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Through hot compression and subsequent heat treatment experiments on GH4079 superalloy, the influence of different hot deformation and heat treatment conditions on the evolution of GH4079 superalloy microstructure was studied. The evolution of grains and γ′ phases under different thermomechanical conditions was investigated. The results indicate that at deformation temperatures above 1100 °C and strain rates ranging from 0.01 to 0.1 s−1, the primary mechanism of dynamic softening in the alloy is discontinuous dynamic recrystallization (DDRX). When the deformation temperature is below 1100 °C and strain rates range from 0.01 to 0.1 s−1, both continuous dynamic recrystallization (CDRX) and DDRX are the main dynamic softening mechanisms. Due to high strain energy accumulation, the samples deformed at lower temperatures (below 1100 °C) and then solution-treated at 1120 °C for 8 h exhibit significant increases in recrystallization volume fraction and recrystallization grain size. Conversely, the samples deformed at higher temperatures (above 1100 °C) and then solution-treated at 1120 °C for 8 h show minimal changes in recrystallization volume fraction and recrystallization grain size. After solution treatment at 1140 °C, the grain size of the alloy significantly increases. The samples deformed at higher strain rates exhibit the evolution of fine γ′ phases into elongated rod shapes during solution treatment, while larger γ′ phases undergo splitting processes.

Due to anthropogenic and long-term geological factors, radionuclide leakage may occur in deep geological repositories of radioactive waste when groundwater infiltrates a failed waste canister. The released radionuclides can migrate to near and far field regions through groundwater, posing a serious threat to the ecological environment and human health. As a consequence, knowledge of radionuclide speciation in groundwater is essential for understanding their transport behavior. Uranium is one of the key elements of significant concern for deep geological disposal of high-level radioactive waste. In this study, the uranium species in groundwater from boreholes BS03(pH=9.43) and BS05(pH=7.51) located at the Beishan area(Gansu province) were calculated by the hydrogeochemical software PHREEQC(version 3). The effects of pH, temperature, and initial uranium concentrations on ternary uranyl species are presented. The results indicate that UO2CO3(aq) and (UO2)2CO3(OH)\begin{document}$_3^- $\end{document} are the dominant species in a mildly acidic condition, while CaUO2(CO3)\begin{document}$_3^{2-} $\end{document} and Ca2UO2(CO3)3(aq) are the major species in neutral and weakly alkaline conditions. In BS05 groundwater, the concentration of Ca2+(5.11 mmol/L) is about three times higher than that of Mg2+(1.58 mmol/L). However, the concentration of calcium uranyl carbonate is estimated to be about 250 times higher than that of magnesium uranyl carbonate(MgUO2(CO3)\begin{document}$ _3^{2-}$\end{document}). With an increase of temperature, Ca2UO2(CO3)3(aq), CaUO2(CO3)\begin{document}$_3^{2-} $\end{document} and UO2(CO3)\begin{document}$_3^{4-} $\end{document} concentrations progressively diminish. At uranium concentrations between 4×10−4 and 1×10−1 mmol/L (25 ℃), the dominant uranium species, in order of decreasing concentration are: Ca2UO2(CO3)3(aq)(x＞62%)＞CaUO2(CO3)\begin{document}$_3^{2-} $\end{document}(x≈35%)＞MgUO2(CO3)\begin{document}$_3^{2-} $\end{document}/UO2(CO3)\begin{document}$_3^{4-} $\end{document}(x≈1%), irrespective of the concentrations of Ca2+, Mg2+, and Na+. In the near-neutral and slightly alkaline conditions, the results suggest that the formation of neutral Ca2UO2(CO3)3(aq) and anionic CaUO2(CO3)\begin{document}$_3^{2-} $\end{document} in Beishan groundwater reduces the distribution coefficient between uranium and environmental geo-medium, thereby enhancing the mobility and migration potential of uranium. The research findings contribute to understanding the transport and release mechanisms of uranium, as well as interactions between uranium species and engineered and natural barriers.

This work systematically investigated the coarsening, dissolution, and morphological evolution behavior of γ′ precipitates in GH4742 superalloy through carefully designed heat treatment experiments. During long-term aging processes at 650 °C, 750 °C, and 850 °C, the coarsening model of γ′ precipitates followed the classic function of r3 vs. t, consistent with the classical Lifshitz-Slyozov-Wagner (LSW) coarsening model (diffusion-controlled). Due to higher diffusion coefficients of γ′ forming elements at higher temperatures, the coarsening rate K increased with aging temperature. The dynamical models for the dissolution of primary γ′ precipitates were established during sub-solvus (1080 °C) and super-solvus (1120 °C) heat treatment processes. The results indicated rapid dissolution of primary γ′ precipitates in the initial stages of solution heat treatment, with the dissolution rate gradually decreasing as the treatment time extended, approaching the γ′ precipitate size at thermodynamic equilibrium. During subsequent slow cooling at 14 °C/min after super-solvus (1120 °C) heat treatment, irregular-shaped γ′ precipitates formed through “aggregation” of adjacent γ′ precipitates, followed by “splitting” into smaller γ′ precipitates during growing up. Conversely, during subsequent slow cooling at 14 °C/min after sub-solvus (1080 °C) heat treatment, irregular-shaped γ′ precipitates were mainly controlled by unstable growth and “splitting” of cubic-shaped γ′ precipitates. For individual γ′ precipitates, the portion undergoing unstable growth (protrusions) did not undergo further splitting.

GH4742 alloy is a kind of precipitation-hardened superalloy, which is widely used in turbine disc, compressor disc, bearing ring and other parts due to its excellent high temperature mechanical properties. In this paper, high-temperature tensile comparison experiments were carried out at four temperatures, 1050 °C, 1080 °C, 1110 °C and 1140 °C, between alloy A containing a fan-shaped structure and alloy B without a fan-shaped structure. The results show that the tensile strength and plasticity of alloy A at 1050 °C are superior to those of alloy B. With the increase of temperature, the difference of tensile strength and plasticity between alloy A and B decreases gradually. By analyzing the fracture, both alloy A and B were found to have a large number of tough dimples, which showed ductile fracture characteristics. But alloy B was found to have some icing-like fracture at 1050 °C, which showed some brittle fracture characteristics. After 1110 °C, the difference in tensile strength and plasticity between alloy A and B almost disappears because γ′ phase is completely dissolved in the matrix. TEM results show that dislocations gather around the large-size γ′ phase, and for the small-size γ′ phase, dislocations tend to cut into γ′ phase directly. The results show that the existence of fan-shaped structure is beneficial to the high temperature tensile properties of GH4742 alloy, which has a certain reference effect on the production of GH4742 alloy in the future.

Abstract The nanoreactor holds great promise as it emulates the natural processes of living organisms to facilitate chemical reactions, offering immense potential in catalytic energy conversion owing to its unique structural functionality. Here, we propose the utilization of precisely engineered carbon spheres as building blocks, integrating micromechanics and controllable synthesis to explore their catalytic functionalities in two-electron oxygen reduction reactions. After conducting rigorous experiments and simulations, we present compelling evidence for the enhanced mass transfer and microenvironment modulation effects offered by these mesoporous hollow carbon spheres, particularly when possessing a suitably sized hollow architecture. Impressively, the pivotal achievement lies in the successful screening of a potent, selective, and durable two-electron oxygen reduction reaction catalyst for the direct synthesis of medical-grade hydrogen peroxide disinfectant. Serving as an exemplary demonstration of nanoreactor engineering in catalyst screening, this work highlights the immense potential of various well-designed carbon-based nanoreactors in extensive applications.

ABSTRACT The pharmacological activation of peroxisome proliferator‐activated receptor gamma (PPARγ) is a convenient and promising strategy for promoting beige adipocyte biogenesis to combat obesity‐related metabolic disorders. However, thiazolidinediones (TZDs), the full agonists of PPARγ exhibit severe side effects in animal models and in clinical settings. Therefore, the development of efficient and safe PPARγ modulators for the treatment of metabolic diseases is emerging. In this study, using comprehensive methods, we report a previously unidentified ligand‐binding pocket (LBP) in PPARγ and link it to beige adipocyte differentiation. Further virtual screening of 4097 natural compounds based on this novel LBP revealed that saikosaponin A (NJT‐2), a terpenoid compound, can bind to PPARγ to induce coactivator recruitment and effectively activate PPARγ‐mediated transcription of the beige adipocyte program. In a mouse model, NJT‐2 administration efficiently promoted beige adipocyte biogenesis and improved obesity‐associated metabolic dysfunction, with significantly fewer adverse effects than those observed with TZD. Our results not only provide an advanced molecular insight into the structural ligand‐binding details in PPARγ, but also develop a linked selective and safe agonist for obesity treatment.

Subject-specific spinal musculoskeletal modeling can help understand the spinal loading mechanism during human locomotion. However, existing literature lacks methods to identify the maximum isometric strength of individual spinal muscles. In this study, a muscle strength identification method combining isokinetic testing and musculoskeletal simulations was proposed, and the influence of muscle synergy and intra-abdominal pressure (IAP) on identified spinal muscle strength was further discussed. A multibody dynamic model of the spinal musculoskeletal system was established and controlled by a feedback controller. Muscle strength parameters were adjusted based on the measured isokinetic moments, and muscle synergy vectors and the IAP piston model were further introduced. The results of five healthy subjects showed that the proposed method successfully identified the subject-specific spinal flexor/extensor strength. Considering the synergistic activations of antagonist muscles improved the correlation between the simulated and measured spinal moments, and the introduction of IAP slightly increased the identified spinal extensor strength. The established method is beneficial for understanding spinal loading distributions for athletes and patients with sarcopenia.

Abstract The requirement for cryogenic supramolecular self‐assembly of amphiphiles in subzero environments is a challenging topic. Here, the self‐assembly of lamellar lyotropic liquid crystals (LLCs) are presented to a subzero temperature of −70 °C. These lamellar nanostructures are assembled from specifically tailored ultra‐long‐chain surfactant stearyl diethanolamine (SDA) in water/glycerol binary solvent. As the temperature falls below zero, LLCs with a liquid‐crystalline Lα phase, a tilted Lβ phase, and a new folded configuration are obtained consecutively. A comprehensive experimental and computational study is performed to uncover the precise microstructure and formation mechanism. Both the ultra‐long alkyl chain and head group of SDA play a crucial role in the formation of lamellar nanostructures. SDA head group is prone to forming hydrogen bonds with water, rather than glycerol. Glycerol cannot penetrate the lipid layer, which mixes with water arranging outside of the lipid bilayer, providing an ideal anti‐freezing environment for SDA self‐assembly. Based on these nanostructures and the ultra‐low freezing point of the system, a series of novel cryogenic materials are created with potential applications in extremely cold environments. These findings would contribute to enriching the theory and research methodology of supramolecular self‐assembly in extreme conditions and to developing novel anti‐freezing materials.

Abstract Background Adolescent idiopathic scoliosis (AIS) is the most common developmental spine disorder among children. It is characterized by a lateral deviation of the spine that gives rise to the distinctive “S” or “C” shaped bending of the spine. The Lin School of Lingnan Region (LSLR), one of the prominent schools for bare-handed orthopaedic manipulation in southern China, provides preliminary evidences that the orthopaedic manipulation techniques help to correct deviations of the spine. Previous research found that Orthopaedic Manipulation Techniques of LSLR (OMT-LSLR) could reduce the Cobb’s angles in patients with AIS. Therefore, the current study aims to investigate the effectiveness and safety of the OMT-LSLR in treating teenagers with AIS. Methods In this participant-and-assessor-blinded randomized controlled clinical trial, 50 participants identified AIS without surgical indications will be recruited and randomized into two groups to receive physiotherapy scoliosis-specific exercises training with either orthopaedic manipulation or sham manipulation treatment for 16 weeks, followed by post-treatment visits at week 24. Primary outcome measure is the change of Scoliosis Research Society-22 (SRS-22) questionnaire score. Secondary outcome measures include Traditional Chinese version of Spinal Appearance Questionnaire (TC-SAQ) score, Italian Spine Youth Quality of Life (ISYQOL) score, the change of Cobb’s angle measured by Xray, and the change of Cobb’s angle, spinal rotation and muscle volume measured by three-dimensional (3D) ultrasound. The trial will be conducted at the Chinese University of Hong Kong Chinese Medicine Specialty Clinic cum Clinical Teaching and Research Centre in Hong Kong (CUHK-CMSCTRC). Discussion The results of this study will establish comprehensive clinical evidence about the efficacy and safety of the Orthopaedic Manipulation Techniques of the Lin School of Lingnan Region in the Treatment of Adolescent Idiopathic Scoliosis. One of the characteristics of this trial is that it is a participant-and-assessor-blinded randomized controlled clinical trial with sham manipulation. The study would also apply three-dimensional (3D) ultrasound technology to investigate the relationship between the change of the muscle volume and the spinal curve. Trial registration The trial is registered on ClinicalTrials.gov (Identifier: NCT05639023 ) on December 6, 2022.

Abstract This study aims to improve the performance of automotive battery thermal management systems (BTMS) to achieve more efficient heat dissipation and thus reduce hazards during driving. Firstly, the research parameters and properties of composite thermally conductive silicone materials are introduced. Secondly, the heating principle of the power battery, the structure and working principle of the new energy vehicle battery, and the related thermal management scheme are discussed. Finally, the research results are presented from the experimental test and controller design. In addition, to achieve the research goal, the composite thermally conductive silica gel plate (CSGP) material is studied in detail and parametrically analyzed, and the heating mechanism of the power battery is discussed in depth. The temperature characteristics after adding CSGP are experimentally tested, and the controller of the BTMS of the new energy vehicle is designed, including hardware circuits and software modules. The findings show that the temperature characteristics of the battery module have obvious limitations without CSGP. When the battery module operates at a 4C magnification, the temperature exceeds the safety threshold by 38.4%, with particular potential safety risks. Then, the maximum temperature of the battery module with CSGP can be controlled within 50 °C, and the temperature characteristics are prominently improved. Lastly, the controller of the BTMS is tested, and the results reveal that it has remarkable voltage recovery ability. According to the research results, the performance of automotive BTMS can be significantly improved, and better heat dissipation can be effectively achieved by adding CSGP. This helps reduce the hazards of driving. Moreover, the designed controller performs well in voltage recovery, providing solid theoretical support for further developing the CSGP battery management system.

The microstructure of a compressed explosive solid is closely related to its shock sensitivity and mechanical properties. In this study, ultra-small-angle and small-angle X-ray scattering (USAXS and SAXS) techniques were combined to explore the hierarchical microstructure of die-pressed 2,4,6-trinitro-1,3,5-benzenetriamine (TATB) discs obtained from nanostructured TATB (nano-TATB) powder as the precursor. Using the Guinier-Porod model, the pseudo-invariants, and Porod's law, this study analyzed the microstructures of the materials on a nanometer scale to track the changes in void size, porosity, and interfacial area, which reflected the response of TATB under applied pressures of 1, 2, 5, 10, 15 ​kN and 30 ​kN. Results show that there existed three populations of voids in the measured q range. The intergranular voids with sizes of tens of nanometers were sensitive to low pressures (15 ​kN), as indicated by the decrease in the volume fractal dimension. Porosities of the voids with sizes of 1–900 ​nm, which were determined by the pseudo-invariants obtained from the scattering data, decreased from 6% to 1% as the pressures increased from 1 ​kN to 30 ​kN. The response of these structural parameters to external pressures implies that the main densification mechanisms under die compression include the flow, fracturing, and plastic deformation of the TATB granules. This study provides a direct insight into the structural evolution of TATB during compression.

In this study, focused ion beam (FIB) and transmission electron microscopy (TEM) were used to investigate the morphology, composition, crystal structure, and phase interface growth orientation of the LaAlO3-Ti(C,N)-(Ti,Nb,Mo)C complex inclusion in GH4742 alloy. Based on the theory of lattice mismatch and the thermodynamic model of inclusion formation, the formation mechanism of composite inclusions was studied. Crystallographic analysis showed that Ti(C,N) grew on the LaAlO3 substrate, and its growth was restricted by the parallel orientation relationship with the LaAlO3 substrate. The (0006¯)LaAlO3//(1¯11)Ti(C,N) was the lowest lattice mismatch plane between the two phases, with a 1D lattice mismatch of 9.68% and a 2D lattice mismatch of 10.05%. The distance difference between two parallel planes was compensated by dislocations and lattice distortions. Ti(C,N) had lower lattice mismatch with TiC and LaAlO3, making it easier to grow on the LaAlO3 nucleus. Thermodynamic calculations indicate that oxides exist in solid form within the molten alloy. As the temperature decreases, TiN precipitates in the alloy melt, while TiC precipitates during the solidification process. These results provide an explanation for the formation process of the complex three-layer structure of the complex inclusions.

Abstract Background Characterizing the unique immune microenvironment of each tumor is of great importance for better predicting prognosis and guiding cancer immunotherapy. However, the unique features of the immune microenvironment of triple negative breast cancer (TNBC) compared with other subtypes of breast cancer remain elusive. Therefore, we aimed to depict and compare the immune landscape among TNBC, human epidermal growth factor receptor 2‐positive (HER2+) breast cancer, and luminal‐like breast cancer. Methods Single‐cell RNA sequencing (scRNA‐seq) was performed on CD45+ immune cells isolated from human normal breast tissues and primary breast tumors of various subtypes. By analyzing the scRNA‐seq data, immune cell clusters were identified and their proportions as well as transcriptome features were compared among TNBC, human HER2+ breast cancer, and luminal‐like breast cancer. Pseudotime and cell‐cell communication analyses were also conducted to characterize the immune microenvironment. Results ScRNA‐seq data of 117,958 immune cells were obtained and 31 immune clusters were identified. A unique immunosuppressive microenvironment in TNBC was decoded as compared to that in HER2+ or luminal‐like breast cancer, which was characterized by higher proportions of regulatory T cells (Tregs) and exhausted CD8+ T cells and accompanied by more abundant plasma cells. Tregs and exhausted CD8+T cells in TNBC exhibited increased immunosuppression signature and dysfunctional scores. Pseudotime analyses showed that B cells tended to differentiate to plasma cells in TNBC. Cell‐cell communication analyses indicated that these unique features are fostered by the diversified T cell‐B cell crosstalk in TNBC. Based on the T cell‐B cell crosstalk, a prognostic signature was established that could effectively predict the prognosis status for patients with TNBC. Additionally, it was found that TNBC had a higher proportion of cytotoxic natural killer (NK) cells, whereas HER2+ or luminal‐like breast cancer lost this feature, suggesting that HER2+ or luminal‐like breast cancer, but not TNBC, may benefit from NK‐based immunotherapy. Conclusions This study identified a distinct immune feature fostered by T cell‐B cell crosstalk in TNBC, which provides better prognostic information and effective therapeutic targets for breast cancer.

Numerical modeling and industrial experiment were used to study the entire vacuum arc remelting (VAR) process of 660 mm GH4742 superalloy. In order to calculate the electromagnetic field, flow field, temperature field, and melt pool shape change throughout the entire VAR process, a 2D axisymmetric model with coupled multi-physical fields matching industry trials was constructed. The microstructure and elemental distribution conditions in the large-size GH4742 ingot were analyzed in combination with the industrial ingot dissection experiment, and the most likely locations of freckle defects were predicted. According to the research, the melt pool has two clockwise flow fields that are affected by buoyancy and Lorentz forces. The melt pool depth deepens gradually as melting proceeds, with a maximum melt pool depth of 0.32 m and a paste zone width of 0.16 m. Although the ingot's elemental distribution is largely consistent, there is microsegregation between the dendrites. Where the freckle is most likely to appear, at (0.322, 0.075), the Rayleigh has a great value of 1.1. For melt pool form and dendritic spacing throughout the entire melting process, the results of the industrial ingot dissection experiment and the simulation results show good agreement, proving the accuracy of the thermal history and solidification microstructure calculation for the entire melting process. Furthermore, the prospect of combining numerical simulation with a special material database for accurate defect prediction is proposed.

There are totally 93 fluorine aromatic scaffolds containing drugs approved by U.S. Food and Drug Administration from 2002 to 2022. The proportion of drugs containing fluorinated aromatic skeleton in approved drugs is increasing in recent ten years, which indicates the unique and important attributes of the fluorine atom. The introduction of fluorinated fragments into molecules can influence structure conformation, intrinsic potency and selectivity and pharmacokinetic properties productively. Additionally, 18F has been applied as a significant and useful positron emission tomography isotope for in vivo imaging technology. This review is mainly concentrated on the application and synthesis methods of 93 fluorine aromatic scaffolds containing drugs approved by the US FDA from 2002 to 2022. We hoped that this deep insight perspective into the synthetic methods for the delivery of these fluorine aromatic scaffolds containing drugs could offer practical and creative inspirations for the application and development of fluorine atom in new drug discovery.

The development of efficient and low‐cost bifunctional catalysts for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is imperative but remains challenging in rechargeable zinc–air batteries. Herein, a metal oxidation‐assisted approach is developed for the facile synthesis of a highly efficient bifunctional catalyst (Co@NC@LDHs) which is composed of layered double hydroxides (LDHs) nanosheets in situ vertically grown on the surface of hollow carbon nanoframes encapsulating Co nanoparticles (Co@NC). Specifically, the vertical LDHs distributing on the carbon surface ensure the maximized number of accessible active sites and the interaction between LDHs with the carbon matrix. The hierarchically structured bifunctional Co@NC@LDHs display an overpotential of 0.33 V at 10 mA cm−2 for OER and a half‐wave potential of 0.88 V for ORR. The potential gap (ΔE) of Co@NC@LDHs is calculated to be 0.68 V, outperforming the mixed Pt/C + RuO2 catalysts (ΔE = 0.77 V), manifesting its superior bifunctional electrocatalysis performance. Moreover, the Zn–air batteries based on Co@NC@LDHs electrocatalyst exhibit a high peak power density (185.2 mW cm−2) and excellent durability (5.0 mA cm−2 over 500 h). This work may provide a facile strategy for the fabrication of LDHs on carbon substrate, acting as efficient catalysts for broad energy‐related applications.

The content and proportion of sugars and acids in tomato fruit directly affect its flavor quality. Previous studies have shown that 5-aminolevulinic acid (ALA) could promote fruit ripening and improve its aroma quality. In order to explore the effect of ALA on sugar and acid quality during tomato fruit development, 0, 100, and 200 mg L−1 ALA solutions were sprayed on the fruit surface 10 days after pollination of the fourth inflorescence, and the regulation of ALA on sugar, acid metabolism and flavor quality of tomato fruit was analyzed. The results showed that ALA treatment could enhance the activities of acid invertase (AI), neutral invertase (NI), and sucrose synthase (SS), reduce the activity of sucrose phosphate synthase (SPS), up-regulate the expression of SlAI, SlNI and SlSS, change the composition and content of sugar in tomato fruit at three stages, significantly increase the content of sugars in fruit, and promote the accumulation of sugars into flesh. Secondly, ALA treatments increased the activities of phosphoenolpyruvate carboxykinase (PEPC), malic enzyme (ME), and citrate synthase (CS), up-regulated the expression of SlPPC2, SlME1, and SlCS, and reduced the citric acid content at maturity stage, thereby reducing the total organic acid content. In addition, ALA could also increase the number and mass fraction of volatile components in mature tomato fruits. These results indicated that exogenous application of ALA during tomato fruit development could promote the formation of fruit aroma quality and were also conducive to the formation of fruit sugar and acid quality.

Backgrounds: Gao-Liang-Huo decoction (GLH), a traditional Chinese medicine consisting of gao liangjiang (the roots or tubers of Alpinia offinarum Hance) and guang huoxiang (the aerial parts of Pogostemon cablin (Blanco) Benth.), has been shown an effective therapeutic efficacy for ulcerative colitis (UC). However, the active compounds and underlying mechanisms involved in GLH treatment of UC remains unclear. This study aims to investigate the pharmacological mechanism of GLH on UC using an integrated strategy of metabolomics and network pharmacology. Methods: The experimental mice UC model was induced using dextran sulfate sodium (DSS). The disease activity index (DAI), colonic mucosa damage index (CMDI), biochemical assays, and histopathological analysis were used to evaluate the pharmacological effect of GLH. The LC/MS-based metabolomics was used for investigation of serum metabolites and metabolic pathways regulated by GLH. The potential targets and pathways of the active compounds in GLH were further explored using network pharmacology. Finally, the underlying mechanism of GLH on UC was verified by molecular docking and immunohistochemistry (IHC). Results: The pharmacological experiments showed that GLH significantly ameliorated the DAI, CMDI, MDA, MPO, and histopathological changes in DSS-induced UC. The 15 metabolites were identified by metabolomics, such as L-tryptophan, taurocholic acid, glycocholic acid, 3-indolebutyric acid, and tryptophol. These metabolites were found to be enriched in tryptophan metabolism, glycerophospholipid metabolism, and citrate cycle (TCA cycle). The results of network pharmacology revealed the key targets, such as PIK3CA, PIK3R1, JAK1, JAK2, and JAK3, mainly involved in the PI3K-AKT, JAK-STAT, and T-cell receptor signaling pathways. Molecular docking showed high affinity interaction of quercetin, isorhamnrtin, poriferast-5-en-3beta-ol, 1,7-diphenyl-5-hydroxy-3-heptanone, and medicarpin with PIK3CA, PIK3R1, JAK1, JAK2, and JAK3, respectively. Finally, the immunohistochemistry (IHC) results indicated that GLH regulated the PI3K-AKT pathway with decreased expression levels of PI3KCA and p-AKT in DSS-induced UC. Based on integration of pharmacological experiments, network pharmacology, and metabolomics suggested that GLH might improve DSS-induced US by modulating tryptophan metabolism, glycerophospholipid metabolism, PI3K-AKT, JAK-STAT, and T-cell receptor signaling pathways. Conclusions: This study highlights the potential of combining metabolomics and network pharmacology as a promising strategy for exploring the potential mechanism of TCMs.

The challenge in synthesizing high-entropy ceramic (HEC) nanopowders is to suppress severe grain coarsening and particle agglomeration, which occur at elevated temperatures. This challenge could be addressed by the polyacrylamide gel method. In this work, single-phase high-entropy (La0.2Nd0.2Sm0.2Gd0.2Yb0.2)2Zr2O7 and (La0.2Nd0.2Y0.2Eu0.2Gd0.2)2Zr2O7 nanopowders without agglomeration were successfully synthesized using the polyacrylamide gel method for the first time. The results showed that phase composition, particle size, and agglomeration degree of the nanopowders were greatly influenced by the molar ratio of acrylamide (AM)/Zr and calcination temperature. These as-synthesized high-entropy zirconate (HEZ) nanopowders could be sintered into fully dense ceramics at 1500 ℃ for 2 h. These HEZ nanopowders showed a phase transformation from a defect-fluorite phase to a pyrochlore phase with the increase of sintering temperature. Additionally, two-step sintering of these nanopowders was conducted, and the HEZ ceramics with fine grains were prepared. The polyacrylamide gel method is simple and easily operated, which is a facile approach of producing the HEC nanopowders with excellent sinterability.

The microstructure evolution of GH4742 superalloy under the coupling action of hot deformation and heat treatment was studied by isothermal compression and then solvus heat treatment (SHT), with particular attention focused on the interaction mechanism between γ′ precipitates and dynamic recrystallization (DRX) grains. The deformation of material below the γ′ solvus temperature (1020–1050 °C) by DRX was retarded because of the strong pinning effect of γ′ precipitates. At a strain of 0.6 and all strain rates (0.01–1 s−1), a necklace-like microstructure formed with fine DRXed grains (∼2 μm) and a small DRXed fraction (

The layered double hydroxide (LDH) has been practically applied in the field of tribology and materials science due to its unique physicochemical properties, weak bonding, flexible structural composition, and adjustable interlayer space. In this work, a series of ultrathin and flexible composition of Ni-Fe LDH samples were prepared via a cost-effective room-temperature co-precipitation process. Then, they were mechanically dispersed into GTL base oil and their lubricating performance were tested by a four-ball tribometer. It is found that the variation of Ni-Fe ratio of Ni-Fe LDH has a great influence on the improvement of lubricating performance of GTL base oil. At the same concentration (0.3 mg/mL), the Ni-Fe LDH with Ni/Fe ratio of 6 was demonstrated to exhibit the best lubricating performance and the AFC, WSD, the wear volume, surface roughness and average wear scar depth decreased 51.3%, 30.8%, 78.4%, 6.7% and 50.0%, respectively. SEM-EDS and X-ray photoelectron spectra illustrated that the tribo-chemical film consisting of iron oxides and NiO with better mechanical properties formed and slowly replaced the physical film, which resists scuffing and protect solid surface from severe collisions.

Mesoporous materials containing heteroelements have a huge potential for use as catalysts, exchangers, and adsorbents due to their tunable nanometer-sized pores and exceptionally large internal surfaces accessible to bulky organic molecules. In the present work, ordered mesoporous silica containing Ni atoms as active sites was synthesized by a new low-temperature method of condensation of silica precursors on a micellar template from aqueous solutions in the presence of nickel salt. The homogeneity of the resulting product was achieved by introducing ammonia and ammonium salt as a buffer to maintain a constant pH value. The obtained materials were characterized by nitrogen sorption, X-ray and neutron diffraction, scanning electron microscopy, infrared spectroscopy, and thermal analysis. Their morphology consists of polydisperse spherical particles 50–300 nm in size, with a hexagonally ordered channel structure, high specific surface area (ABET = 900–1200 m2/g), large pore volume (Vp = 0.70–0.90 cm3/g), average mesopore diameter of about 3 nm, and narrow pore size distribution. Adsorption tests for methylene blue show sorption capacities reaching 39–42 mg/g at alkaline pH. The advantages of producing nickel silicates by this method, in contrast to precipitation from silicon alkoxides, are the low cost of reagents, fire safety, room-temperature processing, and the absence of specific problems associated with the use of ethanol as a solvent, as well as the absence of the inevitable capture of organic matter in the precipitation process.

Small cell cervical carcinoma (SCCC) is a rare but aggressive malignancy. Here, the authors report human papillomavirus features and genomic landscape in SCCC via high-throughput sequencing methods and identify MYC, SOX, NR4A, ANKRD and CEA family genes as HPV-integrated hotspots.

Extraction process for Q-markers from Rosa roxburghii using response surface methodology was optimized and HPLC method was established for simultaneous determination of their content. The extraction process of Q-marker from the root of Rosa roxburghii Tratt was optimized by single factor experiments and response surface methodology, and the four Q-markers (triterpenoids) in different parts (root, stem, leaf and fruit) of Rosa roxburghii Tratt were analyzed. Results showed that, through single factor experiments, the important factors affecting the yield of Q-markers were determined as solvent dosage, ethanol concentration, extraction time and extraction times. Response surface methodology was used to optimize the extraction process of Q-markers from Rosa roxburghii. The optimal extraction conditions were as follows: The solvent dosage was 1:25 g/mL, 70% ethanol was added, the extraction time was 30 min, and then the material was refluxed for 2 h. The yield of four Q-markers from the Rosa roxburghii leaves was 2.64%, including 0.99% of Kaji-ichigoside F1, 0.72% mg/g of rosamultin, 0.43% of rosolic acid and 0.51% of 2α,19α-dihydroxyursolic acid. The total content of Q-markers in different parts of Rosa roxburghii Tratt was in the order of leaves, roots, stems and fruits. This study would provide scientific reference for quality evaluation of Rosa roxburghii and development and utilization of total triterpenoids.

The transmission line has long transmission distance and complex channel environment.Impacts caused by large construction machinery occur from time to time.The existing anti-collision monitoring scheme of transmission line mainly depends on manual implementation, which not only consumes a lot of human resources, but also is difficult to ensure the monitoring coverage.Therefore, an anti-collision on-line early warning method for construction machinery around the transmission line was proposed.This method innovatively used intelligent sensors and compressed sensing algorithm to realize the automatic on-line early warning of construction machinery threats in the transmission line channel.The pixel distribution characteristics, shape characteristics and distance characteristics of the target were collected by the camera module and microwave ranging module, and transmitted to the background.The background server used the established offline feature target database to realize the research and judgment results of the target through compressed sensing algorithm, and sent out early warning to the threatening target in time.The experimental results show that the recognition accuracy of the proposed algorithm can reach 96.34%, and can provide reliable early warning results for the transmission inspection department.

Melatonin plays a vital role in plant growth and development. In this study, we treated hydroponically grown tomato roots with various concentrations of exogenous melatonin (0, 10, 30, and 50 μmol·L−1). We utilized root scanning and microscopy to examine alterations in root morphology and cell differentiation and elucidated the mechanism by which melatonin regulates these changes through the interplay with endogenous hormones and relevant genes. The results showed that for melatonin at concentrations ranging between 10 and 30 μmol·L−1, the development of lateral roots were significantly stimulated, the root hair growth was enhanced, and biomass accumulation and root activity were increased. Furthermore, we elucidated that melatonin acts as a mediator for the expression of genes, such as SlCDKA1, SlCYCA3;1, SlARF2, SlF3H, and SlKT1, which are involved in the regulation of root morphology changes. Additionally, we observed that melatonin influences the levels of endogenous hormones, including ZT, GA3, IAA, ABA, and BR, which subsequently impact the root morphology development of tomato roots. In summary, this study shows that tomato root morphology can be promoted by the optimal concentration of exogenous melatonin (10–30 μmol·L−1).

Stable actinide colloids and nanoparticles are of interest because of their potential to affect the transportation of radionuclides in the near-field of a nuclear waste repository. At high concentrations, thorium(IV) can precipitate to form intrinsic colloids. In the present study, polynuclear thorium colloids and thorium dioxide crystallites, formed by the condensation of hydrolyzed Th4+ solutions (3 mM; initial pH 5.5) aged for up to 18 months, were studied using small-angle X-ray scattering. Scattering profiles were fitted using a unified Guinier/power-law model (Beaucage model) to extract the radii of gyration and Porod exponents. Analysis of the scattering profiles from a dispersion aged for 5 months indicated that both polymer coils and more compacted structures (radius of gyration Rg ≃ 10 nm) were present, which translated in the Kratky plots as a plateau and a peak maximum, respectively. After 18 months, the SAXS data were consistent with the presence of agglomerates of ThO2 particles suspended in aqueous solution (pH 3.2; [Th] = 1.45 mM). The measured radius of gyration (Rg) of the agglomerates was 5.8 nm, whereas the radius of the ThO2 particles was 2.5 nm.

In the era of personalized oncology, there have been accelerated efforts to develop clinically relevant platforms to test drug sensitivities of individual cancers. An ideal assay will serve as a diagnostic companion to inform the oncologist of the various treatments that are sensitive and insensitive, thus improving outcome while minimizing unnecessary toxicities and costs. To date, no such platform exists for clinical use, but promising approaches are on the horizon that take advantage of improved techniques in creating human cancer models that encompass the entire tumor microenvironment, alongside technologies for assessing and analyzing tumor response. This review summarizes a number of current strategies that make use of intact human cancer tissues as organotypic cultures in drug sensitivity testing.

PurposeThe aim of this study was to improve the intratumoral accumulation of an antibody–drug conjugate (ADC) and minimize its off-target toxicity, SKB264, a novel anti-trophoblast antigen 2 (TROP2) ADC that was developed using 2-methylsulfonyl pyrimidine as the linker to conjugate its payload (KL610023), a belotecan-derivative topoisomerase I inhibitor. The preclinical pharmacologic profiles of SKB264 were assessed in this study.MethodsThe in vitro and in vivo pharmacologic profiles of SKB264, including efficacy, pharmacokinetics–pharmacodynamics (PK-PD), safety, and tissue distribution, were investigated using TROP2-positive cell lines, cell-derived xenograft (CDX), patient-derived xenograft (PDX) models, and cynomolgus monkeys. Moreover, some profiles were compared with IMMU-132.ResultsIn vitro, SKB264 and SKB264 monoclonal antibody (mAb) had similar internalization abilities and binding affinities to TROP2. After cellular internalization, KL610023 was released and inhibited tumor cell survival. In vivo, SKB264 significantly inhibited tumor growth in a dose-dependent manner in both CDX and PDX models. After SKB264 administration, the serum or plasma concentration/exposure of SKB264 (conjugated ADC, number of payload units ≥1), total antibody (Tab, unconjugated and conjugated mAb regardless of the number of the payload units), and KL610023 in cynomolgus monkeys increased proportionally with increasing dosage from 1 to 10 mg/kg. The linker stability of SKB264 was significantly enhanced as shown by prolonged payload half-life in vivo (SKB264 vs. IMMU-132, 56.3 h vs. 15.5 h). At the same dose, SKB264’s exposure in tumor tissue was 4.6-fold higher than that of IMMU-132.ConclusionsCompared with IMMU-132, the longer half-life of SKB264 had a stronger targeting effect and better antitumor activity, suggesting the better therapeutic potential of SKB264 for treating TROP2-positive tumors.

Electrochemical energy storage (EES) devices are expected to play a critical role in achieving the global target of “carbon neutrality” within the next two decades. Potassium‐ion batteries (KIBs), with the advantages of low cost and high operating voltage, and they could become a major component of the required energy‐material ecosystems. Carbon‐based materials have shown promising properties as anode materials for KIBs. However, the key limitation of carbon anodes lies in the dramatic mechanical stress originating from large volume fluctuation during the (de)potassiation processes, which further results in electrode pulverization and rapid fading of cycling performance. Here, a controllable self‐assembly strategy to synthesize uniform dual‐heteroatom doped mesoporous carbon sphere (DMCS) anodes with unique radial pore channels is reported. This approach features a modified Stöber method combined with the single‐micelle template from the molecule‐level precursor design. The DMCS anodes demonstrate exceptional rate capability and ultrahigh cycling stability with no obvious degradation over 12 000 cycles at 2 A g−1, which is one of the most stable anodes. Furthermore, finite element simulations quantitatively verify the stress‐buffering effect of the DMCS anodes. This work provides a strategy from the perspective of stress evolution regulation for buffering mechanical stress originating from large volume fluctuations in advanced KIBs electrodes.

Abstract Background Based on conventional MRI images, it is difficult to differentiatepseudoprogression from true progressionin GBM patients after standard treatment, which isa critical issue associated with survival. The aim of this study was to evaluate the diagnostic performance of machine learning using radiomics modelfrom T1-weighted contrast enhanced imaging(T1CE) in differentiating pseudoprogression from true progression after standard treatment for GBM. Methods Seventy-sevenGBM patients, including 51 with true progression and 26 with pseudoprogression,who underwent standard treatment and T1CE, were retrospectively enrolled.Clinical information, including sex, age, KPS score, resection extent, neurological deficit and mean radiation dose, were also recorded collected for each patient. The whole tumor enhancementwas manually drawn on the T1CE image, and a total of texture 9675 features were extracted and fed to a two-step feature selection scheme. A random forest (RF) classifier was trained to separate the patients by their outcomes.The diagnostic efficacies of the radiomics modeland radiologist assessment were further compared by using theaccuracy (ACC), sensitivity and specificity. Results No clinical features showed statistically significant differences between true progression and pseudoprogression.The radiomic classifier demonstrated ACC, sensitivity, and specificity of 72.78%(95% confidence interval [CI]: 0.45,0.91), 78.36%(95%CI: 0.56,1.00) and 61.33%(95%CI: 0.20,0.82).The accuracy, sensitivity and specificity of three radiologists’ assessment were66.23%(95% CI: 0.55,0.76), 61.50%(95% CI: 0.43,0.78) and 68.62%(95% CI: 0.55,0.80); 55.84%(95% CI: 0.45,0.66),69.25%(95% CI: 0.50,0.84) and 49.13%(95% CI: 0.36,0.62); 55.84%(95% CI: 0.45,0.66), 69.23%(95% CI: 0.50,0.84) and 47.06%(95% CI: 0.34,0.61), respectively. Conclusion T1CE–based radiomics showed better classification performance compared with radiologists’ assessment.The radiomics modelwas promising in differentiating pseudoprogression from true progression.

Abstract Background The medical imaging to differentiate World Health Organization (WHO) grade II (ODG2) from III (ODG3) oligodendrogliomas still remains a challenge. We investigated whether combination of machine leaning with radiomics from conventional T1 contrast-enhanced (T1 CE) and fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) offered superior efficacy. Methods Thirty-six patients with histologically confirmed ODGs underwent T1 CE and 33 of them underwent FLAIR MR examination before any intervention from January 2015 to July 2017 were retrospectively recruited in the current study. The volume of interest (VOI) covering the whole tumor enhancement were manually drawn on the T1 CE and FLAIR slice by slice using ITK-SNAP and a total of 1072 features were extracted from the VOI using 3-D slicer software. Random forest (RF) algorithm was applied to differentiate ODG2 from ODG3 and the efficacy was tested with 5-fold cross validation. The diagnostic efficacy of radiomics-based machine learning and radiologist’s assessment were also compared. Results Nineteen ODG2 and 17 ODG3 were included in this study and ODG3 tended to present with prominent necrosis and nodular/ring-like enhancement (P

The incidence of diffuse large B-cell lymphoma (DLBCL) increases by age and older DLBCL are commonly related to poor prognosis. However, the clinical and biological features of older DLBCL patients remain to be determined. A total of 2,445 patients with newly diagnosed DLBCL were enrolled for clinical data analysis according to age at diagnosis, with tumor samples of 1,150 patients assessed by DNA sequencing and 385 patients by RNA sequencing. Older DLBCL presented advanced disease stage, elevated serum lactate dehydrogenase, poor performance status, multiple extranodal involvement, high percentage of double expressor subtype, and adverse clinical outcome. According to molecular features, age was positively correlated with the oncogenic mutations of PIM1, MYD88, BTG2, CD79B, TET2, BTG1, CREBBP, TBL1XR1, and with the MYD88-like genetic subtype. These oncogenic mutations were involved in B-cell receptor/NF-κB signaling, B-cell differentiation, and histone acetylation based on biological functions. Older DLBCL also manifested reduction in CD4+ naïve T and CD8+ naïve T cells, and also increased recruitment of exhausted T cells and macrophages, leading to immunosuppressive tumor microenvironment. Our work thus contributes to the understanding of aging-related oncogenic mutations and tumor microenvironment alterations in lymphoma progression, and may provide new insights to mechanism-based targeted therapy in DLBCL.

Sequential ultra-small-angle and small-angle and X-ray scattering (USAXS and SAXS) measurements of hierarchical microstructure of a common energetic material, the high explosive 2,4,6-Triamino-1,3,5-trinitrobenzene (TATB), were performed to follow the microstructure evolution upon applied pressure. The pellets were prepared by two different routes—die pressed from a nanoparticle form and a nano-network form of TATB powder. The derived structural parameters, such as void size, porosity, and the interface area, reflected the response of TATB under compaction. Three populations of voids were observed in the probed q range from 0.007 to 7 nm−1. The inter-granular voids with size larger than 50 nm were sensitive to low pressures and had a smooth interface with the TATB matrix. The inter-granular voids with size of ~10 nm exhibited a less volume-filling ratio at high pressures (>15 kN) as indicated by a decrease of the volume fractal exponent. The response of these structural parameters to external pressures implied that the main densification mechanisms under die compaction were the flow, fracture, and plastic deformation of the TATB granules. Compared to the nanoparticle TATB, the applied pressure strongly influenced the nano-network TATB due to its more uniform structure. The findings and research methods of this work provide insights into the structural evolution of TATB during densification.

Relaxation mechanisms of shake gels (particle-polymer systems) are not yet fully understood, mainly because of the lack of effective structural parameters to describe relaxation processes. Small-angle X-ray scattering and dynamic light scattering methods were employed to track the relaxation processes in a water-based shake gel system, composed of 20 wt % of 24.8 nm silica nanoparticles and 0.3 wt % of poly(ethylene oxide) (PEO1000k). The gelation of the studied silica-PEO dispersion was readily induced by quick manual shaking (∼3 cycles/s). Temporal structural evolution of the shake gel after manual agitation was inferred from the development of the modeled parameters. The quantitative structural parameters extracted from the scattering data, i.e. nearest neighbor distance of silica nanoparticles and floc size of gel network, showed that the shake gel network quickly relaxes during the first 10–20 min following the shake-induced gelation, and then slowly reaches a quiescent structure after 1 h.

Dengue has become a huge global health burden. It is currently recognized as the most rapidly spreading mosquito-borne viral disease. Yet, there are currently no licensed vaccines or specific therapeutics to manage the virus, thus, scaling up vector control approaches is important in controlling this viral spread. This study aimed to identify and study in silico, potential anti-mosquito compounds targeting Juvenile hormone (JH) mediated pathways via the Mosquito Juvenile Hormone Binding Protein (MJHBP). The study was implemented using series of computational methods. The query compounds included pyrethroids and those derived from ZINC and ANPDB databases using a simple pharmacophore model in Molecular Operating Environment (MOE). Molecular docking of selected compounds’ library was implemented in MOE. The resultant high-score compounds were further validated by molecular dynamics simulation via Maestro 12.3 module and the respective Prime/Molecular Mechanics Generalized Born Surface Area (Prime/MM-GBSA) binding energies computed. The study identified compounds-pyrethroids, natural and synthetic - with high docking energy scores (ranging from 10.91–12.34 kcal/mol). On further analysis of the high-ranking (in terms of docking scores) compounds using MD simulation, the compounds - Ekeberin D4, Maesanin, Silafluofen and ZINC16919139- revealed very low binding energies (−122.99, −72.91 -104.50 and,-74.94 kcal/mol respectively), fairly stable complex and interesting interaction with JH-binding site amino acid residues on MJHBP. Further studies can explore these compounds in vitro/in vivo in the search for more efficient mosquito vector control.

Melatonin plays key roles in improving fruit quality and yield by regulating various aspects of plant growth. However, the effects of how melatonin regulates primary and secondary metabolites during fruit growth and development are poorly understood. In this study, the surfaces of tomato fruit were sprayed with different concentrations of melatonin (0, 50, and 100 µmol·L−1) on the 20th day after anthesis; we used high-performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometry (LC/MS) to determine the changes in primary and secondary metabolite contents during fruit development and measured the activity of sucrose metabolizing enzymes during fruit development. Our results showed that 100 µmol·L−1 melatonin significantly promoted the accumulation of soluble sugar in tomato fruit by increasing the activities of sucrose synthase (SS), sucrose phosphate synthase (SPS), and acid convertase (AI). The application of 100 µmol·L−1 melatonin also increased the contents of ten amino acids in tomato fruit as well as decreased the contents of organic acids. In addition, 100 µmol·L−1 melatonin application also increased the accumulation of some secondary metabolites, such as six phenolic acids, three flavonoids, and volatile substances (including alcohols, aldehydes, and ketones). In conclusion, melatonin application improves the internal nutritional and flavor quality of tomato fruit by regulating the accumulation of primary and secondary metabolites during tomato fruit ripening. In the future, we need to further understand the molecular mechanism of melatonin in tomato fruit to lay a solid foundation for quality improvement breeding.

Summary: Electrocatalysis-assisted entrapment of polysulfide while ensuring efficient nucleation of Na2S holds the key to addressing the shuttle effect and sluggish kinetics of polysulfide in room-temperature (RT) Na/S batteries. The constrained active sites, however, dramatically limit the efficiency of electrocatalysts. Here, a strategy of electrochemically releasing nano-silver catalytic sites during the discharge process is presented, visualized, and implemented for accelerated Na2S nucleation. Because of the effective polysulfide immobilization and accelerated Na2S nucleation, the sulfur cathode, supported by a self-released silver electrocatalyst, exhibits a superior reversible capacity of 701 mAh g−1 at 0.1 A g−1 and an ultra-stable cycling performance. Precise understanding of the electrochemically self-releasing mechanism and the catalysis in Na2S nucleation via in situ transmission electron microscopy (TEM) would aid, however, in fundamentally optimizing the working mechanism and for further development of more stable high-power RT Na/S batteries.

Migraine is a primary neuropsychological disorder, although its etiology and pathogenesis are unknown. It has been reported that using contingent negative variation, the periodicity of migraine attacks is three days in adults. However, there is still a lack of relevant reports about the periodicity of migraine without aura in adults. Therefore, we investigated the changes of contingent negative variation in adults with migraine without aura from three to seven days after migraine attacks in order to provide the basis for exploring the circulation periodicity of migraine without aura. This prospective, observational study involved a group of 34 individuals with migraine without aura, who were screened during the three to seven days after a migraine attack without aura. A healthy group (31 individuals) was used as controls to assess the amplitudes of contingent negative variation and habituation of early contingent negative variation. Indices of the amplitudes included overall contingent negative variation, initial contingent negative variation, terminal contingent negative variation, and postoperative negative contingent variation. Differences between these indicators were analyzed. No significant difference was found between the patient and control groups for either the amplitudes of these measures of contingent negative variation or habituation of the early contingent negative variation for three to seven days after a migraine attack without aura (all P > 0.05). Thus, the study reported here found that the periodicity of migraine attacks without aura in adults is more than three days.

Abstract Background Several studies have suggested that migraineurs suffer from neurocognitive abnormalities, but this phenomenon and exact mechanisms remain controversial. In this study, we aimed to reevaluate visual spatial attention via event-related potential (ERP) examinations and explore further correlations between ERP data and migraine characteristics. Methods Altogether, 25 migraine patients (9 males, 16 females; mean age 35.240 years) in the interictal period and 21 age-matched healthy controls (8 males, 13 females; mean age 35.286 years) were recruited. A modified visual oddball paradigm which contained standard, target and novel stimuli was used in the test, and amplitudes and latencies of corresponding original/difference ERP components were measured and analyzed independently. Results We found that P3 amplitude was markedly reduced in migraineurs. This phenomenon was further validated in analysis of difference P3 components (target minus standard and novel minus standard). Additionally, the N1 and N2 latencies elicited by novel stimulus were both delayed in patients compared with controls. Furthermore, these deviant cognitive ERPs were correlated with frequency and duration of migraine attacks. Conclusions These results indicated impaired visual spatial attention in migraine patients, which could be related to frequency and duration of attacks.

Resonant walking with preferred gait features is a self-optimized consequence of long-term human locomotion. Minimal energy expenditure can be achieved in this resonant condition. This unpowered multi-joint soft exoskeleton is designed to test whether: (1) there is an obvious improvement in preferred speed and other gait features; (2) resonant walking still exists with exoskeleton assistance. Healthy participants (N = 7) were asked to perform the following trials: (1) walking at 1.25 m/s without assistance (normal condition); (2) walking at 1.25 m/s with assistance (general condition); (3) walking at preferred speed with assistance (preferred condition); (4) walking at the speed in trial (3) without assistance (comparison condition). Participants walked at the preferred frequency and ±10% of it. An average 21% increase in preferred speed was observed. The U-shaped oxygen consumption and lower limb muscle activity curve with the minimum at preferred frequency indicated that the resonant condition existed under the preferred condition. Average metabolic reductions of 4.53% and 7.65% were found in the preferred condition compared to the general and comparison condition, respectively. These results demonstrate that the resonant condition in assisted walking could benefit energy expenditure and provide a new perspective for exoskeleton design and evaluation.

Understanding and solving the psychological health problems of college students have become a focus of social attention. Complex networks have become important tools to study the factors affecting psychological health, and the Gaussian graphical model is often used to estimate psychological networks. However, previous studies leave some gaps to overcome, including the following aspects. (1) When studying networks of subpopulations, the estimation neglects the intrinsic relationships among subpopulations, leading to a large difference between the estimated network and the real network. (2) Because of the high cost, previous psychological surveys often have a small sample size, and the psychological description is insufficient. Here, the intrinsic connections among multiple tasks are used, and multitask machine learning is applied to develop a multitask Gaussian graphical model. The psychological networks of the population and subpopulations are estimated based on psychological questionnaire data. This study is the first to apply a psychological network to such a large-scale college student psychological analysis, and we obtain some interesting results. The model presented here is a dynamic model based on complex networks which predicts individual behavior and provides insight into the intrinsic links among various symptoms.

As a leading cause of vision impairment of the retina, macular edema (ME) has one of the highest clinical demands for treatment. Current treatment of ME relies heavily on invasive techniques resulting in complications and poor patient compliance. To enhance the efficiency of triamcinolone acetonide as eye drop to the posterior segment of the eye, we developed and characterized a novel formulation, namely, triamcinolone acetonide chitosan-coated liposomes (TA-CHL), prepared by the calcium acetate gradient method with some modifications. TA-CHL provided the mean particle size of 135.46 ± 4.49 nm and high entrapment efficiency (90.66 ± 3.21%), exhibited a sustained release profile, excellent physical stability, and no significant toxicity on cornea, conjunctiva, and retina. Optical coherence tomography system (OCT) was used to detect pharmacokinetics of CHL in vivo, indicating that CHL had good potency for drug delivery. Cellular uptake experiments showed CHL had the higher transduction efficiency into HCEC and ARPE-19 than liposomes. TA-CHL was shown to be potentially effective eye drop to contribute to the posterior segment of the eye.

BackgroundTo compare the efficacies of univariate and radiomics analyses of amide proton transfer weighted (APTW) imaging in predicting isocitrate dehydrogenase 1 (IDH1) mutation of grade II/III gliomas.MethodsFifty-nine grade II/III glioma patients with known IDH1 mutation status were prospectively included (IDH1 wild type, 16; IDH1 mutation, 43). A total of 1044 quantitative radiomics features were extracted from APTW images. The efficacies of univariate and radiomics analyses in predicting IDH1 mutation were compared. Feature values were compared between two groups with independent t-test and receiver operating characteristic (ROC) analysis was applied to evaluate the predicting efficacy of each feature. Cases were randomly assigned to either the training (n = 49) or test cohort (n = 10) for the radiomics analysis. Support vector machine with recursive feature elimination (SVM-RFE) was adopted to select the optimal feature subset. The adverse impact of the imbalance dataset in the training cohort was solved by synthetic minority oversampling technique (SMOTE). Subsequently, the performance of SVM model was assessed on both training and test cohort.ResultsAs for univariate analysis, 18 features were significantly different between IDH1 wild-type and mutant groups (P < 0.05). Among these parameters, High Gray Level Run Emphasis All Direction offset 8 SD achieved the biggest area under the curve (AUC) (0.769) with the accuracy of 0.799. As for radiomics analysis, SVM model was established using 19 features selected with SVM-RFE. The AUC and accuracy for IDH1 mutation on training set were 0.892 and 0.952, while on the testing set were 0.7 and 0.84, respectively.ConclusionRadiomics strategy based on APT image features is potentially useful for preoperative estimating IDH1 mutation status.

Summary: T helper 17 (Th17) cell development is programmed by the orphan nuclear receptor RORγt, but the underlying mechanism is not well understood. Nuclear receptor-mediated transcriptional activation depends on coactivators. Here, we show that steroid receptor coactivator-3 (SRC-3) critically regulates Th17 cell differentiation. Reduced incidence of experimental autoimmune encephalitis (EAE) associated with decreased Th17 cell generation in vivo was observed in mice with SRC-3 deletion specifically in T cells. In vitro, SRC-3 deficiency did not affect TGF-β/IL-6-induced Th17 cell generation but severely impaired pathogenic Th17 differentiation induced by IL-1/IL-6/IL-23. Microarray analysis revealed that SRC-3 not only regulates IL-17A but also IL-1R1 expression. SRC-3 bound to Il17a and Il1r1 loci in a RORγt-dependent manner and was required for recruitment of the p300 acetyltransferase. Thus, SRC-3 is critical for RORγt-dependent gene expression in Th17 cell-driven autoimmune diseases. : The unique transcriptional programs in IL-1-induced inflammatory Th17 cells have remained unclear. Tanaka et al. demonstrate that SRC-3 in CD4+ T helper cells functions as a specific coactivator of RORγt, a master transcription factor of Th17 cells, by regulating IL-1-IL1R1 signaling. Keywords: steroid receptor coactivator-3, pathogenic Th17, RORγt, EAE, IL1R1, IL17A, p300

Abstract Background The methylation status of oxygen 6-methylguanine-DNA methyltransferase (MGMT) promoter has been associated with treatment response in glioblastoma(GBM). Using pre-operative MRI techniques to predict MGMT promoter methylation status remains inconclusive. In this study, we investigated the value of features from structural and advanced imagings in predicting the methylation of MGMT promoter in primary glioblastoma patients. Methods Ninety-two pathologically confirmed primary glioblastoma patients underwent preoperative structural MR imagings and the efficacy of structural image features were qualitatively analyzed using Fisher’s exact test. In addition, 77 of the 92 patients underwent additional advanced MRI scans including diffusion-weighted (DWI) and 3-diminsional pseudo-continuous arterial spin labeling (3D pCASL) imaging. Apparent diffusion coefficient (ADC) and relative cerebral blood flow (rCBF) values within the manually drawn region-of-interest (ROI) were calculated and compared using independent sample t test for their efficacies in predicting MGMT promoter methylation. Receiver operating characteristic curve (ROC) analysis was used to investigate the predicting efficacy with the area under the curve (AUC) and cross validations. Multiple-variable logistic regression model was employed to evaluate the predicting performance of multiple variables. Results MGMT promoter methylation was associated with tumor location and necrosis (P

Human gut microbiota play an essential role in both healthy and diseased states of humans. In the past decade, the interactions between microorganisms and tumors have attracted much attention in the efforts to understand various features of the complex microbial communities, as well as the possible mechanisms through which the microbiota are involved in cancer prevention, carcinogenesis, and anti-cancer therapy. A large number of studies have indicated that microbial dysbiosis contributes to cancer susceptibility via multiple pathways. Further studies have suggested that the microbiota and their associated metabolites are not only closely related to carcinogenesis by inducing inflammation and immune dysregulation, which lead to genetic instability, but also interfere with the pharmacodynamics of anticancer agents. In this article, we mainly reviewed the influence of gut microbiota on cancers in the gastrointestinal (GI) tract (including esophageal, gastric, colorectal, liver, and pancreatic cancers) and the regulation of microbiota by diet, prebiotics, probiotics, synbiotics, antibiotics, or the Traditional Chinese Medicine. We also proposed some new strategies in the prevention and treatment of GI cancers that could be explored in the future. We hope that this review could provide a comprehensive overview of the studies on the interactions between the gut microbiota and GI cancers, which are likely to yield translational opportunities to reduce cancer morbidity and mortality by improving prevention, diagnosis, and treatment. Keywords: Inflammation, Immune regulation, Microbial metabolites, Carcinogenesis, Traditional Chinese Medicine

Identification of community structures and the underlying semantic characteristics of communities are essential tasks in complex network analysis. However, most methods proposed so far are typically only applicable to assortative community structures, that is, more links within communities and fewer links between different communities, which ignore the rich diversity of community regularities in real networks. In addition, the node attributes that provide rich semantics information of communities and networks can facilitate in-depth community detection of structural information. In this paper, we propose a novel unified Bayesian generative model to detect generalized communities and provide semantic descriptions simultaneously by combining network topology and node attributes. The proposed model is composed of two closely correlated parts by a transition matrix; we first apply the concept of a mixture model to describe network regularities and then adjust the classic Latent Dirichlet Allocation (LDA) topic model to identify community semantically. Thus, the model can detect broad types of network structure regularities, including assortative structures, disassortative structures, and mixture structures and provide multiple semantic descriptions for the communities. To optimize the objective function of the model, we use an effective Gibbs sampling algorithm. Experiments on a number of synthetic and real networks show that our model has superior performance compared with some baselines on community detection.