Search

Type 2 diabetes mellitus (T2DM) is associated with brain damage and cognitive decline. Despite the fact that the thalamus involves aspects of cognition and is typically affected in T2DM, existing knowledge of subregion-level thalamic damage and its associations with cognitive performance in T2DM patients is limited. The thalamus was subdivided into 8 subregions in each hemisphere. Resting-state functional and structural MRI data were collected to calculate resting-state functional connectivity (rsFC) and gray matter volume (GMV) of each thalamic subregion in 62 T2DM patients and 50 healthy controls. Compared with controls, T2DM patients showed increased rsFC of the medial pre-frontal thalamus, posterior parietal thalamus, and occipital thalamus with multiple cortical regions. Moreover, these thalamic functional hyperconnectivity were associated with better cognitive performance and lower glucose variability in T2DM patients. However, there were no group differences in GMV for any thalamic subregions. These findings suggest a possible neural compensation mechanism whereby selective thalamocortical functional hyperconnectivity facilitated by better glycemic control help to preserve cognitive ability in T2DM patients, which may ultimately inform intervention and prevention of T2DM-related cognitive decline in real-world clinical settings.

Understanding how microbial communities adapt to environmental stresses is critical for interpreting ecological patterns and microbial diversity. In the case of the Gobi Desert, little is known on the environmental factors that explain hypolithic colonization under quartz stones. By analyzing nine hypolithic communities across an arid gradient and the effects of the season of the year in the Hexi Corridor of this desert, we found a significant decrease in hypolithic colonization rates (from 47.24 to 15.73%) with the increasing drought gradient and found two distinct communities in Hot and Cold samples, which survived or proliferated after a hot or a cold period. While Cold communities showed a greater species diversity and a predominance of Cyanobacteria, Hot communities showed a predominance of members of the Proteobacteria and the Firmicutes. In comparison, Cold communities also possessed stronger functions in the photosynthesis and carbon metabolism. Based on the findings of this study, we proposed that the hypolithic communities of the Hexi Corridor of the Gobi Desert might follow a seasonal developmental cycle in which temperature play an important role. Thus after a critical thermal threshold is crossed, heterotrophic microorganisms predominate in the hot period, while Cyanobacteria predominate in the cold period.

The outer dimensions and 3D model of ring forgings in industrial production are the important parameters to ensure the quality of the products. In order to realize the measurement of the outer dimensions and 3D model of the ring forgings, a measuring method for the ring forgings combining with a CCD camera and a 2D laser scanner is proposed in this paper. Firstly, the image information of the ring forgings is obtained by the CCD camera. The radiuses of different sections for ring forgings are acquired by pixel calibration and edge detection. Secondly, the point cloud data of different sections are obtained by laser scanner with the movement of the transmission mechanism. Then, the position discrimination method of straight line fitting is used to reduce the error data. And the radius matching method is used in the further processing of the point cloud data based on image detection, and the point cloud data with high accuracy is further extracted. Finally, the 3D point cloud data and 3D model of the ring forgings are obtained by rotating the 2D point cloud data. The outer dimensions of forgings are derived from the 3D model. The experiments were carried out with two different ring forgings. According to the experimental results, the feasibility of the method proposed in this paper is verified.

An accurate understanding of the breakage mechanism of broken coal and rock mass and its coupling relationship with stress and porosity is important for achieving efficient and safe production in coal mines, storage and utilisation of gas and water resources in goafs, and environmental ecological protection. In this study, a novel 3D simulation method is proposed for broken rock and coal granule compaction and breakage. This method can simulate the re-breakage characteristics of broken rock and coal granules during laterally confined compression (LCS). On this basis, numerical simulations combined with laboratory tests are conducted to quantitatively analyse the stress, porosity, and breakage rate evolution characteristics of broken rock granules during LCS. The entire loading process of broken rock granules is divided into three stages: self-adjustment, broken, and elastic. The stress evolution and breakage evolution characteristics of the broken rock granules during each loading stage are delineated. The breakage characteristics of broken rock granules are the main reasons for the evolution of stress, porosity, and breaking rate. In the elastic stage, only uniform compressive stress acts on the broken rock granule, inhibiting further breakage of the sample. When the loading stress reaches the tensile strength of the broken rock granules, the breakage rate of the models increases the fastest. The effects of the broken sample strength and sample size on the breakage characteristics and stress evolution law of the broken models during loading are further discussed. The secant modulus of the broken models in the elastic stages is approximately equal to the elastic modulus of the coal and rock samples. The coordination number evolution law of the broken granules during loading is the main factor affecting its breakage.

Microbiota of lower female reproductive tract is special in its microorganism composition with Lactobacillus as the predominant bacteria. A few of Lactobacillus species have been identified to benefit the inhibition of inflammatory and malignant diseases. Lacticaseibacillus casei LH23 is a strain isolated from traditional fermented food and had been demonstrate to ameliorate DSS-induced colitis in mice. In the present study, effects of Lacticaseibacillus casei LH23 on cervical cancer cells were investigated. Supernatants of lysates and heat-inactivated Lacticaseibacillus casei LH23 were found to inhibit the expression of human papillomavirus genes E6/E7 which is the main causative factor of cervical cancer. With MTT, EdU staining, and TUNEL staining assays, Lacticaseibacillus casei LH23 was shown to suppress the proliferation and induced the apoptosis of cervical cancer cells. Additionally, with wound-healing and Western-blot assays, Lacticaseibacillus casei LH23 was shown to slowdown the migration of cervical cancer cells and altered the expression of metastasis-related genes. These results demonstrated the anti-cervical cancer potential of Lacticaseibacillus casei LH23.

Underground water reservoir (UWR) technology has been used to protect mine water resources. The main underground space for UWRs is the caving zone formed by longwall mining. Broken rock mass movement in the caving zone affects the porosity distribution and seepage characteristics during the UWR’s circulation, storage, and discharge. We used a fluid-solid coupled model, implemented in PFC3D and combined with Python, to simulate water seepage in the caving zone. The influence of particle size and fluid element size on the error of the simulation results was analysed. Then, we investigated the effect of seepage on broken rock mass porosity under different stress states. Simulations with various particle sizes and compaction stresses show that the average displacement of broken rock decreases exponentially with increased stress. Because large broken particles form the primary bearing structure in the model, it is mostly small particles that move under high-stress levels, so porosity is less affected. Larger particles also migrate if the compaction stress is low; this significantly changes the porosity and leads to roof uplift. Finally, we designed an engineering scale model based on our simulation method using the actual UWR situation in a coal mine.

This study investigated the development and formation of ground fissures at panel 12,401 of the Shangwan Colliery in the Shendong mining area, characterized by the current largest mining height and an aeolian sand surface in China. An integrated monitoring method was employed to examine the ground subsidence, distribution and development pattern of ground fissures, and the relationship between fissure width and depth, including an unmanned aerial vehicle, ground penetrating radar, and real-time kinematic and manual measurements. Then, the development and formation mechanisms of ground fissures were elucidated through theoretical analysis and physical simulation. The results indicate that ultra large mining height longwall panel extraction causes a greater ground subsidence and horizontal deformation than those of the conventions, resulting in more severe damage in the permanent margin area. The ratio of burial depth to mining height (H/M) decreases to less than 30 due to the ultra large mining height, and deep-burial panel displays the characteristics of shallow coal seam mining, such as “step subsidence”. The sliding instability of the primary key stratum causes the simultaneous cutting-off of the aeolian sand layer to form step-like ground fissures. The cause of the tensile fissures is the horizontal surface deformation exceeding the deformation threshold of the aeolian sand layer, and the dynamic tensile fissures were self-restored in 2 weeks as the panel advanced. Step-like fissures connected the working face with the ground, but the depth of the tensile fissures was less than 5.0 m and increased linearly with the fissure width.

As coal mining is extended from shallow to deep areas along the western coalfield, it is of great significance to study weakly cemented sandstone at different depths for underground mining engineering. Sandstones from depths of 101.5, 203.2, 317.3, 406.9, 509.9 and 589.8 m at the Buertai Coal Mine were collected. The characteristic strength, acoustic emission (AE), and energy evolution of sandstone during uniaxial compression tests were analyzed. The results show that the intermediate frequency (125–275 kHz) of shallow rock mainly occurs in the postpeak stage, while deep rock occurs in the prepeak stage. The initiation strength and damage strength of the sandstone at different depths range from 0.23 to 0.50 and 0.63 to 0.84 of peak strength (σc), respectively, decrease exponentially and are a power function with depth. The precursor strength ranges from 0.88σc to 0.99σc, increases with depth before reaching a depth of 300 m, and tends to stabilize after 300 m. The ratio of the initiation strength to the damage strength (k) ranges from 0.25 to 0.62 and decreases exponentially with depth. The failure modes of sandstone at different depths are tension-dominated mixed tensile-shear failure. Shear failure mainly occurs at the unstable crack propagation stage. The count of the shear failure bands before the peak strength increases gradually, and increases first and then decreases after the peak strength with burial depth. The cumulative input energy, released elastic energy and dissipated energy increase with depth. The elastic release rate ranges from 0.46 × 10–3 to 198.57 × 10–3 J/(cm3 s) and increases exponentially with depth.

Fast development of combination of nanotechnology with traditional Chinese medicine (TCM) broadens the field of application of TCM. Besides, it increases the research ideas and contributes to TCM modernization. As expected, TCM will be developed into the nanodrug delivery system by nanotechnology with careful design, which will enhance the medicinal value of TCM to cure and prevent disease based on benefits brought by nanometer scale. Here, formulations, relevant preparations methods, and characteristics of nano-TCM were introduced. In addition, the main excellent performances of nano-TCM were clearly elaborated. What is more, the review was intended to address the studies committed to application of nanotechnology in TCM over the years, including development of Chinese medicine active ingredients, complete TCM, and Chinese herbal compounds based on nanotechnology. Finally, this review discussed the safety of nano-TCM and presented future development trends in the way to realize the modernization of TCM. Overall, using the emerging nanotechnology in TCM is promising to promote progress of TCM in international platform. Recent researches on modernization of traditional Chinese medicine (TCM) urged by nanotechnology are introduced, and formulations, advantages, and applications of nano-TCM are reviewed to provide strong proofs.

With annually increased coal mining depth, gas extraction becomes more and more problematic. The gas extraction effect depends on coal seam permeability, which, in turn, is affected by many factors, including loading and unloading stresses and strains in the coal seam. Stresses induce internal cracks, resulting in cleats and gas emission channels, the coal seam permeability permanently changes accordingly. To clarify the stress-induced effects on coal seam permeability, this survey summarized the available approaches used to link the stress path and seepage law in the coal body seepage law, which can be classified into two design methods: single load variation and combined field mining method. The characterization methods used to observe the surface of coal samples and three-dimensional reconstruction include electron microscopy, CT scanning, and Nuclear Magnetic Resonance (NMR). According to the stress paths designed by the above two approaches, the seepage laws and similarities of three kinds of coal samples with the fractured structure were summarized in this paper. The following directions are recommended to study the seepage law of coal bodies with three kinds of fractured structures under stress. Firstly, the stress path of the experimental coal body should be designed by the combined field mining method. The stressed environment of a deep coal seam is complicated, and the axial and confining pressures change simultaneously. Therefore, one cannot fully reflect the real situation on-site by studying permeability evolution alone. Secondly, during the coal seam mining, the stressed state changes from time to time, and the development of coal seam fractures is affected by mining. When studying the stress effect on seepage of coal samples, the fractured structure of coal samples should be considered. Finally, the available structural characterization methods of coal samples can be combined with the 3D printing technology, which would produce artificial samples with the fractured structure characteristics of natural coal.

Characterizing the permeability evolution and methane release is of great significance for the safe mining of the high gas outburst seams, as well as coal and gas simultaneous extraction. It contributes to reduce methane emissions from coal mining for greenhouse effect control. Theoretical analysis, laboratory testing, and numerical simulation are widely used methods to characterize the permeability and methane release with the treatment process of pressure-relief mining. However, these methods cannot fully reflect the complexity of filed practice. In this study, we report the effectiveness of protective coal seam (PCS) mining and the pressure-relief area in the protected coal seam (PDCS) based on detailed and integrated field measurements in a Chinese coal mine. To the best of our knowledge, it is the first time to measure the permeability coefficient and gas pressure evolution in the PDCS during the process of PCS longwall mining. The evolution of the permeability coefficient in the pressure-relief area during PCS mining can be divided into four stages: slowly decreasing, sharply increasing, gradually decreasing, and basically stable. The maximum permeability coefficient is 322 times of the initial value and stabilized at 100 times after the goaf compacted. The gas pressure evolution in the PDCS indicates that the strike pressure relief angle is 52.2° at the active longwall face zone, and 59.3° at the installation roadway side. The inclined pressure relief angles at the lower and upper sides of the longwall face are 75° and 78.9°, respectively. The residual gas content and gas pressure of the PDCS in the pressure-relief area are reduced to less than 6 m3/t and within 0.4 MPa, respectively. The field measurements further prove that pressure-relief mining can prevent coal and gas outbursts in PDCSs. The field observations in this paper can serve as benchmark evidence for theoretical analysis and numerical simulations, and also provide insights into realizing safety mining in similar conditions.

Friction stir welding (FSW) is a relatively new welding technology. Although FSW technology has been widely used in many industries, there is a lack of effective online detection method of process parameters. Weld temperature and tool positioning are two key parameters in the study of process parameters. To realize online measurement of weld temperature and tool positioning in FSW, a measurement method of weld temperature and tool positioning is proposed by designing a new online detection device in FSW. The weld temperature measurement is realized by the material emissivity model based on the principle of infrared temperature measurement. Based on the principle of trigonometric distance measurement, the tool positioning is measured by data processing algorithm. In order to verify the feasibility of the measurement method, the welding processes of aluminum alloy with two thicknesses are detected online. The results show that the weld temperature measurement accuracy of the online detection device is within ± 2%. The measurement of tool positioning is realized. This measurement method proposed in this paper can be applied to the optimization of process design and temperature feedback control.

Friction stir welding (FSW) is a solid-phase welding method. Weld forming and welding quality are related to the heat generated by plastic flow in FSW process. Therefore, it is of great significance to realize the measurement of the viscoplastic heat generated in FSW process. In this paper, based on the working principle of rotary viscometer, the calculation model for the viscoplastic heat in friction stir welding was proposed. The validity of the calculation model was verified by simulation experiment. The correctness of the calculation model was verified by friction stir welding experiment.

High-intensity coal mining activities in China’s western mining area are damaging fragile ecological environments. The key to coordinating ecological protection and coal mining is to understand the law of overlying strata migration in high-intensity mining. However, it is difficult for conventional monitoring methods to efficiently monitor overburden movement in high-intensity mining areas in real time. In this paper, a space-sky-surface (3S) integrated system is proposed to conquer this challenge. This monitoring system consists of three parts: a space monitoring component (a combination of a global navigation satellite system (GNSS) and interferometric synthetic aperture radar (InSAR)), a sky observation component (an unmanned aerial vehicle (UAV) equipped with a measuring camera (MC)), and a surface exploration component (ground-penetrating radar (GPR) and high-density electricity method (HDEM)). This system was successfully applied to the 12,401 longwall face in the Shangwan coal mine (the maximum mining height is 8.8 m). The deformation cloud map of the entire mining area was obtained through InSAR monitoring technology accompanying the 3D laser scanning to improve the accuracy in the local region of 12,401 longwall face. The distribution characteristics and dynamic evolution of surface fractures were obtained using UAV and MC (visible light camera + infrared camera). Using the HDEM and GPR technologies, the fracture development was well detected. Based on the strata movement theory, combined with the monitoring results, a three-dimensional model of overburden rock fracture after 12,401 longwall face mining was constructed. Monitoring results and the fracture model provide a basis for controlling air leakage in the goaf and remediation of surface fracture.

Accurate prediction of the height of the water-conducting fracture zone (WCFZ) is very important for safe coal mining, water resource storage, and protecting the environment. The proportion coefficient of hard rock and the actual height of the top caving coal were defined to predict the height of the WCFZ more accurately. A multivariate regression analysis method was adopted to establish a nonlinear model for predicting the height of the WCFZ based on various factors, including mining height, panel width, proportion of hard rock, mining depth, and extraction rate. Investigations conducted using data from western China show that the ratio of the height of the WCFZ to the mining height obtained using the actual height of the top caving coal is ≈ 20, which is consistent with the distribution of the longwall full-seam mining technology. The values predicted by the multiple regression model in this study are closer to the measured values than those derived using traditional empirical equations, with a relative error

The SNF5-type protein BUSHY plays a role in the regulation of seed germination via the gibberellin pathway dependent on HUB1 in Arabidopsis thaliana. SWITCH/SUCROSE NONFERMENTING (SWI/SNF) complexes play diverse roles in plant development. Some components have roles in embryo development and seed maturation, however, whether the SNF5-type protein BUSHY (BSH), one of the components, plays a role in Arabidopsis seed related traits is presently unclear. In our study, we show that a loss-of-function mutation in BSH causes increased seed germination in Arabidopsis. BSH transcription was induced by the gibberellin (GA) inhibitor paclobutrazol (PAC) in the seed, and BSH regulates the expression of GA pathway genes, such as Gibberellin 3-Oxidase 1 (GA3OX1), Gibberellic Acid-Stimulated Arabidopsis 4 (GASA4), and GASA6 during seed germination. A genetic analysis showed that seed germination was distinctly improved in the bshga3ox1ga3ox2 triple mutant, indicating that BSH acts partially downstream of GA3OX1 and GA3OX2. Moreover, the regulation of seed germination by BSH in response to PAC is dependent on HUB1. These results provide new insights and clues to understand the mechanisms of phytohormones in the regulation of seed germination.

To determine the influence of bedding planes on pure mode I and mixed-mode I–II dynamic fracture toughness (DFT) and crack propagation characteristics of coal, a modified split Hopkinson pressure bar (SHPB) system is used to test notched semi-circular bend (NSCB) specimens. The DFT is calculated by the finite element code Abaqus. Two strain gauges are used to measure the crack propagation velocity and the crack propagation path is recorded by a high-speed digital camera. The results show that bedding planes have significant influences on the effective DFT and crack propagation characteristics of coal. As the bedding-plane angles increase (meaning the geometric positional relationship of the loading direction and the bedding-plane direction transforms from perpendicular to parallel), the effective DFT and peak force decrease. The bedding planes affect the crack initiation direction, and the crack propagation path is jointly determined by the direction of maximum principal stress and the bedding planes. For pure mode I, the crack propagation velocities rise with the increase of bedding-plane angles. However, for mixed-mode I–II, the largest velocity is at the bedding-plane angle of 45°. Moreover, the largest loading velocities at the linear stage of the loading history all occur at 45° and decrease rapidly thereafter.

The goaf is generally consisted of broken coal and rock mass. During the process of overburden strata subsidence and compaction, the broken characteristics directly affect the mechanism and pore characteristics of the caving coal and rock mass. In order to study the influence of particle size on the breakage mechanism of broken coal in the compaction process, the bonded particle model of broken coal sample was carried out to study the breakage characteristics during the compaction with different particle sizes. The stress–strain model of the broken particle model (BPM) during compaction was given. The particle size affects the maximum vertical strain, em, and the stress–strain curve at the beginning of loading. But the particle size has no effect on the slope of the stress–strain curve in linear stage. During the compaction process, the porosity of the BPM can be divided into three stages: slow decrease stage, accelerated decrease stage and slow decrease stage with the increase in strain. Particle size also affects the change in porosity during compaction. The larger the particle size is, the smaller the porosity is at the same strain, but the particle size has no effect on the porosity–stress curve. The breakage rate of BPM increases in S-shape with the increase in strain. When the strain of BPM is over the maximum vertical strain, the particle is basically no longer broken. The larger the particle size is, the larger the residual particle cluster size will be when the breakage rate is stable. The particle sizes' influence on the evolution characteristics of BPM mechanical properties, porosity and breakage rate was demonstrated. The numerical simulation results in this paper can be used for analyzing the compaction characteristics of caving zone at the engineering scale.

The utilization rate of forging materials and the forging process parameters are affected by the shape and size of forgings. The measurement of the shape and size of forgings plays a key role in forging quality and efficiency of industrial production. At present, the laser measurement method is commonly used in forging measurement. The relatively large errors in the laser measurement are mainly caused by the dust at the measurement site, the angular deviation of the object and laser scanner, and the system error of the laser scanner. Therefore, a measurement method of outer diameter of ring forgings based on standard deviation algorithm is presented in this paper. Firstly, after resampling by the standard deviation algorithm, the more accurate data are obtained. Secondly, the good arc feature of the point cloud data is obtained by means of mean filter. Finally, the outer diameter of ring forgings is obtained by using ellipse fitting based on least squares principle. The feasibility of this method is verified by measuring two ring forgings with different outer diameters in the experiment.

The caving zone in goaf can be regarded as a porous medium consisting of broken coal and a rock mass. During the compaction process of broken coal and a rock mass in a caving zone, the re-breakage of the rock and coal affects the compaction stress and pore characteristics of the caving zone. In this study, a discrete element numerical simulation of a broken coal sample based on the bonded particle model (BPM) was carried out to study the evolution characteristics of stress, strain, and breakage during its compaction. The grading equation of the minimum particle size during the simulation process is given based on a laboratory test. This equation can reduce the effect of the sub-particles, which cannot be further broken through the BPM. The stress–strain curve of the BPM during compaction can be divided into two stages using maximum vertical strain, em, and the stress calculation model of these two stages is given. In first stage, there was no effect of the particle strength on em. Here, em of the BPM was equal to the porosity of the BPM minus the initial porosity of the broken particles. The average slope of a straight-line section after em was proportional to the elastic modulus of the coal samples with a ratio of 1.0892. In addition, the particle breakage rate, Bs, and its calculation model were proposed to describe the breakage of the BPM during the compaction process. The evolution characteristics of particle breakage and its correlation with the stress, strain, and particle location are illustrated. The breakage rate of the model increased with increase in strain in an S-shape function. When strain was greater than em, the particles had difficulty breaking again, and the breakage rates of soft coal, medium coal, and hard coal were 96.05%, 87.21%, and 87.78%, respectively. Under the same stress conditions, the breakage rate of soft coal was clearly higher than that of hard coal. The breakage rate increased the fastest when stress was equal to the tensile strength of the coal sample during the compaction process of the BPM.

The dimensions of ring forgings can be analyzed by the point cloud data of ring forgings scanned by laser. The dimensions are the key to evaluating the parameters of ring forgings. Due to the limitation of the scanning angle of the laser scanner, the complete data of the radial section line for the ring forging cannot be obtained through one scan. So the point cloud data of multiple scans are stitched to get the complete data of radial section line. In response to the stitching question, a point cloud data stitching method for ring forgings is proposed in this study. Firstly, the coarse stitching is carried out by using the relationship between the center coordinates of the two data sets. Then, the repeated region is found by the improved Beetle Antennae Search Algorithm (BASA). The repeated region is divided into three parts to find corresponding points in the process of precise stitching. The complete radial section line data can be obtained. Finally, the stitched radial section line is transformed into a complete 3D ring forging model. The comparison experiment results show that the algorithm proposed in this study is simple and fast. The accuracy of this algorithm is verified by extracting the dimensions of the complete model for ring forging.

The stress sensitivity of the persistent fracture and primary joint directly affect the stress and permeability of elastic and shear fracture coal samples in fluid–solid coupling simulation. Therefore, the method to select the parameters of the primary joints and persistent fracture affects the accuracy and reliability of the numerical simulation. This paper introduces the discrete element flow coupling simulation program based on the cubic law. The research on the relationship between flow rates and model parameters, including the mesh number, practice length, aperture, model size, and pressure difference, were performed. The fitting formulas of the flow rates and model parameters were obtained by numerical simulation. Based on the experimental study on the stress permeability of the elastic coal sample and the persistent fracture coal sample, the fluid–solid coupling simulation parameters selection method of the initial joint and persistent fracture is presented. The numerical simulation results with the calculation parameters under triaxial equi-compressive and deviatoric loads are in good agreement with the experimental results, indicating that the method herein can well simulate the relationship between the stress and permeability of the coal samples.

Background Hypoxia has been shown to be able to induce tenogenic differentiation and proliferation of mesenchymal stem cells (MSCs) which lead hypoxia-induced MSCs to be a potential treatment for tendon injury. However, little is known about the mechanism underlying the tenogenic differentiation and proliferation process of hypoxic MSCs, which limited the application of differentiation-inducing therapies in tendon repair. This study was designed to investigate the role of Mohawk homeobox (Mkx) in tenogenic differentiation and proliferation of hypoxic MSCs. Methods qRT-PCR, western blot, and immunofluorescence staining were performed to evaluate the expression of Mkx and other tendon-associated markers in adipose-derived MSCs (AMSCs) and bone marrow-derived MSCs (BMSCs) under hypoxia condition. Small interfering RNA technique was applied to observe the effect of Mkx levels on the expression of tendon-associated markers in normoxic and hypoxic BMSCs. Hypoxic BMSCs infected with Mkx-specific short hair RNA (shRNA) or scramble were implanted into the wound gaps of injured patellar tendons to assess the effect of Mkx levels on tendon repair. In addition, cell counting kit-8 assay, colony formation unit assay, cell cycle analysis, and EdU assay were adopted to determine the proliferation capacity of normoxic or hypoxic BMSCs infected with or without Mkx-specific shRNA. Results Our data showed that the expression of Mkx significantly increased in hypoxic AMSCs and increased much higher in hypoxic BMSCs. Our results also detected that the expression of tenogenic differentiation markers after downregulation of Mkx were significantly decreased not only in normoxic BMSCs, but also in hypoxic BMSCs which paralleled the inferior histological evidences, worse biomechanical properties, and smaller diameters of collagen fibrils in vivo. In addition, our in vitro data demonstrated that the optical density values, the clone numbers, the percentage of cells in S phage, and cell proliferation potential of both normoxic and hypoxic BMSCs were all significantly increased after knockdown of Mkx and were also significantly enhanced in both AMSCs and BMSCs in hypoxia condition under which the expression of Mkx was upregulated. Conclusions These findings strongly suggested that Mkx mediated hypoxia-induced tenogenic differentiation of MSCs but could not completely repress the proliferation of hypoxic MSCs.

Fault-slip induced by underground longwall mining could trigger dynamic failure to nearby mine openings. A better understanding of fault-slip behavior and the associated seismicity is significant for estimating the triggered damage and finding a feasible way to predict potential larger events. In this study, a displacement-dependent moment tensor method is introduced and embedded in the FLAC3D code to simulate both small-scale direct shear test and field-scale mining-induced fault slip. For the direct shear test model, the numerical results agree well with reported experiments in respect to mechanical behavior and seismicity characteristics, such as moment magnitude, frequency-magnitude distribution (FMD), and variation of b-value. Numerical results show that a clustering process is essential to produce realistic FMD, and associated parameters are given. Material heterogeneity of the fault influences the event magnitude. Based on a case study, a field-scale model is built to investigate the fault-slip behavior as a longwall face approaches a fault. For individual contacts, ΔCFF (Coulomb Failure Function) is a useful indicator to evaluate the likelihood of slip. It gradually increases, followed by a quick rise before slip occurs, but sharply drops after slipping. Numerical simulation shows that shear slip initializes on the roof segment of the fault and gradually migrates to the seam and floor segments. Seismicity starts on the roof segment when the longwall face is 100 m away from the fault, but it increases strongly when the distance is less than 50 m and gradually moves toward the seam and floor segments, which is consistent with field observations. Simulated magnitude of the events and the b-value (0.8) also show reasonable agreement with field measurements. The numerical simulation also indicates that a significant drop in b-value usually precedes larger events triggered in the following advancement of the longwall face, which can be regarded as a precursor for larger events.

Gene therapy is considered a potential treatment for Duchenne muscular dystrophy (DMD). Researchers have been working on this for many years to find effective therapeutic targets. Here, we found that MRTF-A (myocardin-related transcription factor A) could activate the transcription of L-type Ca2+-channel-related protein CACNA1S (calcium voltage-gated channel subunit alpha1 S) by binding to the CarG box in the promoter of CACNA1S. However, increased phosphorylation and decreased expression of MRTF-A were observed, along with the expression of CACNA1S reduced in mdx mice. Further, the decreased expression and increased phosphorylation of MRTF-A could inhibit the release of Ca2+ via CACNA1S. Therefore, MRTF-A may be a potential molecular target for the diagnosis and treatment of DMD.

In our previous study, a recombinant duck enteritis virus (DEV) delivering codon-optimized E gene (named as E-ch) of duck Tembusu virus (DTMUV) optimized referring to chicken’s codon bias has been obtained based on the infectious bacterial artificial chromosome (BAC) clone of duck enteritis virus vaccine strain pDEV-EF1, but the expression level of E-ch in recombinant virus rDEV-E-ch-infected cells was very low. To optimize DTMUV E gene expression delivered by the vectored DEV, different forms of E gene (collectively called EG) including origin E gene (E-ori), truncated E451-ori gene, codon-optimized E-dk gene optimized referring to duck’s codon bias, as well as the truncated E451-ch and E451-dk, Etpa-ori and Etpa-451-ori, which contain prefixing chick TPA signal peptide genes, were cloned into transfer vector pEP-BGH-end, and several recombinant plasmids pEP-BGH-EG were constructed. Then the expression cassettes pCMV-EG-polyABGH amplified from pEP-BGH-EG by PCR were inserted into US7/US8 gene intergenic region of pDEV-EF1 by two-step Red/ET recombination, 7 strain recombinant mutated BAC clones pDEV-EG carrying different E genes were constructed. Next, the recombinant viruses rDEV-EG were reconstituted from chicken embryo fibroblasts (CEFs) by calcium phosphate precipitation. Western blot analysis showed that E or E451 protein is expressed in rDEV-E-ori, rDEV-E-ch, rDEV-Etpa-ori, rDEV-E451-ori, rDEV-E451-dk, and rDEV-E451-ch-infected CEFs, and protein expression level in rDEV-E451-dk-infected CEFs is the highest. These studies have laid a foundation for developing bivalent vaccine controlling DEV and DTMUV infection.

The factors affecting permeability change under repeated mining of coal seams are important study aspects that need to be explored. This study combined various stress variation characteristics of protective seam mining and simplified the stress path of repeated mining in protective seam mines. Based on the results from the bespoke gas flow and displacement testing apparatus, seepage tests for simulated repetitive mining were carried out. The results simulated the actual behavior very well. With any drastic increase in the mining influence, the axial deviation stress in the stress path increased, and the greater the difference in coal permeability during the unloading and stress recovery stage, the more substantial the increase in permeability. The change in coal permeability was significantly influenced by the severity of simulated repeated mining cycles. When the mining stress exceeded a critical value, the permeability of the coal sample increased with the increase in the number of loading and unloading cycles, but the reverse was true when the mining stress was lower than the critical value. The effective sensitivity of seepage to the applied stress decreased with an increase in the number of stress cycles. With a decrease in the deviation stress, that is, with lower severity of mining influence, the effective sensitivity of coal seepage to stress gradually decreased.

Bituminous coal in the Xutuan Coal Mine of the Huaibei Mining Bureau (China) is the research object of this study. The influence of moisture content on the porosity of the bituminous coal was investigated from a microscopic perspective by using a high-solution 3D X-ray micro-analyzer. The threshold segmentation method was used to segment the scanning slices of the coal samples. The threshold values of the various media were in the following order (from large to small): minerals, water, matrices, and fractures. The scanning volume and actual volume proportions of the different media in the coal samples with different moisture contents were calculated. The accuracy of the computerized tomography (CT) scanning method in measuring the coal moisture content was verified by comparison with the results obtained using the weighing method. 3D reconstructed coal samples, with different moisture contents, were analyzed, as well as separately reconstructed fractures and water in the coal samples with different moisture contents. The heterogeneity and anisotropy of the coal mass were explained quantitatively by the CT scanning intensity. A commonly used fracture classification method indicated that the primary fracture in the coal sample was a type A fracture. The results of the analysis of water in the coal fracture indicated that the porosity of bituminous coal decreased with the increase in moisture content in conditions of atmospheric pressure and a short immersion period. However, a certain level of porosity remained evident, and the degree of fracture development of the coal samples remained unchanged. This is attributed to the minor volumetric change in the minerals in the coal samples, as the water does not completely occupy the fractures in the coal samples, and the dissolution of the minerals by water is therefore not significant. The reasons for the moisture content affecting gas adsorption, seepage, and strength of a coal body were analyzed from a microscopic perspective. In addition, the types of fractures and water in the coal samples were classified by employing statistics and analyses of volume, surface area, specific surface area, and aspect ratio of the fractures and the water in the coal samples with different moisture contents.

Based on microfocus X-ray computed tomography analyses, the relationship between the characteristics of pore structure and fluid flow behavior was investigated through the single-phase flow experiment. The macroscopic bulk fluid seepage behavior was fundamentally explained by the microscale flow mechanism considering all the porous microstructure analysis of artificial cores. The results indicate that the pore size and connectivity have significant effects on the initial permeability of the rock cores. The permeabilities obtained from different methods have a linear law relationship with porosities in tested artificial cores. The results also suggest that the permeability of core decreases exponentially with the increase in effective stress. The inner different pore structures have an important influence on the stress-dependent fluid flow in synthetic porous rocks. The polynomial equation yields well fittings of the artificial core which has the poor pore sorting characteristic. The permeabilities of the artificial core are more significantly affected by changes in the low effective stress range. The larger the pore channel of the artificial core is, the greater influence on permeability the pressure will have. The stress sensitivity of artificial core increases as the grain diameter decreases. The heterogeneous coefficient and the stress sensitivity of permeability are positively correlated.

Ring forgings are widely used in industrial fields such as trains, construction machinery, bearings, ships, petrochemicals, power generation, aerospace, and nuclear industries. In the dynamic manufacturing process of forgings, the online measurement of radial section line and various dimensional data plays a crucial role in controlling the dimensional accuracy and reducing the reject rate. Therefore, an online measurement method of radial section line for ring forgings based on line laser scanning is proposed. First, a laser scanning measurement system is established for this method. The laser scanning data of the radial uppermost layer section is obtained through this system. Second, all the point cloud data is described as a topological space. The double inverse limit space of the original two-dimensional point cloud information space is established. The topological transitivity between these two spaces is studied. Third, according to the study of the topological transitivity, the relationship of the coordinate position between each point is obtained. Then, a complete radial section line of ring forgings is formed. Finally, the radial dimension data of ring forgings is obtained. Two groups of dimensional measurement experiments have been done. One of the experimental objects is standard ring forging, the other of the experimental objects is non-standard ring forging. The result of the experiment shows that all errors satisfy the requirement of measurement precision.

The reasonable selection of the protective coal mining (PCS) thickness and the quantitative relationship between the mining thickness and the interlayer spacing directly affect the performance of the pressure relief gas drainage and the safe mining of the PCS. Thus, the evolution of the protected coal seam (PDCS) permeability under the different PCS mining thickness in Huainan and Hancheng mining area is simulated by using the stress-damage-seepage coupling model. The results show that the PDCS permeability presents an S type increasing with the increase of the mining thickness. The logistic function formula for quantitative analysis of the relationship between the PCS mining thickness and PDCS permeability is given. The optimal mining thickness of the PCS in Huainan and Hancheng mining area is 1.73 m and 0.96 m, respectively, and the reasonable mining thickness range is 0.87–4.06 and 0.68–1.32 m. Based on the numerical simulation, the quantitative curve between the mining thickness and the interlayer spacing of the upper and lower PCS mining in Hancheng and Huainan mining area is presented. Finally, the reliability of the numerical simulation is verified by the filed measurement of the fracture development in the roof and the permeability of the PDCS.

Streptococcussuis (S.suis) is an important zoonotic pathogen that causes septicaemia, meningitis and streptococcal toxic shock-like syndrome in its host, and recent studies have shown that S.suis could be competent for natural genetic transformation. Transformation is an important mechanism for the horizontal transfer of DNA, but some elements that affect the transformation process need to be further explored. Upon entering the competent state, Streptococcus species stimulate the transcription of competence-related genes that are responsible for exogenous DNA binding, uptake and processing. In this study, we performed conserved promoter motif and qRT-PCR analyses and identified CrfP as a novel murein hydrolase that is widespread in S.suis and stimulated with a peptide pheromone in the competent state through a process controlled by ComX. A bioinformatics analysis revealed that CrfP consists of a CHAP hydrolase domain and two bacterial Src homology 3-binding (SH3b) domains. Further characterization showed that CrfP could be exported to extracellular bacterial cells and lytic S.suis strains of different serotypes, and this finding was verified by TEM and a turbidity assay. To investigate the potential effect of CrfP in vivo, a gene-deletion mutant (ΔcrfP) was constructed. Instead of stopping the natural transformation process, the inactivation of CrfP clearly reduced the effective transformation rate. Overall, these findings provide evidence showing that CrfP is important for S.suis serovar 2 competence.

Antimicrobial peptides have been attracting increasing attention for their multiple beneficial effects. In present study, a novel AMP with a molecular weight of 1875.5 Da, was identified from the genome of Lactobacillus casei HZ1. The peptide, which was named as LHH1 was comprised of 16 amino acid residues, and its α-helix content was 95.34% when dissolved in 30 mM SDS. LHH1 exhibited a broad range of antimicrobial activities against Gram-positive bacteria and fungus. It could effectively inhibit Staphylococcus aureus with a minimum inhibitory concentration of 3.5 μM and showed a low hemolytic activity. The scanning electron microscope, confocal laser scanning microscope and flow cytometry results showed that LHH1 exerted its antibacterial activity by damaging the cell membrane of Staphylococcus aureus. Meanwhile, LHH1 also exhibited anti-cancer cell activities against several cancer cells via breaking the cell membrane of MGC803, HCT116 and C666-1 cancer cells.

Pressure-relief mining is the primary method to remove gas and coal outbursts and realize coal and gas simultaneous extraction in deep, high-gas, and low-permeability coal seams. Numerical modeling has been widely used to evaluate the effectiveness of protective coal seam (PCS) longwall mining, which usually employs experiment-derived permeability models to describe permeability changes and coalbed methane (CBM) flow. Due to the difficulty of tests and data available, published models and parameters were commonly utilized in simulations, which, however, may limit the accuracy of the results because of their case-dependent nature. In this paper, a series of laboratory tests were performed on different damage degree rock mass, i.e., broken rock samples (caving zone), fracture coal samples (fracture zone and swelling deformation zone), and raw coal samples (original zone), to obtain permeability models for different damage zones surrounding the longwall face. Besides the stress states, the experiments also highlight that the damage degree and stress path play vital roles in the permeability changes. The stress sensitivity of permeability in unloading stages is found to be significantly lower than that in loading stages, indicating the importance of the stress path when simulating longwall mining-induced permeability changes. A stress path-dependent permeability law was proposed, and the associated algorithm was designed and embedded into the FLAC3D code. For the first time, the stress path-dependent permeability law was employed to simulate the pressure relief, permeability enhancement, and CBM flow in the protected coal seam (PDCS) when longwall mining is executed in the upper PCS. Field measurements proved the feasibility and accuracy of the new numerical method. Numerical results also suggest the common loading permeability model overestimates the effectiveness of the pressure relief mining. This study highlights the significant role of stress path-dependent permeability laws to accurately predict the permeability changes and CBM flows in pressure relief mining.

BackgroundFoxp3+CD4+regulatory T cells (Treg) constitutes a key event in autoimmune diseases. STAT5b is the critical link between the IL-2/15 and FOXP3, the master regulator of Treg cells.MethodsThe CD3+T cell and Foxp3+CD4+regulatory T cells were overexpressioned or knockdown MKL-1 and STAT5a and tested for Treg cell development and function. Direct interaction of MKL-1 and STAT5a were analyzed by coimmunoprecipitation assays, Luciferase assay, Immunofluoresence Staining and Yeast two-hybrid screening. The effect of MKL-1 and STAT5a on the Treg genes expression was analyzed by qPCR and western blotting and Flow cytometry.ResultsHowever, the molecular mechanisms mediating STAT5b-dependent Treg genes expression and Treg cell phenotype and function in autoimmune diseases are not well defined. Here, we report that the MKL-1 is a coactivator for the major Treg genes transcription factor STAT5b, which is required for human Treg cell phenotype and function. The N terminus of STAT5b, which contains a basic coiled-coil protein–protein interaction domain, binds the C-terminal activation domain of MKL-1 and enhances MKL-1 mediated transcriptional activation of Treg-specific, CArG containing promoters, including the Treg-specific genes Foxp3. Suppression of endogenous STAT5b expression by specific small interfering RNA attenuates MKL-1 transcriptional activation in cultured human cells. The STAT5b–MKL-1 interaction identifies a role of Treg-specific gene regulation and regulated mouse Treg cell development and function and suggests a possible mechanism for the protective effects of autoimmune disease Idiopathic Thrombocytopenic Purpura (ITP).ConclusionsOur studies demonstrate for the first time that MKL-1 is a coactivator for STAT5b, the regulator of Treg cell development and function.

Changes in gas pressure or external stress cause changes in permeability; furthermore, the severity of stress disturbance in these situations can easily produce plastic yielding in the coal seam. Variations in coal seam permeability are also different between the elastic and plastic zones during the process of gas drainage. Therefore, it is necessary to consider gas pressure and external stress during pressure relief gas drainage in order to provide guidance for drilling in terms of location, timing, and pressure. An experimental study explored the relationship between external stress, gas pressure, and permeability in elastic and plastic fracture coal samples. This paper then conducts a numerical simulation of gas drainage according to the model, using the FISH programming language embedded in the FLAC3D numerical simulation software. The experimental results demonstrate that permeability in elastic coal samples first decreased and then increased with increasing gas pressure; in contrast, permeability in fractured coal samples decreased with increasing gas pressure and did not appear to increase at all within the tested gas pressure range. Decreases in permeability accompanied increases in gas pressure under constant effective stress; this indicates that decreases in effective stress lead to increases in permeability when the gas pressure exceeds the critical gas pressure under constant external stress. In contrast, when the gas pressure is less than the critical value, the Klinkenberg effect and matrix adsorption expansion play a major role in permeability changes. The influence of the Klinkenberg effect and adsorption on permeability decreases as gas pressure increases under the same effective stress or external stress conditions. Permeability and its sensitivity to gas pressure decrease with increasing effective stress or external stress. Meanwhile, the simulation demonstrates that permeability in the plastic zone increases in a nonlinear fashion as gas pressure decreases. These permeability increases can be divided into four stages: a rapid increase, gradual smoothing, a second slow increase, and ultimate stability.

To establish stable infliximab-expressing Chinese hamster ovary (CHO) cells with high tolerance to serum-free culture. Bcl-2 antagonist/killer 1 (BAK1), which is a key mediator of the apoptosis pathway, was disrupted, and infliximab, which is a broadly used monoclonal antibody for the treatment of rheumatoid arthritis and other autoimmune diseases, was incorporated into the BAK1 locus of the CHO chromosome using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas genome-editing technique. The activating effects of serum starvation on BAK1 and cytochrome C (CytC) were suppressed in the genome-edited cells, and the ability of the cells to resist the serum starvation-induced loss of mitochondrial membrane potential and apoptosis was increased, as indicated by the results of polymerase chain reaction (PCR), flow cytometry, enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC) analysis. In addition, during subsequent passages, infliximab could be stably produced in the genome-edited CHO cells, and the recombinant antibody could effectively antagonize the cytotoxic effect of tumor necrosis factor α (TNFα). A CHO cell line capable of stably expressing infliximab and adapting to serum-free culture was constructed. This work lays the foundation for the development of infliximab biosimilars.

To achieve biosynthesis of caffeoylmalic acid from glucose in engineered Escherichia coli. We constructed the biosynthetic pathway of caffeoylmalic acid in E. coli by co-expression of heterologous genes RgTAL, HpaBC, At4CL2 and HCT2. To enhance the production of caffeoylmalic acid, we optimized the tyrosine metabolic pathway of E. coli to increase the supply of the substrate caffeic acid. Consequently, an E. coli–E. coli co-culture system was used for the efficient production of caffeoylmalic acid. The final titer of caffeoylmalic acid reached 570.1 mg/L. Microbial production of caffeoylmalic acid using glucose has application potential. In addition, microbial co-culture is an efficient tool for producing caffeic acid esters.