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Male cases diagnosed COVID-19 with more complications and higher mortality compared with females, and the overall consequences of male sex hormones and semen parameters deterioration were observed in COVID-19 patients, whereas the involvement and mechanism for spermatogenic cell remains unclear. The study was aimed to investigate the infection mode of S protein (D614G) pseudovirus (pseu-S-D614G) to spermatogenic cells, as well as the influence on cell growth. Both mouse spermatogonia (GC-1 cell, immortalized spermatogonia) and spermatocyte (GC-2 cell, immortalized spermatocytes) were used to detect the infection of pseu-S-D614G of SARS-CoV-2, and further explored the effect of SARS-CoV-2-spike protein (S-protein) and SARS-CoV-2-spike protein (omicron) (O-protein) on GC-1 cell apoptosis and proliferation. The data showed that the pseu-S-D614G invaded into GC-1 cells through either human ACE2 (hACE2) or human CD147 (hCD147), whereas GC-2 cells were insensitive to viral infection. In addition, the apoptosis and proliferation suppression inflicted by S-protein and O-protein on GC-1 cells was through Bax-Caspase3 signaling rather than arresting cell cycle progression. These findings suggest that CD147, apart from ACE2, may be a potential receptor for SARS-CoV-2 infection in testicular tissues, and that the apoptotic effect was induced in spermatogonia cells by S-protein or O-protein, eventually resulted in the damage to male fertility. [ABSTRACT FROM AUTHOR]

The default mode network (DMN) can be subdivided into ventral and dorsal subsystems, which serve affective cognition and mental sense construction, respectively. An internally dissociated pattern of anti-correlations was observed between these two subsystems. Although numerous studies on neuroticism and openness have demonstrated the neurological functions of the DMN, little is known about whether different subsystems and hubs regions within the network are engaged in different functions in response to the two traits. We recruited 223 healthy volunteers in this study and collected their resting-state functional magnetic resonance imaging (fMRI) and NEO Five-Factor Inventory scores. We used independent component analysis (ICA) to obtain the DMN, before further decomposing it into the ventral and dorsal subsystems. Then, the network coherence of hubs regions within subsystems was extracted to construct two structural equation models (SEM) to explore the relationship between neuroticism and openness traits and DMN. We observed that the ventral DMN could significantly predict positive openness and negative neuroticism. The dorsal DMN was diametrically opposed. Additionally, the medial prefrontal cortex (mPFC) and middle temporal gyrus (MTG), both of which are core hubs of the subnetworks within the DMN, are significantly positively correlated with neuroticism and openness. These findings may point to a biological basis that neuroticism and openness are engaged in opposite mechanisms and support the hypothesis about the functional dissociation of the DMN. [ABSTRACT FROM AUTHOR]

This article discusses a case report on the use of bispecific CAR-T cell therapy in a patient with refractory myasthenia gravis (MG), an autoimmune neuromuscular disorder. The patient experienced sustained disappearance of symptoms and anti-acetylcholine receptor antibodies after receiving the therapy. The study suggests that bispecific CAR-T cell therapy has the potential to be an effective treatment for MG and other diseases characterized by autoreactive B cells and autoantibodies. [Extracted from the article]

In the past few years, Transformer-based large language models (LLM) have become the dominant technology in a series of applications. To scale up the sequence length of the Transformer, FlashAttention is proposed to compute exact attention with reduced memory requirements and faster execution. However, implementing the FlashAttention algorithm on the new generation Sunway Supercomputer faces many constraints such as the unique heterogeneous architecture and the limited memory bandwidth. This work proposes SWattention, a highly efficient method for computing the exact attention on the SW26010pro processor. To fully utilize the 6 core groups (CG) and 64 cores per CG on the processor, we design a two-level parallel task partition strategy. Asynchronous memory access is employed to ensure that memory access overlaps with computation. Additionally, a tiling strategy is introduced to determine optimal SRAM block sizes. Compared with the standard attention, SWattention achieves around 2.0x speedup for FP32 training and 2.5x speedup for mixed-precision training. The sequence lengths range from 1k to 8k and scale up to 16k without being out of memory. As for the end-to-end performance, SWattention achieves up to 1.26x speedup for training GPT-style models, which demonstrates that SWattention enables longer sequence length for LLM training. [ABSTRACT FROM AUTHOR]

In this work, nano-levodopa-liposomes (L-dopa-Lip) suspension was prepared by rotary-evaporated film-ultrasonic method, and freeze-drying powders of L-dopa-Lip were also obtained to improve the stability. The products were characterized by TEM, DLS, and TG-DSC, and the phase-transition temperature (Tm) and encapsulation efficiency were calculated. The brain-targeting and in vitro release of the drug was also studied. The results showed that L-dopa-Lip were well-formed spherical vesicles, and the sizes were about 100 nm, and the encapsulation efficiency was higher than 90%. The drug release temperature of L-dopa-Lip was 68 °C, and the in vitro release property and mathematical model were also studied. The brain targeting of L-dopa-Lip in vivo was explored by injecting the gold nanoparticles (AuNPs) labeled L-dopa-Lip (AuNPs-L-dopa-Lip) through the tail vein. ICP-MS and TEM showed that L-dopa-Lip had brain targeting, suggesting the potential treatment of L-dopa-Lip on brain dysfunction. The results of this work might be helpful for designing drug-loaded liposomes for the treatment of central nervous system (CNS) diseases and monitoring their distributions in vivo. [ABSTRACT FROM AUTHOR]

The response of soil microorganisms and plants in soil ecosystems to biochar is well recognised. However, biochars' impact on large soil animal, such as ants, is inadequately understood, with only limited studies focusing on the abundance and mortality rates of some specific ant species. In this study, soil physicochemical properties, and ant community diversity and functional characteristics were compared between experimental plots with and without biochar application. No significant differences in soil (soil physicochemical properties) or ants (ant community richness, species abundance, and morphological characteristics) were observed between the two plots before biochar application. However, the biochar-treated plot soil surface temperatures, pH, and soil water content were significantly higher after 48 weeks. Biochar application promoted Cardiocondyla nuda (by 426%) and Formica japonica abundance (by 93%), but decreased Solenopsis invicta invasive ant species richness (by 54%), consistent with the fact that changes in soil properties were more beneficial to the former two species. In addition, in biochar-treated plots, F. japonica and S. invicta generally showed larger body size (18% and 6.7%), larger eyes (2.7% and 4.0%), and longer femurs (6.3% and 7.9%), which enabled them to respond better to potential barriers, such as plants. Our results highlighted that, besides species abundance and community structure, certain ant functional morphological indicators were also informative in evaluating biochar ecological implications. Highlights: Biochar application enhanced soil temperature, pH, and water content. Ants showed larger body size, larger eyes, and longer femurs with biochar application. Biochar promoted ant richness by creating ant-preferred habitats. [ABSTRACT FROM AUTHOR]

Heritage buildings represent history and act as vessels of human civilisation. The significance of these architectural phenomena increases as society increases, which renders their preservation and ethical use increasingly crucial. Hence, preserving heritage buildings is necessary for societal benefit. The accuracy of three-dimensional (3D) point cloud models of heritage buildings is important to their digital conservation. Traditional mapping methods typically require more time and human resources. Furthermore, the outcome is subject to measurement omissions, errors, and other issues, which are contrary to the protection of the object measured. The complex elements of ancient Chinese architecture render it challenging for traditional measuring techniques to accurately capture spatial structural information. The 3D laser scanning technology is a novel technology to obtain 3D data rapidly. In this paper, the Great Achievement Palace of the Confucian Temple in Yuci District, Jinzhong City, Shanxi Province, was used as an example to examine the application of 3D laser scanning technology to acquire point cloud models of heritage buildings. Field data collection for architectural heritage using 3D laser scanning technology requires measuring station setting analysis to ensure effect accuracy while considering the elements of target location and quantity. For the 3D point cloud model of the Great Achievement Palace, error analysis and accuracy assessment were conducted on the quality elements of alignment accuracy between scanning stations, point cloud model reliability, point cloud data noise condition, and whether the point cloud data were stratified. The findings demonstrated that the improved method quickly and accurately acquired 3D point cloud model data and obtained realistic spatial data models of the heritage building. [ABSTRACT FROM AUTHOR]

The stink bug Arma custos (Hemiptera: Pentatomidae) is a predatory enemy successfully used for biocontrol of lepidopteran and coleopteran pests in notorious invasive species. In this study, a high-quality chromosome-scale genome assembly of A. custos was achieved through a combination of Illumina sequencing, PacBio HiFi sequencing, and Hi-C scaffolding techniques. The final assembled genome was 969.02 Mb in size, with 935.94 Mb anchored to seven chromosomes, and a scaffold N50 length of 135.75 Mb. This genome comprised 52.78% repetitive elements. The detected complete BUSCO score was 99.34%, indicating its completeness. A total of 13,708 protein-coding genes were predicted in the genome, and 13219 of them were annotated. This genome provides an invaluable resource for further research on various aspects of predatory bugs, such as biology, genetics, and functional genomics. [ABSTRACT FROM AUTHOR]

A Fe/Zr bimetal-organic framework (ZrFe-MOF) is utilized to establish a ratiometric fluorescent aptasensor for the determination of tetrodotoxin (TTX). The multifunctional ZrFe-MOF possesses inherent fluorescence at 445 nm wavelength, peroxidase-mimetic activity, and specific recognition and adsorption capabilities for aptamers, owing to its organic ligand, and Fe and Zr nodes. The peroxidation of o-phenylenediamine (OPD) substrate generates fluorescent 2,3-diaminophenazine (OPDox) at 555 nm wavelength, thus quenching the inherent fluorescence of ZrFe-MOF because of the fluorescence resonance energy transfer (FRET) effect. TTX aptamers, which are absorbed on the material surface without immobilization or fluorescent labeling, inhibit the peroxidase-mimetic activity of ZrFe-MOF. It causes the decreased OPDox fluorescence at 555 nm wavelength and the inverse restoration of ZrFe-MOF fluorescence at 445 nm wavelength. With TTX, the aptamers specifically bind to TTX, triggering rigid complex release from ZrFe-MOF surface and reactivating its peroxidase-mimetic activity. Consequently, the two fluorescence signals exhibit opposite changes. Employing this ratiometric strategy, the determination of TTX is achieved with a detection limit of 0.027 ng/mL and a linear range of 0.05–500 ng/mL. This aptasensor also successfully determines TTX concentrations in puffer fish and clam samples, demonstrating its promising application for monitoring trace TTX in food safety. [ABSTRACT FROM AUTHOR]

Melamine-crosslinked polyimide (MPI) aerogels are promising for diverse applications owing to their economical cost and impressive performance. However, MPI aerogels tend to suffer severe shrink in the processes of preparation and practical applications. Their upgrades, i.e., carbon foam-reinforced polyimide (CF-PI) aerogel composites, therefore were proposed in this study, to address this issue. The structure, thermal insulation of the resultant composites as well as their mechanical strength were characterized. The CF-PI aerogel composites were observed to have low shrinkage (as low as 9.25 vol.%) and low thermal conductivity (21 mW m−1 k−1–34 mW m−1 k−1), indicative of significantly improved shape stability and exceptional thermal insulation capability. Besides, these aerogel composites also performed well in thermal stability, and did not decompose unless the temperature exceeds 400 °C. All these advantages contribute to the broad application prospects of thus aerogel composites in many aspects, such as thermal insulation for high temperatures, and so on. Highlights: The carbon foam-reinforced polyimide (CF-PI) aerogel composites have low shrinkage (as low as 9.25 vol.%). The CF-PI aerogel composites have low thermal conductivity (21 mW m−1 k−1–34 mW m−1 k−1). These aerogel composites also performed well in thermal stability, and did not decompose unless the temperature exceeds 400 °C. Since the foam for reinforcement is three-dimensional and can be cut into any shape as desired, the advantages of these CF-PI aerogel composites not only have shape stability, but also can be customized into specific shapes. [ABSTRACT FROM AUTHOR]

Owing to the distinguished mechanical properties, WC and TiC are important engineering materials used in machining and drilling. However, the hardness of WC and TiC is reduced dramatically under elevated temperatures, which therefore limits their application in high-temperature conditions. To reveal the reason for the decrease in hardness of WC and TiC, with the ultimate goal of designing potential hard materials, the temperature-dependent hardness of WC and TiC is investigated by a dislocation-based model. First, the possible dislocations were determined by generalized stacking fault energy distribution. Second, their temperature-dependent elastic constants were calculated, from which the stability and anisotropy were analyzed. WC and TiC are both stable up to 1500 K. The anisotropy of WC is increased with increasing temperature, while that of TiC is decreased. The anisotropy on different planes was also analyzed. Third, the slip system transformations were analyzed. The stress-dependent activation energy and temperature-dependent critical resolved shear stress of all dislocations decrease with increasing stress or temperature. The slip systems of single crystals and polycrystals are both changed with increasing temperature. The temperature-softening rate and yield strength of polycrystals are both between the minimum and maximum values of individual loading directions. Finally, the hardness of WC and TiC was calculated. They both decrease with increasing temperature. In addition, the influences of dislocation density and strain rate were also analyzed. The hardnesses of WC and TiC polycrystals are both decreased with increasing dislocation density. Up to 300 K, the hardness of WC is almost unchanged with increasing strain rate, while at higher temperature, it is increased with increasing strain rate. The hardness of TiC is increased with increasing strain rate. Our findings provide a vital reference for further research in the high-temperature hardness of transition metal carbides. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the role of cognitive function in the efficacy prediction of selective serotonin reuptake inhibitors (SSRIs) for depression patients and to further the understanding of the relationship between baseline cognitive function and depression trajectory. Methods: This was part of a multicenter study for major depressive disorder. The study included 172 first-episode depression patients and 93 recurrent depression patients who had their cognitive function assessed at baseline and followed up for 8 weeks of SSRI treatment. Results: After constructing a 2-level hierarchical linear model with depression change- and cognitive function-level variables, the processing speed at baseline was the best predictor for the improvement of depression at each follow-up in first-episode patients (G11 = 0.03, P = 0.042). The treatment prediction model slope varied across patients depending on the processing speed scores at baseline. With the receiver operating characteristic curve, the combination of sociodemographic characteristics, sedative hypnotics, baseline 17-item Hamilton Rating Scale for Depression (HAMD17), and cognitive function showed the highest predictive power in major depressive disorder remission, resulting in a classification accuracy of 71.5%, a sensitivity of 82.5%, and a specificity of 55.1% (AUC = 0.713; P < 0.001). Conclusion: Baseline cognitive function could help clinicians to better understand the trajectory of first-episode depression patients during acute treatment with SSRIs. [ABSTRACT FROM AUTHOR]

Context: In this paper, the adsorption characteristics of five sulfonamide antibiotic molecules on carbon nanotubes were investigated using density functional theory (DFT) calculations. The adsorption configurations of different adsorption sites were optimized, and the most stable adsorption configuration of each sulfonamide molecule was determined by adsorption energy comparison, and the relative adsorption stability of five sulfonamide molecules on carbon nanotubes was determined by comparing their adsorption energies, i.e., sulfamethazine > sulfadiazine > sulfamerazine > sulfamethoxazole > sulfanilamide. The electron densities of the adsorption configurations were then calculated to confirm that the adsorption of five sulfonamide drug molecules on carbon nanotubes should be physical adsorption. Moreover, the adsorption energy of five sulfonamide molecules on carbon nanotubes in the aqueous environment was larger than that in the vacuum even though the adsorption process remain to be physical adsorption. The adsorption characteristics of the five sulfonamide molecules in various acid–base environments were finally investigated. In contrast, the adsorption energies of the five drug molecules in acid–base environments were significantly reduced, indicating that carbon nanotubes may need to have a suitable pH range to achieve the optimal adsorption effect when they are used for the treatment of sulfonamide antibiotics. Methods: In this paper, we use density functional theory (DFT) with PBE functional to study the adsorption properties of five sulfonamides on carbon nanotubes. The structural optimization and the calculation of electronic structural properties are carried out by CP2K package (version 7.1), adopting the DZVP-MOLOPT-SR-GTH basis set and Goedeck-Teter-Hutter (GTH) pseudo potential. Grimme's D3 correction is used to during all the calculations to correctly capture the influence of the van der Waals interactions. [ABSTRACT FROM AUTHOR]

Superparamagnetic iron oxide (SPIO) nanoparticles play an important role in mediating precise and effective magnetic neurostimulation and can help overcome limitations related to penetration depth and spatial resolution. However, nanoparticles readily diffuse in vivo, decreasing the spatial resolution and activation efficiency. In this study, we employed a microfluidic means to fabricate injectable microhydrogels encapsulated with SPIO nanoparticles, which significantly improved the stability of nanoparticles, increased the magnetic properties, and reinforced the stimulation effectivity. The fabricated magnetic microhydrogels were highly uniform in size and sphericity, enabling minimally invasive injection into brain tissue. The long-term residency in the cortex up to 22 weeks and the safety of brain tissue were shown using a mouse model. In addition, we quantitatively determined the magneto-mechanical force yielded by only one magnetic microhydrogel using a video-based method. The force was found to be within 7–8 pN under 10 Hz magnetic stimulation by both theoretical simulation and experimental measurement. Lastly, electrophysiological measurement of brain slices showed that the magnetic microhydrogels offer significant advantages in terms of neural activation relative to dissociative SPIO nanoparticles. A universal strategy is thus offered for performing magnetic neuro-stimulation with an improved prospect for biomedical translation. [ABSTRACT FROM AUTHOR]

Objective and design: Staphylococcus aureus (S. aureus) is one of the leading causes of human respiratory tract infections. The function of Staphylococcal protein A (SpA), expressed on the S. aureus bacterial membrane and released in the environment, on human nasal epithelial cells (HNECs) have not been fully elucidated. In this study, we tested the SpA expression in S. aureus from chronic rhinosinusitis patients and investigated the effects of SpA on HNECs inflammation through Interferon Gamma Receptor 1(IFNGR1)/phosphorylated Janus Kinase 2 (p-JAK2) pathway. Methods: RNA profiling was performed to investigate inflammatory activation in a S. aureus chronic rhinosinusitis (CRS) mouse model. SpA release by S. aureus clinical isolates was determined using ELISA. The effect of purified SpA and SpA enriched conditioned media from S. aureus clinical isolates on HNECs cytotoxicity, apoptosis and release of inflammatory cytokines was evaluated using lactate dehydrogenase assays, and flow cytometry. SpA dependent IFNGR1 and p-JAK2 expression were assessed by qPCR, immunofluorescence and western blot in HNECs. Results: 49 genes were significantly induced in S. aureus CRS mice indicative of activation of interferon signaling. SpA release was significantly higher in S. aureus clinical isolates from chronic rhinosinusitis with nasal polyps (CRSwNP) patients. Purified SpA significantly increased IFNGR1 mRNA and protein expression in HNECs. SpA induced cytotoxic effects and induced the release of Interleukin-6 (IL-6) and IL-8 in an IFNGR1 dependent way. Conclusion: SpA induces interferon signaling through activation of the IFNGR1-JAK-2 pathway, which provides an understanding of how S. aureus SpA affects the inflammatory process in the upper airways. [ABSTRACT FROM AUTHOR]

China is one of the largest agricultural countries in the world. In the context of China's efforts to achieve dual carbon goals (carbon peak and carbon neutral), the need for carbon emissions reductions in the agricultural sector cannot be ignored. This study collected 2007 to 2018 data from 30 Chinese provinces and used a difference in differences (DID) model to investigate the relationships between China's leading officials' accountability audit of natural resources policy (LOAANR), agricultural technological progress, and agricultural carbon emissions intensities (CEI). A common trend test, placebo test, PSM-DID, and other test methods were used to verify the reliability of the results. The results show that (1) compared with the non-pilot areas, the policy implementation could significantly reduce CEI; (2) the LOAANR was able to stimulate patented technological progress (ATI) and mechanical technological progress (AMT), but different types of technological progress had different mediation effect sizes; and (3) the policy effects shows obvious regional heterogeneity, manifesting as west > east > central; and the policy effects were more obvious in the non-major grain-producing areas, but had no inhibition effects on the CEI in the major grain-producing areas; compared with low intensity market-based environmental regulation (MER) regions, high-intensity MER regions have stronger LOAANR emission reduction effects. Based on the study findings, policy suggestions are given to reduce agricultural carbon emissions and promote higher quality agricultural development. [ABSTRACT FROM AUTHOR]

In this paper, we propose a scheme for speeding up the generation of steady-state entanglement of two interacting qubits by coupling them with an engineered dissipative ancilla. The coupling strength between the target qubits and the ancilla is tailored by state-based Lyapunov control, which vanishes gradually along with the increasing of the fidelity of steady state. The negativity is adopted to measure the bipartite entanglement, which would not be enhanced by such Lyapunov control. In order to speed up and enhance the bipartite entanglement, we further use the non-vanishing engineered coupling. Numerical simulations indicate that the scheme is robust against the fluctuations of the coupling strength and immune to the system parametric errors. The study shows promising performance of speeding up dissipative generation of quantum states with Lyapunov control. [ABSTRACT FROM AUTHOR]

TaC and HfC are recognized as potential ultra-high temperature ceramics for application in refractories and coating materials. However, the test of mechanical property under high temperature is difficult. In this paper, the mechanical properties of TaC and HfC at high temperature are systematically investigated by density functional theory. The results revealed that their elastic constants, elastic moduli and elastic anisotropy all display a monotonic decreasing trend with increasing temperature, and the anisotropy of TaC is stronger than that of HfC at a given temperature. TaC and HfC both have eight possible dislocations. As the applied shear stress increases, the activation energies and critical resolved shear stress (CRSS) of all dislocations are decreased. As the temperature increases, the CRSS is decreased. Moreover, the yield strength and hardness of TaC and HfC both decreased with the increase of temperature. The hardness decrease from 0 to 400 K is mainly due to the proportion change of the two major dislocations ( 1 / 2 1 1 ¯ 0 0° perfect dislocations and 1 / 6 1 2 ¯ 1 30° partial dislocations). Then the hardness sharply decreases at 400 K, which is attributed to the activation of 1 / 6 11 2 ¯ 90° partial dislocations. The hardness decrease from 500 K is attributed to the CRSS change of 1 / 6 11 2 ¯ 90° partial dislocations and 1 / 6 1 2 ¯ 1 30° partial dislocations. In addition, the influence of strain rate and dislocation density are revealed, which shows that their hardness are both increased with increasing strain rate, while decreased with increasing dislocation density. [ABSTRACT FROM AUTHOR]

Shear transfer performance at interface of steel fiber reinforced concrete (SFRC) is of great importance that many factors influence the shear transfer performance of SFRC such as concrete strength and aggregate interlock, reinforcement dowel action and steel fiber. Many studies have focused on part of the factors. The shear transfer performance of uncracked monolithic SFRC is studied in this paper by considering the combined effects of cohesion, clamping stress, confined stress, reinforcement, and steel fiber. Thus, this study presents a series of direct shear tests by Z-type push-off specimens. The direct shear strength, failure mode and failure process of plain SFRC and reinforced SFRC are studied, and their shear stress-slip and shear stress-crack width responses of the tested specimens are obtained. Test results showed that reinforcement and steel fibers can improve the ductile behavior and shear strength of the shear interface simultaneously. And shear stress-slip and —crack curves of the test specimens with those combined effects are strongly nonlinear. Finally, based on the existing shear strength calculation model and the test results of this paper, a shear transfer calculation formula of SFRC interface is proposed and verified according to the Mohr Coulomb failure criteria. [ABSTRACT FROM AUTHOR]

The concept of treating waste with waste is of great significance to realize the sustainable development of human society. In this work, the high metals-containing coal gasification fine slag (CGFS) from the coal gasification industry is directly transformed into an excellent adsorbent for malachite green wastewater adsorption. CGFS exhibits a rough and porous structure, which is mainly composed of SiO2 and various metal compounds. Numerous spherical structures which are generated by the melting of inorganic substances are distributed on the surface of CGFS with a large number of flocculent carbon structures covering the substrate or interspersed. Experiments confirm that CGFS is a competitive adsorbent for the removal of malachite green due to its low cost and high adsorption performance. The theoretical maximum adsorption capacity of CGFS at 298 K predicted by the Langmuir model reached as high as 1787 mg/g and the capacity increases with the temperature. The removal efficiency reached 100% for CGFS at a solid–liquid ratio of 0.05 g/100 mL and a malachite green concentration of 100 mg/L. A dominant role of chemisorption was confirmed by the analytical results of the pseudo-second-order model and the Freundlich model combined with the characterization results. The metal oxides and carbon structures in CGFS are presumed to be the main active adsorption sites. From the fitting of the intraparticle diffusion model, the adsorption rate was limited first by membrane diffusion and then by intraparticle diffusion as the adsorption process proceeded. [ABSTRACT FROM AUTHOR]

This paper used a dynamic spatial panel model to empirically analyze the effects of environmental regulation, market demand, and the associated spatial spillovers on regional green innovation in China, from which the following was found. (1) The environmental regulations had a positive "U-shaped" effect on local green innovation and a positive neighborhood spillover effect, and market demand had a significant positive effect on local green innovation and a "ripple effect." (2) The mechanism analysis found that the environmental regulations tended to inhibit regional green innovation input through a "cost compliance" effect, and market demand had a stronger incentive effect on innovation input than the environmental regulations, thus promoting the improvement of green innovation level. (3) The environmental regulation and market demand effects on green innovation had obvious spatial and temporal heterogeneity. The results of this study could help to promote regional green innovation by formulating reasonable environmental policies and stimulating the vitality of green technology market. [ABSTRACT FROM AUTHOR]

To directly incorporate the intermolecular interaction effects into the discrete unified gas-kinetic scheme (DUGKS) for simulations of multiphase fluid flow, we developed a pseudopotential-based DUGKS by coupling the pseudopotential model that mimics the intermolecular interaction into DUGKS. Due to the flux reconstruction procedure, additional terms that break the isotropic requirements of the pseudopotential model will be introduced. To eliminate the influences of nonisotropic terms, the expression of equilibrium distribution functions is reformulated in a moment-based form. With the isotropy-preserving parameter appropriately tuned, the nonisotropic effects can be properly canceled out. The fundamental capabilities are validated by the flat interface test and the quiescent droplet test. It has been proved that the proposed pseudopotential-based DUGKS managed to produce and maintain isotropic interfaces. The isotropy-preserving property of pseudopotential-based DUGKS in transient conditions is further confirmed by the spinodal decomposition. Stability superiority of the pseudopotential-based DUGKS over the lattice Boltzmann method is also demonstrated by predicting the coexistence densities complying with the van der Waals equation of state. By directly incorporating the intermolecular interactions, the pseudopotential-based DUGKS offers a mesoscopic perspective of understanding multiphase behaviors, which could help gain fresh insights into multiphase fluid flow. [ABSTRACT FROM AUTHOR]

The predictions of the multiple-regime flows from continuum regime to free molecular regime are crucial for the aerodynamic design in a large number of engineering applications, such as the near-space craft, the ultra-low orbit spacecraft and the micro- electro-mechanical systems (MEMS). Since the essence of this multiple-regime problem is a complex system composed by different scales and mechanics, the modeling and numerical prediction of these multiple-regime flows are very challenging at both theoretical and practical levels. Moreover, the single flow field with multiple flow regimes will make the problem extremly complicated. Unfortunately, this typical flow field is very common in hypersonic application and important for the development of multiple-regime aerodynamics. On the other hand, both the constructions of the low density wind tunnel with high enthalpy and the high altitude flight experiment are also very challenging at the present stage. Therefore, the researches on the multiple- regime flows and the corresponding complex science hit a worldwide bottleneck. This paper reviews the breakthroughs in the computational methods for multiple-regime flows in the last ten years, which can be used as numerical experimental tools for studying the multiple-scale flow mechanism and providing data for aerodynamic designs and thermal protections. This paper focuses on the progress of the unified wave-particle methods established in recent years, which are proved to be both accurate and efficient for multiple-regime flows with extremly high speed. [ABSTRACT FROM AUTHOR]

Schizophrenia which is an abnormally developmental disease has been widely reported to show abnormal brain structure and function. Enhanced functional integration is a predominant neural marker for brain mature. Abnormal development of structure and functional integration may be a biomarker for early diagnosis of schizophrenia. Fifty-five patients with early onset schizophrenia (EOS) and 79 healthy controls were enrolled in this study. Voxel-based morphometry (VBM) and functional connectivity density (FCD) were performed to explore gray matter volume (GMV) lesion, abnormal functional integration, and concurrent structural and functional abnormalities in the brain. Furthermore, the relationships between abnormalities structural and function and clinical characteristics were evaluated in EOS. Compared with healthy controls, EOS showed significantly decreased GMV in the bilateral OFC, frontal, temporal, occipital, parietal and limbic system. EOS also showed decreased FCD in precuneus and increased FCD in cerebellum. Moreover, we found concurrent changes of structure and function in left lateral orbitofrontal cortex (lOFC). Finally, correlation analyses did not find significant correlation between abnormal neural measurements and clinical characteristic in EOS. The results reveal disassociated and bound structural and functional abnormalities patterns in EOS suggesting structural and functional measurements play different roles in delineating the abnormal patterns of EOS. The concurrent structural and functional changes in lOFC may be a biomarker for early diagnosis of schizophrenia. Our findings will deepen our understanding of the pathophysiological mechanisms in EOS. [ABSTRACT FROM AUTHOR]

A dual-readout immunosensor coupled with electrochemical impedance and temperature signal was successfully proposed to detect autoimmune hepatitis markers (ASGPR). Nb2C MXene with excellent conductivity, abundant surface functional groups, and extraordinary photothermal conversion efficiency, was designed to be a multifunctional biological probe, whose specific binding with antigen enhanced steric hindrance to generate electrochemical impedance signal, and at the same time, it had a strong optical response in the near-infrared band to achieve temperature output. In addition, poly(N-isopropyl acrylamide) (PNIPAM) was a temperature-sensitive polymer, which was adopted as the sensing matrix. When the multifunctional probe was specifically bound to the antigen, under 808-nm laser irradiation, the captured Nb2C MXene achieved photothermal conversion to increase the electrode surface temperature, and the conformation of PNIPAM changed from a free spiral to a spherical shape, further realizing double amplification of the EIS signal. Under the optimized experimental conditions, the impedance values and the temperature changes increased proportionally with the increase of the ASGPR concentration from 10−5 to 1 ng/mL, and the detection limit of the immunosensor was 3.3 × 10−6 ng/mL. The established dual-readout immunosensor exhibited good selectivity and acceptable stability and provided an effective detection method for autoimmune hepatitis marker detection. [ABSTRACT FROM AUTHOR]

Under the pressure of environmental crisis caused by production and economic development, a policy for Leading Officials' Accountability Audit of Natural Resources (LOAANR) was issued in 2014 to reduce the environmental risks and gain high-quality economy. Taking LOAANR policy as the research object, and based on 2011 to 2018 panel data from Chinese heavy-polluting enterprises, this paper employed a two-way fixed difference-in-differences (DID) model to explore the relationship between the LOAANR, environmental costs (ECs) and green innovation (GI). It was found that the implementation of the LOAANR significantly promoted enterprise GI, with the regulating impact mechanism, EC. GI efficiency was measured by continuous DID method. A heterogeneity analysis revealed that non-state-owned enterprises (NSOEs) were more eager to environmentally innovate. A corporate life cycle heterogeneity analysis of the GI policy effect found that the policy effect was negative in the decline stages. Compared with the eastern Chinese enterprises, enterprises in other regions were found to be more prone to positively adopting GI to maximize benefits in the face of the LOAANR. The policy was observed to have inhibited GI in central Chinese enterprises. It was also demonstrated that the policy effect has time and regional dynamic effect. Common trend, placebo, PSM-DID tests, and another robustness regressions were applied to support the conclusions. All the findings are expected to provide basic theoretical guidance for more environmental policies and high-quality production. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive cognitive disorder that occurs worldwide, and the lack of disease-modifying targets and pathways is a pressing issue. This study aimed to provide new targets and pathways by performing molecular subgroup classification. After normalizing the collected data, the subgroup number was confirmed with consensus clustering. Comparisons of clinical features among subgroups were conducted to clarify the clinical traits of each subgroup. Subgroup-specific genes were identified to perform weighted gene coexpression analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out. Next, gene set enrichment analysis (GSEA) was performed. Protein–protein interaction networks were built to screen core genes and in each subgroup to perform Spearman correlation analysis with clinical traits. Sequencing profiles of 1068 AD samples collected from 2 datasets were classified into 3 subgroups. Clinical comparisons revealed that patients in subgroup III tended to be younger, while their pathological grades were the most severe. WGCNA detected four gene modules, and the turquoise module, where the dopaminergic synapse pathway was enriched, was related to subgroup I. The neurotrophin signaling pathway and TGF-beta signaling pathway were robustly enriched in the blue and brown modules, respectively, in subgroup III. Moreover, 3 hub genes in subgroup I were negatively correlated with the sum of neurofibrillary tangle (Nft) density. Conversely, hub genes in subgroups II and III exhibited positive correlations with the sum of Nft density. These results provide new pathways and targets for AD treatment. [ABSTRACT FROM AUTHOR]

The present study was designed to assess whether raised Serine protease inhibitor Kazal type 1 (SPINK1) expressions modulates angiogenesis. Human umbilical vein endothelial cells (HUVECs) exposed to SPINK1 were noted to exhibit raised expressions of interleukin-8 (IL-8) as well as VCAM-1 and ICAM-1 cell adhesion molecules in a dose-dependent manner. In co-culture system of HUVECs and Acute lymphoblastic leukemia (ALL) cells, SPINK1 exposure also resulted in enhanced endothelial cell motility and ALL cells trans-endothelial migration. High concentrations of SPINK1 caused in vitro cellular reorganization into tubes in Matrigel-cultured HUVECs and induced in vivo vascularization and brain infiltration of NOD/SCID ALL model mice. The further transcriptomic analysis indicated that SPINK1 treatment altered several biological processes of endothelial cells and led to activation of the MAPK pathway. This study is the first to determine the neovascularization effects of raised SPINK1. [ABSTRACT FROM AUTHOR]

Beta-chitin patch has previously been proven to be an effective haemostat, but whether modifying the patch affects its efficacy and safety, remains unanswered. In this study, the patch was modified using polyethylene oxide, Pluronic-F127, calcium, increased thickness or polyphosphate, and their effect on the process of haemostasis and cytotoxicity was tested and compared with standard-of-care, Surgicel and FloSeal. Whole blood collected from volunteers was applied to the patches to test their whole blood clotting and thrombin generation capacities, whilst platelet isolates were used to test their platelet aggregation ability. The fluid absorption capacity of the patches was tested using simulated body fluid. Cytotoxicity of the patches was tested using AlamarBlue assays and PC12 cells and the results were compared with the standard-of-care. In this study, beta-chitin patch modifications failed to improve its whole blood clotting, platelet aggregation and thrombin generation capacity. Compared to non-modified patch, modifications with polyethylene oxide or calcium reduced platelet aggregation and thrombin generation capacity, while increasing the thickness or adding polyphosphate decreased platelet aggregation capacity. The cytotoxicity assays demonstrated that the beta-chitin patches were non-toxic to cells. In vivo research is required to evaluate the safety and efficacy of the beta-chitin patches in a clinical setting. [ABSTRACT FROM AUTHOR]

A low cost and effective indirect competitive method is reported to detect five EDCs, 17-beta-estradiol (E2), estriol (E3), bisphenol A (BPA), diethylstilbestrol (DES), and nonylphenol (NP) simultaneously, based on suspension array technology (SAT). Five kinds of complete antigens (E2-BSA, E3-BSA, BPA-BSA, DES-BPA, NP-BSA) were coupled to different encoding microspheres using purpose-made solutions in our laboratory instead of commercially available amino coupling kits; the method was further optimized for determination and reducing the cost. Encoding and signaling fluorescence of the particles are determined at 635/532 nm emission wavelengths. High-throughput curves of five EDCs were draw and the limit of detection (LOD) were between 0.0010 ng mL−1 ~ 0.0070 ng mL−1. Compared with traditional ELISA methods, the SAT exhibited better specificity and sensitivity. Experiments using spiked milk and tap water samples were also carried out, and the recovery was between 85 and 110%; the results also confirmed good repeatability and reproducibility. It illustrated great potential of the present strategy in the detection of EDCs in actual samples. [ABSTRACT FROM AUTHOR]

Polyimide (PI) aerogels with crosslinked structure are promising for diverse applications owing to their nano-porous nature and superior properties in many aspects. However, the crosslinkers used for preparing crosslinked PI aerogels are always laboriously available and expensive. The economical melamine therefore was chosen as a substitute in this study. It was proved that the use of melamine was indeed a viable strategy for effectively crosslinking PI chains. The resultant melamine-crosslinked PI (MPI) aerogels were tested to have relatively low shrinkage (as low as 9.96 vol%), ultralight bulk densities (0.084–0.116 g cm−3) and low thermal conductivity (< 40.0 mW m−1 K−1), together with considerable thermal stability (onset temperature to decompose up to 503 ℃) and acceptable compressive strength (Young's modulus of 1.12–10.04 MPa). Meanwhile, the morphology and properties of MPI aerogels can also be tailored by regulating the proportion of hybrid diamines as well as the polymer concentration of pristine solution. Given all of these, MPI aerogels using melamine as an economical yet effective crosslinker will have a broad prospect in many fields including thermal insulation. [ABSTRACT FROM AUTHOR]

Metal-organic frameworks (MOFs) have captured substantial attention of an increasing number of scientists working in sensing analysis fields, due to their large surface area, high porosity, and tunable structure. Recently, MOFs as attractive fluorescence quenchers have been extensively investigated. Given their high quenching efficiency toward the fluorescence intensity of dyes-labeled specific biological recognition molecules, such as nucleic acids, MOFs have been widely developed to switch fluorescence biosensors with low background fluorescence signal. These strategies not only lead to specificity, simplicity, and low cost of biosensors, but also possess advantages such as ultrasensitive, rapid, and multiple detection of switch fluorescence methods. At present, researches of the analysis of switch fluorescence biosensors based on MOFs and nucleic acids mainly focus on sensing of different types of in vitro and intracellular analytes, indicating their increasing potential. In this review, we briefly introduce the principle of switch fluorescence biosensor and the mechanism of fluorescence quenching of MOFs, and mainly discuss and summarize the state-of-the-art advances of MOFs and nucleic acids-based switch fluorescence biosensors over the years 2013 to 2020. Most of them have been proposed to the in vitro detection of different types of analytes, showing their wide scope and applicability, such as deoxyribonucleic acid (DNAs), ribonucleic acid (RNAs), proteins, enzymes, antibiotics, and heavy metal ions. Besides, some of them have also been applied to the bioimaging of intracellular analytes, emerging their potential for biomedical applications, for example, cellular adenosine triphosphate (ATP) and subcellular glutathione (GSH). Finally, the remaining challenges in this sensing field and prospects for future research trends are addressed. [ABSTRACT FROM AUTHOR]

CRISPR/Cas9 system has become a promising gene editing tool for cancer treatment. However, development of a simple and effective nanocarrier to incorporate CRISPR/Cas9 system and chemotherapeutic drugs to concurrently tackle the biological safety and packaging capacity of viral vectors and combine gene editing-chemo for cancer therapy still remains challenges. Herein, a chain-shattering Pt(IV)-backboned polymeric nanoplatform is developed for the delivery of EZH2-targeted CRISPR/Cas9 system (NPCSPt/pEZH2) and synergistic treatment of prostate cancer. The pEZH2/Pt(II) could be effectively triggered to unpack/release from NPCSPt/pEZH2 in a chain-shattering manner in cancer cells. The EZH2 gene disruption efficiency could be achieved up to 32.2% of PC-3 cells in vitro and 21.3% of tumor tissues in vivo, leading to effective suppression of EZH2 protein expression. Moreover, significant H3K27me3 downregulation could occur after EZH2 suppression, resulting in a more permissive chromatin structure that increases the accessibility of released Pt(II) to nuclear DNA for enhanced apoptosis. Taken together, substantial proliferation inhibition of prostate cancer cells and further 85.4% growth repression against subcutaneous xenograft tumor could be achieved. This chain-shattering Pt(IV)-backboned polymeric nanoplatform system not only provides a prospective nanocarrier for CRISPR/Cas9 system delivery, but also broadens the potential of combining gene editing-chemo synergistic cancer therapy. [ABSTRACT FROM AUTHOR]

The Daqingshan area in China located in the center part of the Khondalite belt, north of the Ordos Block and south of the Yinshan Block. The Daqingshan basin is the best-preserved Mesozoic basin that is oriented nearly east-west. Previous studies suggest that the provenance of Jurassic sediment is mainly the Khondalite belt and no material from Yinshan Block. We present detailed data on the detrital-zircon geochronology of the Jurassic sandstones from the Daqingshan area. The detrital-zircon U–Pb age data of the Wudanggou and Changhangou Formations show two peaks at ~2450 Ma and 1970–1930 Ma, with a few of Archean ages. The detrital-zircon age data of the Daqingshan Formation show three distinctive age populations of 2560–2460 Ma, 1950–1750 Ma, and 320–265 Ma. Comparison with the age of the surrounding magmatic rocks suggests that the main source area is the Wulashan–Daqingshan Complex, with the Yinshan Block being a lesser source. However, more Archean and Paleozoic detrital zircon occurs in the Daqingshan Formation, probably as a result of the rise of the western part of the basin and eastward movement of the center of the basin, thereby increasing provenance from the Yinshan Block. The Yanshan movement caused massive amounts of Yinshan material to move southward during the Middle-Late Jurassic. However, the barrier of the Yinshan Mountains caused Yinshan material to be deposited mainly in the eastern part of the basin. [ABSTRACT FROM AUTHOR]

Few studies have reported on brain functional differences between healthy individuals with auditory verbal hallucinations (Hi-AVH) with and without insight, so we designed a study to address this knowledge gap. We enrolled 12 Hi-AVH with insight, 15 Hi-AVH without insight, and 15 AVH-free controls (Healthy controls). Global functional connectivity density (gFCD) mapping was used to estimate brain networks. We found that the most common alterations in both Hi-AVH groups were increased gFCD in superior parietal lobule and superior temporal gyrus. We also found that distinct brain functional patterns of Hi-AVH without insight comprised lower gFCD in the frontal lobe oculomotor area, dorsolateral prefrontal cortex, supramarginal gyrus, primary auditory cortex, sensorimotor cortex, ventral anterior, and posterior cingulate Our pilot findings support the hypothesis that abnormal reciprocal action in the circuits for processing perception, memory, language, and attentional control may be pathological features of auditory verbal hallucinations. [ABSTRACT FROM AUTHOR]

To develop graphene-based composite aerogels with improved compressive shape stability that suitable for high-temperature applications, poly (m-phenylene isophthalamide, PMIA) with excellent heat resistance and flame retardancy was used as the supporting material. The effects of PMIA content on aerogel morphology, structure, mechanical and thermal properties were discussed. Unlike other polymers, PMIA in the composite aerogels appeared as separate or stacked particles instead of interconnected framework or uniform coatings. Higher PMIA content tended to result in denser aerogels with smaller pores and thinner graphene sheet walls. The densified structure with plenty of PMIA particles incorporated was found to make the aerogel more rigid and less flexible. Their compressive strength therefore was greatly enhanced. Besides, it was also observed that the thermal conductivity of the prepared aerogels increased with the increase of PMIA content. Nevertheless, their thermal conductivity was still <0.045 W m−1 K−1, indicative of considerable thermal insulation ability. Given that, the prepared composite aerogels with enhanced compressive shape stability may have a broad application prospect in thermal insulation. Highlights: PMIA-reinforced graphene aerogels (PGAs) are successfully prepared by a premixing method. The resulted PGAs have smaller pores and thinner graphene walls with numerous PMIA particles incorporated. PGAs can support >2000 times its own weight, indicative of enhanced compressive strength. PGAs are good at thermal insulation with thermal conductivity values <0.045 W m−1 K−1. [ABSTRACT FROM AUTHOR]

Background and aims: Endoscopic full-thickness resection (EFTR) has been increasingly applied in the treatment of gastric submucosal tumors (G-SMTs) with explorative intention. This study aimed to compare the efficacy, tolerability, and clinical outcomes of EFTR and surgical intervention for the management of muscularis propria (MP)-derived G-SMTs. Methods: Between September 2011 and May 2019, the clinical records of patients with MP-derived G-SMTs undergoing EFTR at our endoscopic unit were collected. A cohort of people with primary MP-derived G-SMTs treated by surgery was matched in a 1:1 ratio to EFTR group with regard to patients' baseline characteristics, clinicopathologic features of the tumor and the procedure date. The perioperative outcomes and follow-up data were analyzed. Results: In total, 62 and 62 patients were enrolled into the surgery and EFTR group, respectively, with median follow-up of 786 days. The size of G-SMTs (with ulceration) ranged from 10 to 90 mm. For patients with tumor smaller than 30 mm, surgery and EFTR group presented comparable procedural success rate (both were 100%), en bloc resection rate (100% vs. 94.7%), tumor capsule rupture rate (0% vs. 5.3%), and pathological R0 resection rate (both were 100%). EFTR had a statistically significant advantage over surgery for estimated blood loss (3.12 ± 5.20 vs. 46.97 ± 60.73 ml, p ≤ 0.001), discrepancy between the pre- and postprocedural hemoglobin level (5.18 ± 5.43 vs. 9.84 ± 8.25 g/L, p = 0.005), bowel function restoration [1 (0–5) vs. 3 (1–5) days, p ≤ 0.001], and hospital cost (28,617.09 ± 6720.78 vs. 33,963.10 ± 13,454.52 Yuan, p = 0.033). The patients with tumor larger than 30 mm showed roughly the same outcomes after comparison analysis of the two groups. However, the clinical data revealed lower en bloc resection rate (75.0% vs. 100%, p = 0.022) and higher tumor capsule rupture rate (25.0% vs. 0%, p = 0.022) for EFTR when compared to surgery. The procedure time, duration of postprocedural fasting and antibiotics usage, and hospital stay of the two groups were equivalent. The occurrence rate of adverse events within postoperative day 7 were 74.2% and 72.6% after EFTR and surgery, respectively (p = 1.000). No complications occurred during the follow-up. Conclusion: For treatment of MP-derived G-SMTs (with or without ulceration), our study showed the feasibility and safety of EFTR, which also provided better results in terms of procedural blood loss, the postoperative bowel function restoration and cost-effectiveness when compared to surgery, whereas the surgery was superior in en bloc resection rate for G-SMTs larger than 30 mm. The postprocedural clinical outcomes seemed to be equivalent in these two resection methods. [ABSTRACT FROM AUTHOR]

A new isocoumarin compound named setosphacohol A (1), together with six known ones, alternariol (2), isoaltenuene (3), phomasatin (4), alternariol 5-O-methyl ether (5), 1-deoxyrubralactone (6), and rubralactone (7), was isolated from the entomogenous fungus Setosphaeria sp. The structure of the new compound was elucidated by analysis of the 1D and 2D spectroscopic data as well as MS. Compounds 2, 5, 6 showed moderate cytotoxicity against six human tumor cell lines MCF-7, MGC-803, H1975, Huh-7, A549, and HeLa with IC50 values ranging from 23.04 to 96.91 μg·mL–1. [ABSTRACT FROM AUTHOR]

Energy loss within organic solar cells (OSCs) is undesirable as it reduces cell efficiency1–4. In particular, non-radiative recombination loss3 and energetic disorder5, which are closely related to the tail states below the band edge and the overall photon energy loss, need to be minimized to improve cell performance. Here, we report how the use of a small-molecule acceptor with torsion-free molecular conformation can achieve a very low degree of energetic disorder and mitigate energy loss in OSCs. The resulting single-junction OSC has an energy loss due to non-radiative recombination of just 0.17 eV and a high power conversion efficiency of up to 16.54% (certified as 15.89% by the National Renewable Energy Laboratory). The findings take studies of organic photovoltaics deeper into a new regime, beyond the limits of energetic disorder and large energy offset for charge generation. An organic solar cell designed with minimal energetic disorder exhibits very low energy loss due to non-radiative recombination and highly efficient operation. [ABSTRACT FROM AUTHOR]

Major psychiatric traits are genetically inter-correlated with one another, but it not well known which genes play pleiotropic effects across different traits. We curated and compared genes identified from large-scale genome-wide association studies for seven psychiatric traits, including depression, bipolar disorder, schizophrenia, autism spectrum disorder, attention-deficit/hyperactivity disorder, anxiety and neuroticism. We then explored biological functions of the top pleiotropic genes. A total of 243 cross-trait genes were identified for the seven traits. Except for autism spectrum disorder, there was significant enrichment of overlapped genes across these psychiatric traits. Chromosome 5q14.3, 11q23.2, and 7p22.3 are the three genomic regions conferring highest pleiotropic effects for these psychiatric traits. The long non-coding gene LINC00461 showed the highest pleiotropic effects on five psychiatric traits. In silico and functional studies with mice support the vital role of LINC00461 in neurodevelopment. In sum, our study provides insights into the shared genetic liability among major psychiatric traits. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) gene is frequently mutated in non-small cell lung cancer (NSCLC), which can be targeted by EGFR tyrosine kinase inhibitors (TKIs). It is hard, however, to monitor the performance of EGFR-TKI therapy dynamically. Therefore, therapeutic indicators are urgently needed. Novel antibody microarray, containing 41,472 antibodies, was used for comprehensive analyzing of serum samples from 9 normal subjects and 9 EGFR mutated lung adenocarcinoma patients at three EGFR-TKI treatment time points, including before treatment (Baseline), partial response (PR) during treatment, and disease progression (PD) after resistance. Through microarray data analysis, five candidate antibodies were screened out for confirmation in serum samples and the verified one was utilized for candidate protein identification through immunoprecipitation-mass spectrometry strategy. A novel protein, isoform 2 of fibrinogen alpha chain (FGA2), was revealed and verified in the discovery sample set. Its performance as therapy indicator was further evaluated in another pre-validation sample set (n = 60). Our data confirmed that serum FGA2 level was correlated with EGFR-TKI response (p < 0.05). The expression and secretion of FGA2 in hepatocytes were inhibited by EGFR-TKI, partially explaining the downregulation of FGA2 in serum. Our results demonstrate that FGA2 is an indicator of targeted therapy for EGFR mutated lung adenocarcinoma. Key messages: Antibody microarray was coupled with mass spectrometry for proteomics research. FGA2 was discovered as an indicator of EGFR-TKI targeted therapy. FGA2's expression/secretion in hepatocytes was dramatically inhibited by EGFR-TKI. [ABSTRACT FROM AUTHOR]

Three kinds of hypereutectic Fe–Cr–C hardfacing coatings were designed to research the refinement effect and heterogeneous nucleation mechanism of NbC on nano-Y2O3 in the coatings. The microstructure and elemental maps of Fe–Cr–C–Nb–Y2O3 coating were investigated by field emission scanning electron microscope. The phase structures of the coating and heterogeneous nucleation were researched by transmission electron microscope (TEM). The lattice mismatch between Y2O3 and NbC was computed by Bramfitt's two-dimensional lattice mismatch theory. The adhesive strength, interface energy and electronic properties of Y2O3(111)/NbC(110) interfaces were calculated by a first-principles method. The bonding characteristics of heterogeneous nucleation interfaces were analyzed by charge density difference, electron localization function and Bader charge population. The experimental results show that the primary M7C3 can be refined by NbC, when Nb additive was added into the Fe–Cr–C coating. When nano-Y2O3 and Nb additive were added into the coating simultaneously, the primary M7C3 can be further refined. The SEM results show that NbC can be effective heterogeneous nucleation substrate of the primary M7C3 and there is a compound containing rare earth (RE) element Y in NbC particle. The TEM results verified the RE compound in NbC particle is Y2O3, and they combine together tightly. The calculation results indicate that the two-dimensional lattice mismatch of Y2O3(111)/NbC(110) interface is 6.8%, which reveals that Y2O3 meets the geometric condition to act as a medium-effective heterogeneous nucleation substrate of NbC. In all interface models, the adhesive strength of O-Bridge model is the largest (Wad = 9.75 J/m2) and its stability is the best (γ = − 0.87 J/m2). The major bond type of O-terminated interfaces is covalent one. Actually, the interfacial energy of O-terminated interface is negative, which reveals that their formation process is a process of energy reduction and structure stabilization. It means Y2O3 and NbC can form stable interface structure. It can be predicted that the heterogeneous nucleation occurs preferably on the O-terminated interfaces. Therefore, Y2O3 can serve as an effective heterogeneous nucleation substrate of NbC to refine it. [ABSTRACT FROM AUTHOR]

Fetal growth has been demonstrated to be an important predictor of perinatal and postnatal health. Although the effects of maternal exposure to air pollution during pregnancy on fetal growth have been investigated using ultrasound in many previous studies, the results were inconsistent and disputable. We aimed to qualitatively and quantitatively investigate the associations of air pollution exposure during different periods of pregnancy with fetal growth and anthropometric measurements at birth. We searched for all studies investigating the associations of air pollution exposure during pregnancy with fetal growth and birth anthropometric measurements in English and Chinese databases published before July 31, 2017. A random-effects model was employed in the meta-analysis to estimate the pooled effects of each 10 μg/m3 increment in air pollutant exposure. The ACROBAT-NRSI tool was applied to assess the quality of each included study, and the GRADE tool was employed to assess the overall quality of the meta-analysis. Maternal PM2.5 exposure (10 μg/m3) during the entire pregnancy was negatively associated with head circumference at birth (β = − 0.30 cm, 95% CI − 0.49, − 0.10), and NO2 exposure during the entire pregnancy was significantly linked to shorter length at birth (β = − 0.03 cm, 95% CI − 0.05, − 0.02). Maternal exposure to higher NO2 and PM2.5 during pregnancy may impair neonatal head circumference and length development, respectively. More studies are needed to confirm the effects of NO2 and PM2.5 and to identify the sources and major toxic components of PMs. [ABSTRACT FROM AUTHOR]

The present paper describes a novel two-dimensional liquid chromatography (2D-LC) system, which is comprised of a first-dimensional ion exchange chromatography (IEX1) column, trap column, and second-dimensional reversed-phase chromatography (RP2) column system. The biological sample is separated by the first-dimensional LC using an IEX column to remove interferences. The analytes are transferred to the trap column after heart-cutting. Then, the analytes are transferred to the second-dimensional LC using an RP2 column for further separation and ultraviolet detection. This 2D-LC system can offer a large injection volume to provide sufficient sensitivity and exhibits a strong capacity for removing interferences. Here, the determination of three monoterpene indole alkaloids (MIAs; gelsemine, koumine, and humantenmine) from Gelsemium in biological matrices (plasma, tissue, and urine) was used this 2D-LC system. After a rapid and easy sample preparation method based on protein precipitation, the sample was injected into the 2D-LC. The method was developed and validated in terms of the selectivity, LOD, LOQ, linearity, precision, accuracy, and stability. The sample preparation time for the three MIAs was 15 min. The LOD for these compounds was 10 ng/mL, which was lower than the developed HPLC methods. The results showed that this method had good quantitation performance and allowed the determination of gelsemine, koumine, and humantenmine in biological matrices. The method is rapid, exhibits high selectivity, has good sensitivity, and is low-cost, thus making it well-suited for application in the pharmaceutical and toxicological analysis of Gelsemium. [ABSTRACT FROM AUTHOR]