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The innovative technology of microbially induced calcium carbonate precipitation (MICP) soil modification is widely used in soil reinforcement, soil remediation, environmental remediation and other fields, and has gradually become a hot research direction. Recent research is more focused on the overall physical and mechanical characteristics of the uniform reinforced specimen. There is limited research on the distribution characteristics of calcium carbonate along the seepage path during the reinforcement process. However, the distribution characteristics of calcium carbonate play a significant role in the physical and mechanical characteristics of the solid, especially in the large-scale MICP reinforcement process. In this study, based on the microbial mineralization reaction tests of different concentrations of cement solution at the laboratory sample scale, the calcium carbonate distribution on the surface of the sample at the microscale SEM observation and the CT scanning reconstruction of the micro pore structure characteristics of the microbial reinforced soil, we discussed the characteristics of the non-uniform reduction of calcium carbonate distribution and porosity in the process of microbial consolidation. Based on the Kozeny-Carman equation, the conceptual model of effective porosity was introduced, and the time relationship between porosity and calcium carbonate precipitation was considered to establish a bio-chemical-seepage multi-physics field coupling model. The precipitation of calcium carbonate in the axial direction of the model sample exhibits an uneven feature of more at the top and less at the bottom, and the distribution characteristics of porosity also show an uneven feature of more at the top and less at the bottom.

Abstract River ethics encompasses the values, moral principles, and behavioral norms that govern and regulate the relationship between humans and rivers. Constructing rivers ethics breaks through the traditional ethical dimension that is limited to interpersonal judgment and extends the moral relationship from solely between humans to between humans and river life. China's eco‐civilization drive elucidates that harmony between humans and rivers are the core concept of constructing river ethics. This paper discusses the values, foundation, moral principles, and behavioral norms of river ethics, and forms the theoretical framework of river ethics.

Previous studies on the susceptibility assessment of regional landslides mainly focused on comparing and improving the results of different evaluation models, while neglected the preservation of information on selected disaster-causing factors and the issue of how to unify factor dimensions. To explore the correlation and dimensionality of disaster causing-factors and their impact on susceptibility assessment, this study selected 12 factors such as elevation, slope, aspect, and terrain undulation, and used new factors extracted from principal component analysis in susceptibility assessment in the northern Jingyuan County. Data standardization, landslide density, and information quantity substitution methods were used to unify the dimensionality of disaster-causing factors. The landslide susceptibility zoning map was drawn based on the GIS platform in the study area. The accuracy of the susceptibility assessment of each mode was evaluated by the receiver operating characteristic curve. The results show that among the information model, the logistic regression model, and the perceptron model, the accuracy of the model evaluation obtained by the factors processed by principal component analysis is the highest. Using the information value substitution method to unify the dimensions of factors can further improve the accuracy of the evaluation of the logistic regression model and the perceptron model. The perceptron model has the highest accuracy (AUC=0.936 7), which is superior to the information model (AUC=0.917 3) and the logistic regression model (AUC=0.927 2). This is an ideal model for the landslide susceptibility assessment in the study area and should be given priority. The results can provide the basic theoretical information for disaster prevention and mitigation in similar areas.

The rockburst risk prediction based on microseismic (MS) data is an important research task in deep mine safety prevention. However, the lack of systematic research on explicit prediction indexes and the waste of a large amount of unlabeled data are still two main problems that hinder the development of rockburst prediction. In this paper, the acoustic emission (AE) event distribution at each coal rock deformation and failure stage is studied based on the laboratory experiment. The spatial-temporal evolution of rockburst in MS data of coal mine fields is explored. Based on systematic research of the AE and MS distribution features considering the physical logic of coal rock mass failure, nine different rockburst prediction indexes are employed to describe the MS data features before rockburst. Then, according to the rockburst prediction indexes, a new self-supervision rockburst risk prediction algorithm is constructed, consisting of the pre-trained model and fine-tuning model with the same encoder and decoder structure. The pre-trained model is trained with unlabeled MS data to automatically learn rockburst prediction index features by reconstructing the masked indexes. Based on the pre-trained encoder and decoder parameters, the fine-tuning model is trained with the labeled MS data to predict rockburst risk. A large number of experiments show that the proposed rockburst prediction self-supervision algorithm is far superior to previous algorithms, by effectively utilizing unlabeled data. The ablation experiment also proves the validity of the studied rockburst prediction indexes.

As a new engine driving economic development, new digital infrastructure plays a significant role in enhancing green total factor productivity. Based on 2011–2020 panel data covering 30 Chinese provinces, this study empirically investigates the effects and mechanisms of new digital infrastructure on green total factor productivity. The results show that new digital infrastructure can significantly improve regional green total factor productivity, and this conclusion remains valid after a series of robustness tests and regressions of instrumental variables. Further mechanism research shows that new digital infrastructure indirectly promotes the growth of green total factor productivity by improving capital misallocation and driving technological innovation, while there is no mediating mechanism of labor misallocation. In addition, there is significant heterogeneity in the impact of new digital infrastructure on green total factor productivity. Especially during periods of high government attention, in the eastern regions, and in areas with higher levels of human capital, the positive incentive effect of new digital infrastructure is more significant. This study provides empirical evidence and policy references for promoting and amplifying the green growth effects of new digital infrastructure.

Objective To investigate the allele frequencies polymorphic distribution of Duffy, Kidd and Diego blood group systems in Dongxiang ethnic group in Gansu Province. Methods Blood samples of 100 unrelated blood donors were randomly selected from Dongxiang ethnic group in Gansu from January to December 2017. Allelic typing of Duffy, Kidd and Diego blood groups was performed by fluorescence PCR. Results The allele frequencies of Duffy, Kidd, and Diego blood group systems of Dongxiang ethnic group were 0.835 for Fy*01, 0.165 for Fy*02, 0.570 for Jk*01, 0.430 for Jk*02, 0.020 for DI*01, 0.980 for DI*02, respectively. No Fy(a-b-), Jk(a-b-), Di(a+b-) rare phenotypes were found. The antigen incompatibility rates of Fya/Fyb, Jka/Jkb, Dia/Dib of Duffy, Kidd, and Diego blood group systems were 23.76%, 37.01% and 3.84%, respectively. Conclusion The allele frequencies distribution of Duffy, Kidd and Diego blood group systems in Dongxiang ethnic group in Gansu were polymorphic and has unique ethnic distribution characteristics.

On September 18, 2020, a landslide occurred on the left bank of Tianbao Reservoir in Tianbao Village, Sihe Town, Jingning County, Pingliang City, Gansu Province. The landslide is 180 m long, 240 m wide, 48.5×104 m3 in volume, and 191° in main sliding direction, which is the revival of the old loess-mudstone landslide. Landslide destroys the excavated slope and highway subgrade, which seriously threatens the normal construction of Tianbao Reservoir. Through field investigation, geotechnical test and calculation, the geological conditions, basic characteristics and causes of landslide formation in Tianbao Reservoir were discussed, and the stability of landslide was analyzed by simplified Janbu method. The study found that the formation conditions of the landslide are mainly three aspects : the geological foundation of the old landslide, the excavation of the front edge of the slope, and the continuous heavy rainfall. That is, the old landslide is caused by the large-scale excavation of the slope toe and the heavy rainfall. The stability calculation results show that after excavating the slope toe, the stability coefficient is less than 0.98 under the rainstorm condition, which is in the unstable sliding state. After sliding, the stability coefficient of each working condition is less than 1.05, which is in the unstable-unstable state.

Microbially induced carbonate precipitation (MICP) technology is employed to reinforce the surface soil of a dam, aiming to prevent erosion caused by water flow and damage to the dam slope. The relationship between penetration depth, calcium carbonate content, and bonding depth was investigated at eight measuring points on the sand slope surface of a mold under different reinforcement durations. It was observed that as grouting reinforcement times increased, there was a gradual increase in calcium carbonate content but a rapid rise in penetration resistance. Moreover, the bonding depth of sand on the bio-reinforced sand slope increased with higher levels of calcium carbonate content. Microbial grouting reinforcement enhanced soil particle bonding force, requiring water flow to overcome this force for activation of sand particles. Consequently, microbial grouting reinforcement significantly improved shear strength and critical starting flow velocity on sand slope surfaces. The experimental results demonstrated that after MICP surface treatment through spraying, a dense and water-stable hard shell layer composed of bonded calcium carbonate and soil particles formed continuously on sample surfaces, effectively enhancing the strength and erosion resistance of sandy soils. These findings provide reliable evidence for silt slope reinforcement and dam erosion prevention.

Abstract With the efficient cross-linking abilities and the flexible regulation abilities to the performances of cross-linked products, the multi-functional aliphatic epoxides were once widely used to cross-link the collagen-based materials in the last century. In present work, the multi-functional epoxides were used to construct and cross-link collagen sponges for tissue engineering scaffolds, which was hoped to board the theoretical system of epoxides and explore their potentials for modern applications. The bi- to tetra-functional epoxides were used to cross-link collagen solutions and establish the gel-like precursors, then using freeze-drying to form the final sponges. The SEM observed that the sponges had shown regular porous structures with a wide range of pore sizes from 160 to 440 μm. The sponges had presented the resistance to enzymatic degradation, shape-remaining ability, and reversible compressibility in aqueous environments, which all could be regulated through the functionalities of epoxides. The regulation abilities of multi-functional epoxides on the performances of sponges had been mainly achieved through the cross-linking degrees that the higher functionality of epoxides would bring higher cross-linking degree. Such higher cross-linking degrees could enhance the elastic behaviors of gel-like precursors, and improve the compressive strengths and thermal stabilities of sponges. Nevertheless, the multi-functional epoxides had barely affected the safety of collagen sponges at the cellular level according to the results of CCK8 assay and the SEM and CLSM images of L929 fibroblasts cultured on the cross-sections of sponges. Graphical abstract

Transglutaminase (EC 2.3.2.13, TGase), an enzyme that catalyzes the formation of covalent cross-links between protein or peptide molecules, plays a critical role in commercial food processing, medicine, and textiles. TGase from Streptomyces is the sole commercial enzyme preparation for cross-linking proteins. In this study, we revealed that the SOS response repressor protein LexA in Streptomyces mobaraensis not only triggers morphological development but also enhances TGase synthesis. The absence of lexA significantly diminished TGase production and sporulation. Although LexA does not bind directly to the promoter region of the TGase gene, it indirectly stimulates transcription of the tga gene, which encodes TGase. Furthermore, LexA directly enhances the expression of genes associated with protein synthesis and transcription factors, thus favorably influencing TGase synthesis at both the transcriptional and posttranscriptional levels. Moreover, LexA activates four crucial genes involved in morphological differentiation, promoting spore maturation. Overall, our findings suggest that LexA plays a dual role as a master regulator of the SOS response and a significant contributor to TGase regulation and certain aspects of secondary metabolism, offering insights into the cellular functions of LexA and facilitating the strategic engineering of TGase overproducers.

Transglutaminases (TGases) have been widely used in food, pharmaceutical, biotechnology, and other industries because of their ability to catalyze deamidation, acyl transfer, and crosslinking reactions between Ƴ-carboxamide groups of peptides or protein-bound glutamine and the Ɛ-amino group of lysine. In this study, we demonstrated an efficient systematic engineering strategy to enhance the synthesis of TGase in a recombinant Streptomyces mobaraensis smL2020 strain in a 1000-L fermentor. Briefly, the enzymatic properties of the TGase TGL2020 from S. mobaraensis smL2020 and TGase TGLD from S. mobaraensis smLD were compared to obtain the TGase TGLD with perfected characteristics for heterologous expression in a recombinant S. mobaraensis smL2020ΔTG without the gene tgL 2020. Through multiple engineering strategies, including promoter engineering, optimizing the signal peptides and recombination sites, and increasing copies of the expression cassettes, the final TGLD activity in the recombinant S. mobaraensis smL2020ΔTG: (PL2020-spL2020-protgLD-tgLD)2 (tgL2020 and BT1) reached 56.43 U/mL and 63.18 U/mL in shake flask and 1000-L fermentor, respectively, which was the highest reported to date. With the improvement of expression level, the application scope of TGLD in the food industry will continue to expand. Moreover, the genetic stability of the recombinant strain maintained at more than 20 generations. These findings proved the feasibility of multiple systematic engineering strategies in synthetic biology and provided an emerging solution to improve biosynthesis of industrial enzymes.

ABSTRACTPeople often simultaneously expose to acceptable/tolerable daily intake of food additives and pesticides in daily life. Exposure in adult rodents to acceptable/tolerable daily intake of food additives and pesticides chemical mixtures (AFACM) is reported to cause health damage. Our recently study reported that AFACM exposure of pregnant mice resulted in neuroinflammation and abnormal emotional behaviours in offspring. Here, we found that neutralising IFN-γ with neutralising antibodies completely blocked the influences induced by maternal AFACM exposure, including the increased IFN-γ level in serum, increased IFN-γ, interleukin-6 and tumour necrosis factor-α levels in prefrontal cortex(PFC) in offspring on postnatal day(PND)7, the abnormal emotional behaviours in offspring on PND56, and the decreased of ATPase phospholipid flippase 8A2(ATP8A2) in the PFC of offspring on PND7. In sum, maternal AFACM exposure induced the PFC neuroinflammation, abnormal emotional behaviours and decreased PFC ATP8A2 expression through increasing systemic IFN-γ in offspring.

Objective: To investigate whether Acori Graminei Rhizoma (AGR) volatile oil can reduce inflammatory pain-induced pain-related mood in rats by downregulating NMDARs-ERK 1/2-CREB signaling pathway. Methods: Thirty-six male SD rats were randomly divided into six groups: control group, sham group, complete Freund's adjuvant (CFA) group, CFA + 0.1 mL/10 g volatile oil group, CFA + 0.2 mL/10 g volatile oil group, and CFA + 0.4 mL/10 g volatile oil group. Six rats in each group were gavaged for 21 days and tested for mechanical pain hypersensitivity and positional avoidance (PEAP) before and after drug treatment. In addition, another batch of thirty-six male SD rats were randomly divided into six groups, including control, sham, CFA, CFA + saline, CFA + 0.1 mg/kg NMDA, and CFA + 0.1 mg/kg Ifenprodil groups. The control group did not receive any treatment, and the sham group received the same volume of sterile saline at the same site. Animals in each group were tested for mechanical pain hypersensitivity and positional avoidance before and after drug treatment. The expression levels of NMDAR1, NMDAR2A, NMDAR2A2B, mGlur1, ERK 1/2, CREB, and c-Fos in the basolateral amygdala (BLA) were determined by immunofluorescent staining and Western blot methods. Results: AGR essential oil could reduce mechanical hyperalgesia and position avoidance in animals caused by CFA, and down-regulate NMDARs, mGlur1/5, ERK 1/2 and CREB expression. While up-regulation of c-Fos expression by NMDAR inhibitor Ifenprodil, reversed the above phenomena. Conclusion: AGR essential oil alleviates inflammatory pain-induced pain-related mood in rats through downregulation of the NMDARs-ERK1/2-CREB signaling pathway.

The development of novel wound dressings, such as aerogels, with rapid hemostasis and bactericidal capacities for pre-hospital care is necessary. To prevent the occurrence of bacterial resistance, antibacterial photodynamic therapy (aPDT) with broad-spectrum antibacterial ability and negligible bacterial resistance has been intensively studied. However, photosensitizers often suffer from poor water solubility, short singlet oxygen (1O2) half-life and restricted 1O2 diffusion distance. Herein, sodium alginate was covalently modified by photosensitizers and phenylboronic acid, and cross-linked by Ca(II) ions to generate SA@TPAPP@PBA aerogel after lyophilization as an antibacterial photodynamic wound dressing. Afterwards, its photodynamic and bacterial capture activities were intensively evaluated. Furthermore, its hemostasis and bactericidal efficiency against Staphylococcus aureus were assessed via in vitro and in vivo assays. First, chemical immobilization of photosensitizers led to an enhancement of its solubility. Moreover, it showed an excellent hemostasis capacity. Due to the formation of reversible covalent bonds between phenylboronic acid and diol groups on bacterial cell surface, the aerogel could capture S. aureus tightly and dramatically enhance aPDT. To sum up, the prepared aerogel illustrated excellent hemostasis capacity and antibacterial ability against S. aureus. Therefore, they have great potential to be utilized as wound dressing in clinical trials.

Wetting deformation has a significant impact on dam safety, and is one of the leading causes of the long-term deformation of dams. For dams to operate safely, it is crucial to precisely estimate the extent of wetting deformation using a reasonable calculation model. This study describes the wetting deformation behavior of gravelly soil core material observed at a hydropower station using a large-scale triaxial wetting test, and the process, characteristics, and mechanism of the wetting deformation are analyzed. The results show that the direction of the wetting deformation exhibits different behaviors influenced by the stress levels. Compared with the significant changes in the wetting direction observed under low stress levels, the changes in the wetting direction under high stress levels appears to lag behind those in wetting deformation. The source of wetting deformation is thought to be the weakening of a material when it encounters water. Thus, a new calculation model of the wetting deformation of gravelly soil core material is proposed. In this model, the wetting strain ratio is in an exponential relationship with the stress levels, and the new model is used to simulate the triaxial wetting test on the gravelly soil core material; its validity and practicability are further evaluated, providing a new computational approach for analyzing the wetting deformation behavior of dams.

The impact risk evaluation for the strip filling of working faces has always been a research hotspot and a difficulty in the field of rock bursts. In this paper, the concept of the critical filling rate is first proposed, and the criterion for identifying the impact risk of the strip filling of a working face is established. Then, the membership function of coal body stress and the coal seam elastic energy index to impact risk was established, and the classification index of the impact risk grade was formed. On this basis, the overall and local evaluation method of the rock burst hazard for the strip filling of working faces was proposed. Finally, the C8301 working face of the Yunhe coal mine was taken as the engineering background, and the impact risk evaluation was carried out. It was found that the overall risk of the C8301 working face was determined as a strong impact risk, and there were six local risk areas, which included two weak impact risk areas, two medium impact risk areas, and two strong impact risk areas. This study can provide guidance and a reference for the impact risk evaluation of strip-filling mining under the same or similar conditions.

Rockfill materials used for dam construction show obvious stress path dependency during construction process. The constitutive model for rockfill materials are mainly established based on conventional triaxial test. This brings some deviation to the numerical calculation for earth rockfill dam engineering, and it is necessary to develop a constitutive model considering stress paths effect. In the framework of generalized plasticity, plastic modulus can be expressed as the function of dilatancy equation and tangent modulus, hence the influence of stress paths on model can be transfer to the dilatancy equation and tangent modulus. This leads to a new method to describe stress-strain response of rockfill under various loading stress paths. Based on the analysis of large-scale triaxial experiments of rockfill materials with various stress paths, we proposed new dilatancy equation and tangent modulus to better describe stress paths effect and corresponding modified generalized plasticity model is established. Through the prediction and comparison of three groups of rockfill materials triaxial tests, the model established in this paper can simulate behaviors of rockfill materials under various stress paths, using only a set of parameters.

Abstract Collagen, as a thermal-sensitive protein, is the most abundant structural protein in animals. Native collagen has been widely applied in various fields due to its specific physicochemical and biological properties. The beneficial properties would disappear with the collapse of the unique triple helical structure during heating. Understanding thermal stability of collagen is of great significance for practical applications. Previous studies have shown the thermal stability would be affected by the different sources, extraction methods, solvent systems in vitro and modified methods. Accordingly, the factors affecting thermal stability of collagen are discussed in detail in this review. Graphical abstract

The Lianghekou earth core rockfill dam to be built in China will be the third highest rockfill dam in the world. This study presents the results of a series of direct shear tests between high plastic clay and concrete to study the shear behavior of contact clay-concrete cushion interface of Lianghekou dam. Results showed that water content and normal stress are significant factors affecting the shear behavior of the interface. The higher shear strength is related to lower water content and higher normal stress, and the shear strength can be formulated by the bifold-line type Mohr–Coulomb strength criterion. It is also found that the interface exhibits mainly two kinds of shear failure modes, that is, sliding failure along the concrete surface and shear failure in the clay matrix nearby the interface. Moreover, a nonlinear elastic model is proposed to simulate the shear behavior of the interface, of which parameters can be quickly estimated by water content. The simulation of the model is compared with the experimental results, and the results show that the model is reasonable and practical.

Abstract The dissolution of collagen in ionic liquids (ILs) was highly dependent on the polarity of ILs, which was influenced by their sorts and concentrations. Herein, the solubility and dispersion degree of collagen in two sorts of ILs, namely 1-ethyl-methylimidazolium tetrafluoroborate ([EMIM][BF4]) with low polarity and 1-ethyl-3-methylimidazolium acetate ([EMIM][Ac]) with high polarity in a concentration range from 10% to 70% at 10 °C were investigated. When 150 mg of collagen was added to 30 mg of ILs, the minimum soluble collagen concentration was 0.02 mg/mL in 70% [EMIM][BF4] with lowest polarity and the maximum was 3.57 mg/mL in 70% [EMIM][Ac] with highest polarity, which indicates that soluble collagen and insoluble collagen fibers were both present. For insoluble collagens, differential scanning calorimetry showed that the thermal-stability was weakened when increasing the ILs concentration and polarity, and the fiber arrangement was looser with a more uniform lyophilized structure, observed by atomic force microscopy and scanning electron microscopy. For soluble collagens, electrophoresis patterns and Fourier transform infrared spectroscopy showed that no polypeptide chain degradation occurred during dissolution, but the thermal denaturation temperature decreased by 0.26 °C~ 7.63 °C with the increase of ILs concentrations, measured by ultra-sensitive differential scanning calorimetry. Moreover, the aggregation of collagen molecules was reduced when ILs polarity was increased as determined by fluorescence measurements and dynamic light scattering, which resulted in an increased loose fiber arrangement observed by atomic force microscopy. If the structural integrity of collagen needs to be retained, then the ILs sorts and concentrations should be considered. Graphical abstract

Aero-engine blades are manufactured by electroforming process with electrodes. The blade electrode is usually machined with five-axis micromilling to get required profile roughness. Tool path planning parameters, such as cutting step and tool tilt angle, have a significant effect on the profile roughness of the micro-fillet of blade electrode. In this paper, the scallop height model of blade electrode micro-fillet processed by ball-end milling cutter was proposed. Effects of cutting step and tool tilt angle the machined micro-fillet profile roughness were predicted with the proposed scallop height model. The cutting step and tool tilt angle were then optimised to ensure the contour precision of the micro-fillet shape requirement. Finally, the tool path planning was generated and the machining strategy was validated through milling experiments. It was also found that the profile roughness was deteriorated due to size effect when the cutting step decreased to a certain value.

Abstract: Characteristics, distribution, temporal and spatial configuration, and effectiveness of hydrocarbon migration pathways have been investigated through geochemical and formation pressure analysis etc, to further reveal hydrocarbon accumulation patterns in the Neogene of the Laixi structural belt, southern Bohai Sea of China. Firstly, three factors, faults, carrier rocks (beds) and mud caprocks of the transporting framework in the Neogene were examined to find out its feature and space configuration and made static state evaluation. It is found that besides the Guantao Formation – lower Minghuazhen Formation No. V oil layers, the No. I – III oil layers in the lower Minghuazhen Formation are also the dominant oil and gas carrier beds. Cutted by the adjustment faults and sealed by mudstone capcocks, the two carrier layers are combined into a “layered cake” type hydrocarbon migration framework. Then the hydrocarbon passage pathways were tracked dynamically and described using nitrogen compounds concentration, formation pressure, fluorescence logging and sand bodies description, which shows that the “T03-T02-T01 mudstone cap layers” separate the Neogene hydrocarbon migration pathways into upper and lower units. The massive sandy conglomerate reservoirs in the Guantao Formation – lower Minghuazhen Formation No. V oil layers are the carrier bed of the lower hydrocarbon migration pathway, while the north-south trending overlapped and connected channel sandbodies in lower Minghuazhen Formation No. I – III oil layers are the carrier bed of the upper unit. Hydrocarbon migrated laterally along the two passage ways, accompanying with differential accumulation. Key words: southern Bohai Sea, Laixi structural belt, hydrocarbon passage framework, dominant migration pathway, hydrocarbon migration pattern, accumulation pattern

Recent neuroimaging studies have shown local brain aberrations in functional dyspepsia (FD) patients, yet little attention has been paid to the whole-brain resting-state functional network abnormalities. The purpose of this study was to investigate whether FD disrupts the patterns of whole-brain networks and the abnormal functional connectivity could reflect the severity of the disease. The dysfunctional interactions between brain regions at rest were investigated in FD patients as compared with 40 age- and gender- matched healthy controls. Multivariate pattern analysis was used to evaluate the discriminative power of our results for classifying patients from controls. In our findings, the abnormal brain functional connections were mainly situated within or across the limbic/paralimbic system, the prefrontal cortex, the tempo-parietal areas and the visual cortex. About 96% of the subjects among the original dataset were correctly classified by a leave one-out cross-validation approach, and 88% accuracy was also validated in a replication dataset. The classification features were significantly associated with the patients' dyspepsia symptoms, the self-rating depression scale and self-rating anxiety scale, but it was not correlated with duration of FD patients (p>0.05). Our results may indicate the effectiveness of the altered brain functional connections reflecting the disease pathophysiology underling FD. These dysfunctional connections may be the epiphenomena or causative agents of FD, which may be affected by clinical severity and its related emotional dimension of the disease rather than the clinical course.

Despite the subjective nature of pain experience with cognitive and affective dimensions, preclinical pain research has largely focused on its sensory dimension. Here, we examined the relationship between learning/memory and nociceptive behavior in rats with combined learning impairment and persistent nociception. Learning impairment was induced by bilateral hippocampal injection of a mixed Aβ solution, whereas persistent nociception produced in these rats by complete Freund's adjuvant-induced ankle inflammation. Those rats with learning impairment showed a diminished development of thermal hyperalgesia and mechanical allodynia and a shorter time course of nociceptive behavior without alteration of their baseline nociceptive threshold. In rats with pre-established hyperalgesia and allodynia due to ankle inflammation, bilateral intra-hippocampal injection of cycloheximide (a protein synthesis inhibitor) promoted the earlier recovery of nociceptive behavior. Moreover, expression of Aβ, NR1 subunit of the N-methyl-D-aspartate receptor, and protein kinase Cγ was upregulated, whereas the choline acetyl transferase expression was downregulated, in the hippocampus, thalamus, amygdala, and/or spinal cord of rats with combined learning impairment and persistent nociception. The data indicate that learning impairment could disrupt the response to a state of persistent nociception, suggesting an important role for cognitive maladaptation in the mechanisms of chronic pain. These results also suggest that a preclinical model of combined learning impairment and persistent nociception may be useful to explore the brain mechanisms underlying the transition from acute to chronic pain.

BACKGROUND: Little is known about the changes of brain structural and functional connectivity networks underlying the pathophysiology in migraine. We aimed to investigate how the cortical network reorganization is altered by frequent cortical overstimulation associated with migraine. METHODOLOGY/PRINCIPAL FINDINGS: Gray matter volumes and resting-state functional magnetic resonance imaging signal correlations were employed to construct structural and functional networks between brain regions in 43 female patients with migraine (PM) and 43 gender-matched healthy controls (HC) by using graph theory-based approaches. Compared with the HC group, the patients showed abnormal global topology in both structural and functional networks, characterized by higher mean clustering coefficients without significant change in the shortest absolute path length, which indicated that the PM lost optimal topological organization in their cortical networks. Brain hubs related to pain-processing revealed abnormal nodal centrality in both structural and functional networks, including the precentral gyrus, orbital part of the inferior frontal gyrus, parahippocampal gyrus, anterior cingulate gyrus, thalamus, temporal pole of the middle temporal gyrus and the inferior parietal gyrus. Negative correlations were found between migraine duration and regions with abnormal centrality. Furthermore, the dysfunctional connections in patients' cortical networks formed into a connected component and three dysregulated modules were identified involving pain-related information processing and motion-processing visual networks. CONCLUSIONS: Our results may reflect brain alteration dynamics resulting from migraine and suggest that long-term and high-frequency headache attacks may cause both structural and functional connectivity network reorganization. The disrupted information exchange between brain areas in migraine may be reshaped into a hierarchical modular structure progressively.