditions. We obtain the explicit expression for the joint Laplace transform in terms of the modified Bessel function and Airy functions. [ABSTRACT FROM AUTHOR]

Statin treatment is a major prevention treatment for hypercholesterolemia and the management of patients with increased risk of cardiovascular disease (CVD) due to its protective effects. However, its long-term safety was questioned regarding its potential role in new-onset type 2 diabetes mellitus, and its effect on gene regulation in the liver is not yet fully understood. By reanalyzing the transcriptome of the livers of patients with obesity and hypercholesterolemia, this study shows a multiple module organization that is related to various clinical metabolic parameters and identified an expression hierarchical network involving cholesterol and fatty acid syntheses in the liver of statin-treated patients. The key genes of the network were validated by QPCR in the hepatocytes upon statin treatment. The upregulation of the key enzymes involving the synthesis of Acetyl-CoA and the induction of gentle global acetylation of pan-protein and histone H4 in hepatocytes were observed. The study provides an overall view of the statin effect on transcriptional and post-transcriptional regulation of genes in the liver. [ABSTRACT FROM AUTHOR]

IL-6 has been suggested to function as an autocrine mitogen in the psoriatic epidermis. The biological activity of IL-6 relies on interactions with its receptors, including the membrane-bound IL-6 receptor (mIL-6R) and soluble IL-6 receptor (sIL-6R). Our study presents data showing that the levels of plasma IL-6 and sIL-6R were elevated in psoriatic patients. Genotyping of two single-nucleotide polymorphisms (SNPs) in IL-6R (rs4845617 and rs2228145) demonstrated that the SNP IL-6R (rs4845617) rather than IL-6R (rs2228145) shows a significant association with psoriasis (P = 0.006). To verify the functions of sIL-6R, cultured keratinocytes and imiquimod (IMQ)-induced psoriatic model mice were treated with sIL-6R. We found that the presence of sIL-6R in the HaCaT cell culture medium enhanced the IL-6-induced Stat3 activation, which resulted in abnormal keratinocyte proliferation and aberrant differentiation. Furthermore, the application of sIL-6R in vivo accelerated the pathological development of the disease. Our results demonstrate for the first time that genetic polymorphisms in the IL-6R gene are associated with psoriasis disease phenotypes in a Chinese psoriatic patient population; sIL-6R-mediated trans-signaling pathway plays a pivotal role in keratinocyte proliferation and differentiation, suggesting potential therapeutics for psoriasis. Key messages: Patients with psoriasis displayed higher levels of IL-6 and sIL-6R compared with healthy controls. Analysis of genotypes revealed that IL-6R rs4845617 GG genotype associated with the risk of psoriasis. Supplement of sIL-6R further enhanced IL-6-induced Stat3 activation in keratinocytes. In vivo administration of sIL-6R accelerated, whereas sgp130FC alleviated, the pathological development of psoriasis. [ABSTRACT FROM AUTHOR]

The lotus leaf has the Janus wettability and outstanding floatability at multiphase interface. The ingenious design on lotus leaf surfaces enlightens us to fabricate the superhydrophobic/superhydrophilic binary cooperative membrane. Making use of the poor permeability of the candle soot, deposition of a layer of candle soot enables to form the Janus membrane with anisotropic wettability on different surfaces. After fixed by the hydrophobic polymer, the superhydrophobic/superhydrophilic binary cooperative membranes are prepared successfully on various membranes, such as filter paper, cotton fabric and copper mesh. The Janus membrane exhibits excellent interfacial floatability at the immiscible oil–water interface as a separator, thus affording high-performance immiscible oil/water separation without applied external pressure. [ABSTRACT FROM AUTHOR]

Understanding the genetic mechanism underlying seed size, shape, and weight is essential for enhancing soybean cultivars. High-density genetic maps of two recombinant inbred line (RIL) populations, LM6 and ZM6, were evaluated across multiple environments to identify and validate M-QTLs as well as identify candidate genes behind major and stable quantitative trait loci (QTLs). A total of 239 and 43 M-QTLs were mapped by composite interval mapping (CIM) and mixed-model-based composite interval mapping (MCIM) approaches, from which 180 and 18, respectively, are novel QTLs. Twenty-two QTLs including four novel major QTLs were validated in the two RIL populations across multiple environments. Moreover, 18 QTLs showed significant AE effects, and 40 pairwise of the identified QTLs exhibited digenic epistatic effects. Thirty-four QTLs associated with seed flatness index (FI) were identified and reported here for the first time. Seven QTL clusters comprising several QTLs for seed size, shape, and weight on genomic regions of chromosomes 3, 4, 5, 7, 9, 17, and 19 were identified. Gene annotations, gene ontology (GO) enrichment, and RNA-seq analyses of the genomic regions of those seven QTL clusters identified 47 candidate genes for seed-related traits. These genes are highly expressed in seed-related tissues and nodules, which might be deemed as potential candidate genes regulating the seed size, weight, and shape traits in soybean. This study provides detailed information on the genetic basis of the studied traits and candidate genes that could be efficiently implemented by soybean breeders for fine mapping and gene cloning, and for marker-assisted selection (MAS) targeted at improving these traits individually or concurrently. [ABSTRACT FROM AUTHOR]

With a great interest, we read the recent paper by Freire and colleagues, entitled 'The expression landscape of cachexia-inducing factors in human cancers'.1 The authors concluded that a panel of cachexia induced secreted factors (CIFs) initially used for screening of pancreatic cachectic patients2 was correlated with the cachexia prevalence and predicted patient survival in multiple types of cancers. The number of CIFs in the DEGs of each cancer was counted and used to index the weight loss and prevalence of cachexia in that cancer. The number of CIFs, range from 9 to 14 ( I Table i 1), reorganized the order of cancer landscape, which showed no correlation of the CIFs with average weight loss or prevalence of cachexia in these cancers ( I Figure i 1). [Extracted from the article]

Diabetic retinopathy (DR) is a serious neurodegenerative disease that is induced by hyperglycaemia. Oxidative stress, inflammation and endoplasmic reticulum (ER) stress are involved in the development of DR. Sulforaphane (SF) is widely found in cruciferous plants and has a protective effect against retinal neurodegeneration in diabetes, but the mechanism is unclear. In this study, we investigated the mechanism by which SF protects against photoreceptor degeneration in diabetes. In vivo, a mouse model of diabetes was established by streptozotocin (STZ) injection, and the mice were treated with/without SF. Electroretinography (ERG) and H&E staining were used to evaluate retinal function and morphology. In vitro, 661w cells were treated with AGEs with/without SF. Cell viability and apoptosis were analysed by CCK-8 assay and flow cytometry. The expression of proteins and genes was assessed by western blot and qRT-PCR. The amplitude of the a-wave was decreased and the morphology was changed in the diabetic mice, and these changes were delayed by SF treatment. The percentage of apoptotic cells was increased and the cell viability was decreased after the treatment of 661w cells with AGEs. Moreover, the expression of GRP78, Txnip and TNFα was increased, however, this increased expression was reversed by SF treatment via AMPK pathway activation. Taken together, these data show that SF can delay photoreceptor degeneration in diabetes, and the underlying mechanism is related to the inhibition of ER stress, inflammation and Txnip expression through the activation of the AMPK pathway. [ABSTRACT FROM AUTHOR]

A novel liquid-infused, patterned, porous membrane system with anti-fouling characteristics is prepared via simple co-infusion of oil and water within hydrophobic and superhydrophilic surfaces of a porous membrane, respectively. This membrane simultaneously repels the immiscible water and oil exhibiting excellent interfacial floatability at the oil–water interface as a separator, thus showing promise for use in applications in the immiscible oil/water separation industry and liquid–liquid extraction. [ABSTRACT FROM AUTHOR]

Biochar derived from straw is a potential low-cost adsorbent for metal ions and organic pollutants, but its practical application is still limited by the adsorption capacity. In this study, the correlation between the biochar's properties and pyrolysis temperature was explored. The adsorption mechanism was studied by monitoring the changes of biochar properties before and after adsorption using BET, SEM, XPS and FT-IR spectroscopy. The adsorption mechanism was revealed following the adsorption kinetics and the changes in biochar's properties before and after adsorption. The methylene blue (MB) and Pb2+ adsorption removal efficiency reached 95% at the initial concentration of 125 and 500 mg/L, respectively. Physisorption, chemisorption, and pore filling mechanisms determined the adsorption process of MB and Pb2+ on biochar. The Pb2+ adsorption process was highly affected by chemical co-precipitation at higher pyrolysis temperatures. The appearance of tar particles increased the adsorption rate of Pb2+. The biochar obtained at the pyrolysis temperature at 500, 800 and 900°C proved to be applicable for Pb2+ removal. Chemisorption and porosity dominated the MB adsorption, and biochars produced at pyrolysis temperatures of 200, 800 and 900°C are potential materials for MB removal. This study provides optimal pyrolysis conditions for transforming maize straw into valuable, low-cost materials for the removal of different pollutants. [ABSTRACT FROM AUTHOR]

This paper derives closed-form formulae for European options under a diffusion model when there exist psychological barriers and leverage effect in underlying dynamics. The state space of the proposed model is divided into different subregions by psychological barriers, and in each subregion, the model behaves like a constant elasticity of variance process. Within this framework, we derive both Laplace transform- and spectral expansion-based analytical solutions, which allow fast and accurate calculation of option prices. Numerical results are presented to explore the nontrivial properties of our model. [ABSTRACT FROM AUTHOR]

In this paper, the problem of robust fault detection is investigated for nonlinear uncertain Markovian jump systems subject to time-varying delays, Lipschitz nonlinearities and parameter uncertainties under the event-triggered protocol. The event-triggered mechanism is introduced to adjust the transmission frequency of the data sent to the remote module. An event-based fault detection method is presented to guarantee the sensitivity of residual to fault and the attenuation of the effect from the disturbance on the residual. In this way, the considered fault detection problem is solvable by testifying the feasibility of H ∞ filtering problem. By constructing the mode-dependent Lyapunov functional, new sufficient criteria are derived in terms of the linear matrix inequality technique, which insures the stochastic stability with prescribed performance for addressed MJSs. In the end, a numerical example is exploited and the validity of newly presented event-based fault detection method is shown. [ABSTRACT FROM AUTHOR]

Puerarin, an isoflavonoid rich in Radix Puerariae , has been reported to be a broadly effective regulator in various biological processes and clinic conditions. However, the role of puerarin in sepsis-induced mortality with multiple-organ injury remains unknown. Herein, we showed that puerarin potently attenuated organ injury and increased survival rate in both lipopolysaccharides (LPS) and cecal ligation and puncture (CLP) induced mouse sepsis models. It greatly suppressed systemic inflammation, determined by the serum levels of proinflammatory factors TNF-α, IL-6, IL-1β, IL-10, as well as monocyte chemotactic protein-1 (MCP-1) and C-reactive protein (CRP). Flow cytometry analysis indicated that puerarin settled overall inflammation mainly by normalizing expanded macrophages with limited effects on dendritic cells and CD4+T cells in the circulation of sepsis mice. In the liver, puerarin inhibited the transcription of inflammatory factor TNF-α, IL-6, and IL-1β and protected hepatocyte apoptosis in sepsis mouse models. In vitro, puerarin inhibited LPS-induced inflammation in LO2 hepatocytes, prevented TNF-α-mediated cell apoptosis and promoted an M2 phenotype revealed by M2 marker IL-10 and Arginase-1 (Arg-1) in LPS challenged Raw 264.7 macrophages, through the inhibition of TLR4/NF-κB/JNK pathway. In conclusion, puerarin reduced systemic inflammation and protected organ injury in sepsis mice, thus, it might provide a new modality for a better treatment of sepsis. [ABSTRACT FROM AUTHOR]

Background: Radiation to the head and neck is a well‐established risk factor for the development of carotid artery stenosis. Our objective was to identify the prevalence, incidence, and degree of carotid stenosis in patients with a history of head and neck irradiation. Methods: This study was performed according to the PRISMA guidelines. A random effects model meta‐analysis was conducted. Results: Nineteen studies comprising 1479 patients were included. The prevalence of carotid stenosis >50%, >70%, and carotid occlusion was 25% (95% CI: 19%‐32%), 12% (95% CI: 7%‐17%), and 4% (95% CI: 2%‐8%), respectively. The cumulative 12‐month incidence of carotid stenosis >50% was 4% (95% CI: 2%‐5%), the 24‐month was 12% (95% CI: 9%‐15%), and the 36‐month was 21% (95% CI: 9%‐36%). Conclusions: The yearly incidence of carotid stenosis >50% increased every year during the first 3 years following radiotherapy. We propose routine yearly Doppler ultrasound screening beginning 1 year after head and neck radiotherapy. [ABSTRACT FROM AUTHOR]

We explore the first passage problem for sticky reflecting diffusion processes with double exponential jumps. The joint Laplace transform of the first passage time to an upper level and the corresponding overshoot is studied. In particular, explicit solutions are presented when the diffusion part is driven by a drifted Brownian motion and by an Ornstein–Uhlenbeck process. [ABSTRACT FROM AUTHOR]

In this paper, we consider the probability of default for financial variables under a tractable stochastic model which can capture both the price clustering phenomenon and the jump risk. We assume that the logarithm of the price dynamics is driven by a so-called sticky double exponential jump diffusion process. In particular, the price clustering is incorporated by time changing the jump diffusion process, and the jump risk is described through a Poisson stochastic integral related to the compound Poisson process with double exponential jumps. Under such a model, we study the default events in the structural credit risk framework. The explicit solutions of Laplace transforms associated with default times are obtained. Based on the derived results, we numerically analyze the effects of the price clustering and the jump risk on the distributions of default times and on the bond's credit spreads. [ABSTRACT FROM AUTHOR]