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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.

The electric vehicles (EVs) have played an important role in people's traveling due to the clean energy and friendly environment. Considering the endurance issue of EVs, wireless charging is regarded as a convenient and effective solution. However, the charging power and the efficiency would be greatly affected when the transmitting coil (TC) and the receiving coils are nonaligned. In this article, we present a flexible and high-accuracy positioning device based on electromagnetic balance, which could automatically achieve wireless charging and two-level positioning without communication between TC and EVs during the location. Besides, a six-coil cross-coupled circuit model has been built to optimize the key parameters that affect the positioning accuracy. The theoretical analysis and experimental results show that the proposed structures and location method have certain advantages in positioning accuracy, operation complexity, and practicability. Within the range of first-level positioning, the accuracy could achieve 1 cm. There is a high fitting performance between the simulation and experimental results, which verify the correctness of the theoretical analysis and the validity of the structures. Moreover, an additional comparative experiment has been designed to verify the correctness of the proposed method used in the wireless charging positioning system with ferrite cores and a magnetic shielding layer.

CAR T cell therapy has shown dramatic clinical success in relapsed or refractory (r/r) B-ALL and other haematological malignancies. However, the loss of specific antigens, cell fratricide, T cell aplasia, and normal T cell separation are challenges in treating T cell leukemia/lymphoma with CAR T therapy. CD99 is a promising antigen to target T-ALL and AML as it is expressed on the majority of T-ALL and AML. Here, we isolated a low-affinity CD99 (12E7) antibody, which specifically recognizes leukemia cells over normal bone marrow cells. T cells transduced with an anti-CD99-specific CAR that contained the 12E7 scFv expanded with minor fratricide, maintained their cytotoxic function and mediated powerful antitumour effects. Subsequently, we conducted a pilot clinical study to evaluate the safety and feasibility of therapy with anti-CD99 CAR T cells in 4 patients with r/r T-LBL (n=1), AML (n=2) or myeloid sarcoma (MS) (n=1). The clinical overall response rate (ORR) was 50% (2/4 patients), and 1 patients (25%) achieved complete remission (CR) for 2 month. Mild cytokine release syndrome (CRS) occurred in 2 patients and the CRS no more than grade 2. Together, our results demonstrate that anti-CD99 CAR T cells specifically recognize and efficiently eliminate CD99+ leukemia cells.

The identification and treatment of mining-induced ground fissures are of great significance to mine safety and ecological and environmental protection. In this study, a novel method for ground fissure identification and exploration by infrared remote sensing onboard an unmanned aerial vehicle (UAV) was proposed. Using this method, a region of interest (ROI) that includes ground fissures directly above the middle of a long wall face, No. 12401 in the Shangwan coal mine, was monitored continuously during the day and night. Direct field measurements of ground fissure properties were also conducted to provide a calibration dataset for UAV measurements. Using the direct visible image at 5:00 pm as a reference, the average errors of the length and maximum width of Fissure I obtained from infrared images from 9:00 pm to 5:00 am on the next day, were estimated to be 1.8% and 6.5%, respectively. The diurnal variation of the fissure temperature is sinusoidal, and the range of temperature variation in the fissure decreases with the increase in depth. There is an apparent difference between the two common types of fissures depending on whether the fissure has a direct connection to an aquifer or a goaf. In this study, UAV, infrared thermal imager, and visible light camera data were successfully employed to effectively identify mining-induced ground fissures. In addition, the fissure detection error was validated, and the appropriate time for utilizing this method was obtained. Our results show that to identify the two aforementioned types of fissures, monitoring should be conducted between 3:00 am and 5:00 am. This study lays a foundation for the study and application of UAV and infrared thermal imagers for the identification of ground fissures induced by underground mining in large areas.

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.

BACKGROUND: Illness duration is the main index of cumulative illness severity during depression progression. Corpus callosum (CC) damage is among the most replicated neurobiological findings in major depressive disorder (MDD). We aimed to investigate the nature and extent of the association between illness duration and CC changes. METHODS: Ninety-six MDD patients and 50 controls underwent diffusion and resting-state functional magnetic resonance imaging (fMRI). White matter micro-structure and inter-hemispheric functional connectivity were quantified by fractional anisotropy (FA) and voxel-mirrored homotopic connectivity (VMHC). The CC was reconstructed by tractography and divided into five sub-regions. The associations of illness duration with FA of each CC sub-region and voxel-wise VMHC were examined using correlation analyses. Also, we investigated the potential relationship between illness duration, CC changes, and clinical variables using mediation analyses. RESULTS: In MDD patients, longer illness duration was selectively associated with lower FA of CC sub-regions 2 [partial correlation coefficient (pr) =–0.269, P=0.009] and 5 (pr=–0.296, P=0.004) as well as higher VMHC in the supplementary motor areas (pr=0.378, P

The advance speed of a longwall face is an essential factor affecting the mining pressure and overburden movement, and an effective approach for choosing a reasonable advance speed to realise coal mine safety and efficient production is needed. To clarify the influence of advance speed on the overburden movement law of a fully mechanised longwall face, a time-space subsidence model of overburden movement is established by the continuous medium analysis method. The movement law of overburden in terms of the advance speed is obtained, and mining stress characteristics at different advance speeds are reasonably explained. The theoretical results of this model are further verified by a physical simulation experiment. The results support the following conclusions. (i) With increasing advance speed of the longwall face, the first (periodic) rupture interval of the main roof and the key stratum increase, while the subsidence of the roof, the fracture angle and the rotation angle of the roof decrease. (ii) With increasing advance speed, the roof displacement range decreases gradually, and the influence range of the advance speed on the roof subsidence is 75 m behind the longwall face. (iii) An increase in the advance speed of the longwall face from 4.89 to 15.23 m/d (daily advancing of the longwall face) results in a 3.28% increase in the impact load caused by the sliding instability of the fractured rock of the main roof and a 5.79% decrease in the additional load caused by the rotation of the main roof, ultimately resulting in a 9.63% increase in the average dynamic load coefficient of the support. The roof subsidence model based on advance speed is proposed to provide theoretical support for rational mining design and mining-pressure-control early warning for a fully mechanised longwall face.

Myocardial remodelling is a common phenomenon in cardiovascular diseases, which threaten human health and the quality of life. Due to the lack of effective early diagnosis and treatment methods, the molecular mechanism of myocardial remodelling should be explored in depth. In this study, we observed the high expression of MBNL1 in cardiac tissue and peripheral blood of an isoproterenol (ISO)‐induced cardiac hypertrophy mouse model. MBNL1 promoted ISO‐induced cardiac hypertrophy and fibrosis by stabilizing Myocardin mRNA in vivo and in vitro. Meanwhile, an increase in MBNL1 may induce the apoptosis of cardiomyocytes treated with ISO via TNF‐α signalling. Interestingly, MBNL1 can be activated by p300 in cardiomyocytes treated with ISO. At last, Myocardin can reverse activate the expression of MBNL1. These results suggest that MBNL1 may be a potential target for the early diagnosis and clinical treatment of myocardial remodelling.

There is evidence that major depressive disorder (MDD) is related to serum lipid level alterations. However, the neural correlates underlying this association remain poorly understood. Forty-nine patients with MDD and fifty healthy controls (HCs) underwent structural, resting-state functional and diffusion magnetic resonance imaging scans. Voxel-based morphometry, functional connectivity (FC) and tract-based spatial statistics analyses were performed to assess brain structure and function, respectively. Blood samples were collected to measure serum levels of lipid variables including total cholesterol, triglyceride and high density lipoprotein cholesterol (HDL-C). Correlation and mediation analyses were conducted to investigate the associations of serum lipid levels with brain imaging measures in MDD patients and HCs, respectively. We found that the serum HDL-C level in MDD patients was lower than that in HCs. The lower serum HDL-C level was associated with lower gray matter volume (GMV) in ventromedial prefrontal cortex (VMPFC), higher within-network FC of the default mode network, and lower micro-structural integrity in multiple white matter regions in MDD patients. Moreover, the within-default mode network FC mediated the relationship between GMV in VMPFC and serum HDL-C level; white matter integrity in genu of corpus callosum mediated the relationship between serum HDL-C level and depressive symptom severity. However, we did not observe any correlations between serum lipids and brain imaging parameters in HCs. These findings help to identify neural correlates underlying the association between depression and serum HDL-C change, which may provide new insight into intervention, treatment and prevention of depression from the perspective of regulating serum lipids.

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.

Tendon injury is a common but tough medical problem. Unsatisfactory clinical results have been reported in tendon repair using mesenchymal stem cell (MSC) therapy, creating a need for a better strategy to induce MSCs to tenogenic differentiation. This study was designed to examine the effect of hypoxia on the tenogenic differentiation of different MSCs and their tenogenic differentiation capacities under hypoxia condition in vitro and to investigate the in vivo inductility of hypoxia in tenogenesis. Adipose tissue-derived MSCs (AMSCs) and bone marrow-derived MSCs (BMSCs) were isolated and characterized. The expression of hypoxia-induced factor-1 alpha (Hif-1α) was examined to confirm the establishment of hypoxia condition. qRT-PCR, western blot, and immunofluorescence staining were used to evaluate the expression of tendon-associated marker Col-1a1, Col-3a1, Dcn, and Tnmd in AMSCs and BMSCs under hypoxia condition, compared with Tgf-β1 induction. In vivo, a patellar tendon injury model was established. Normoxic and hypoxic BMSCs were cultured and implanted. Histological, biomechanical, and transmission electron microscopy analyses were performed to assess the improved healing effect of hypoxic BMSCs on tendon injury. Our in vitro results showed that hypoxia remarkably increased the expression of Hif-1α and that hypoxia not only promoted a significant increase in tenogenic markers in both AMSCs and BMSCs compared with the normoxia group but also showed higher inductility compared with Tgf-β1. In addition, hypoxic BMSCs exhibited higher potential of tenogenic differentiation than hypoxic AMSCs. Our in vivo results demonstrated that hypoxic BMSCs possessed better histological and biomechanical properties than normoxic BMSCs, as evidenced by histological scores, patellar tendon biomechanical parameters, and the range and average of collagen fibril diameters. These findings suggested that hypoxia may be a practical and reliable strategy to induce tenogenic differentiation of BMSCs for tendon repair and could enhance the effectiveness of MSCs therapy in treating tendon injury.

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

Background Lifelong premature ejaculation (LPE) has been linked to altered brain function and structure. Although the middle temporal gyrus (MTG) is consistently more affected in LPE, its functional and structural changes have yet to be determined at the subregional level. Aim To explore the functional and structural changes of MTG in LPE at the subregional level based on a combined analysis of multimodal magnetic resonance imaging data. Methods 25 patients with LPE and 21 healthy controls underwent resting-state functional and structural magnetic resonance imaging scans. The MTG was parcellated into the anterior part of the MTG (aMTG), middle part of the MTG, posterior part of the MTG, and sulcus part of the MTG. Resting-state functional connectivity (rsFC) and gray matter volume (GMV) of each MTG subregion were calculated and compared between the 2 groups. Outcomes The functional and structural changes of MTG at the subregional level were assessed in patients with LPE and controls, as well as the correlation of them with premature ejaculation diagnostic tool and Beck Depression Inventory. Results Despite similar rsFC patterns of each MTG subregion in both groups, quantitative comparison analyses revealed that patients with LPE showed increased rsFC between the left aMTG and the right cuneus (0.34 ± 0.12 vs 0.17 ± 0.17), between the right aMTG and the right parahippocampal gyrus (0.36 ± 0.16 vs 0.15 ± 0.10), and between the right middle MTG and the left MTG (0.40 ± 0.14 vs 0.18 ± 0.15) relative to controls (P .05, Bonferroni corrected). In addition, no significant correlations between rsFC and GMV of the MTG subregions and the clinical variables were found in patients with LPE (P > .05, Bonferroni corrected). Clinical Implications Functional hyperconnectivity in the MTG subregions may facilitate a more sophisticated understanding of the neuropathological mechanism underlying LPE. Strengths and Limitations There are no previous studies examining functional and structural changes in LPE at the MTG subregional level. The main limitation is the small sample size. Conclusions We present evidence that individuals with LPE have a selective functional hyperconnectivity yet preserved structural integrity in the MTG subregions, which may facilitate a more sophisticated understanding of the neuropathological mechanism underlying LPE by highlighting the critical role of the MTG in this disorder.

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.

Docetaxel (DTX)-based chemotherapy significantly eliminates rest cancerous cells and decreases the risk of death, thus remaining the mainstay of treatment for operable breast cancer (BCa). However, resistance or incomplete response to DTX occurs frequently, resulting in disease recurrence and poor prognosis. There is an urgent need to identify and understand the key factors and corresponding molecular bases driving this complicated pathogenesis. Herein, both data mining and profiling analysis using clinical BCa biopsies showed that expression levels of the nuclear receptor subfamily 2, group F, member 6 (NR2F6), a recently characterized central transcription factor for cancer immune surveillance, were significantly downregulated in DTX-resistant BCa. This downregulation, possibly regulated by leptin signaling, predicted a poor postoperative chemotherapy survival in DTX-resistant BCa. In both genetically engineered cell models and patient-derived xenograft models, we provided evidence that BCa cells with insufficient NR2F6 expression were less responsive to DTX treatment. Mechanistically, NR2F6 functioned as a potent corepressor of platelet-derived growth factor B receptor gene (PDGFRB) transcription by recruiting HDAC2 onto the PDGFRB promoter. Stable PDGFRB inhibition ameliorated NR2F6 deficiency-impaired response to DTX in BCa cells, indicating that NR2F6’s effect on DTX response is mediated, at least in part, through transcriptional repression of PDGFRB. Collectively, our findings define NR2F6 as an negative regulator of cell survival and DTX resistance, probably by serving as a convergent point linking leptin signaling and PDGF-B/PDGFRβ axis, in BCa cells.

Background Sleep disturbance is a common and key symptom that affects most of patients with major depressive disorder (MDD). However, neural substrates underlying sleep disturbance and their clinical relevance in depression remain unclear. Methods Ninety-six MDD patients underwent resting-state functional MRI. Fractional amplitude of low-frequency fluctuation (fALFF) and resting-state functional connectivity (rsFC) were used to measure brain function. Overnight polysomnography was performed to objectively measure sleep efficiency (SE), which was used to classify patients into normal sleep efficiency (NSE) and low sleep efficiency (LSE) groups. Between-group differences in fALFF and rsFC were examined using two-sample t-tests. Moreover, correlation and mediation analyses were conducted to test for potential associations between SE, brain functional changes, and clinical variables. Results LSE group showed decreased fALFF in right cuneus, thalamus, and middle temporal gyrus compared to NSE group. MDD patients with low SE also exhibited lower rsFC of right cuneus to right lateral temporal cortex, which was associated with more severe depression and anxiety symptoms. More importantly, mediation analyses revealed that the relationships between SE and severity of depression and anxiety symptoms were significantly mediated by the altered rsFC. In addition, these low SE-related brain functional alterations were not affected by antidepressant medication and were independent of structural changes. Limitations The lack of healthy controls because of “first-night effect”. Conclusion These findings not only may expand existing knowledge about neuropathology of sleep disturbance in depression, but also may inform real-world clinical practice by improving depression and anxiety symptoms through sleep regulation.

Cardiac hypertrophy is an early milestone of many heart diseases. LncRNAs often play a leading role in this process. However, its mechanism of action in cardiac hypertrophy has not been fully explained. In a previous study, we showed a new mode by which lncRNA-Mhrt inhibited cardiac hypertrophy by inhibiting myocardin. However, the underlying molecular mechanism remains unclear. This study aims to explore potential action modes of Mhrt in regulating the expression of myocardin in the process of cardiac hypertrophy. Here, we find that Mhrt reduces myocardin expression through KLF4 in vivo and in vitro. Meanwhile, Mhrt promotes the expression of KLF4 through direct binding to miR-145a-5p or inhibiting phosphorylation of KLF4 by forming a complex with KLF4 to prevent the binding of ERK and KLF4, thereby inhibiting myocardin expression and the development of myocardial hypertrophy. Taken together, our findings reveal a new pathway, Mhrt-KLF4-myocardin, that regulates cardiac hypertrophy and revealed additional possible action modes of Mhrt in the occurrence and development of cardiac hypertrophy. The new regulatory pathway serves as a potential therapeutic avenue for cardiac hypertrophy.

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.

Many dynamic disasters such as coal wall caving and roof falling have happened during longwall face crossing fault. Combined with the coal seam geological conditions in the 1302 longwall face AB coal mine, the paper comprehensively studies the overlying strata movement and the stress evolution laws of stope during superhigh-water material (SHWM) backfilling longwall face across fault by UDEC numerical simulation, theoretical analysis and on-site measurement. The results show that the stress during stable state is affected by the fault will increases abnormally. While the longwall face pass through the fault, the stress will abated and the vertical displacement of the overlying strata of two sides of the fault is significantly different. The fault significant blocks the propagation of stress and development of plastic zone. The superhigh-water material filling mining management roof has good protection effect on the roof when the longwall face encounters fault, which can effectively weaken the blocks effect of fault on stress propagation and plastic zone development. The numerical simulation results are consistent with the field experiments, and the research result provides theoretical basis and technical guidance for safe and efficient production during superhigh-water material backfilling longwall face through the fault.

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.

Understanding coal and rock permeability, and the corresponding influence on stress, is important in the field of energy development. In applied engineering, there is a tendency to employ three‐dimensional methods that are simpler, less time‐ and cost‐expensive, less computationally expensive, and larger scale. Thus, a numerical simulation fluid‐solid coupling method is proposed in this paper. The proposed numerical simulation method utilizes the stress‐permeability test results for elastic and plastic coal samples. The permeability models of the elastic and plastic coal samples under loading and unloading were obtained by fitting the experimental results and embedded them into FLAC3D software by using FISH language. The results of the uniaxial and triaxial flow simulations are consistent with the experimental results, thereby confirming the accuracy and feasibility of the numerical method proposed in this paper. This allows the permeability of the numerical reservoir model to be continuously updated according to the current stress level in the production process.

Background Sorafenib is one of the few effective first-line drugs approved for the treatment of advanced hepatocellular carcinoma (HCC). However, the development of drug resistance is common among individuals with HCC. Thus, there is an urgent need to solve this problem. Results Recent evidence indicated that the anticancer activity of sorafenib mainly relies on the induction of ferroptosis. In our study, genes that suppress ferroptosis, especially GPX4 and DHODH, were enriched in sorafenib-resistant cells and primary tissues and were associated with poor prognosis of HCC patients who received sorafenib treatment. Therefore, silencing GPX4 and DHODH might be a novel and effective strategy to overcome sorafenib resistance. Here, a novel ferroptosis inducer comprising a multiplex small interfering RNA (multi-siRNA) capable of simultaneously silencing GPX4 and DHODH was created. Then, exosomes with high multi-siRNA loading and HCC-specific targeting were established by fusing the SP94 peptide and the N-terminal RNA recognition motif (RRM) of U1-A with the exosomal membrane protein Lamp2b. The results from the in vitro and in vivo experiments indicate that this tumor-targeting nanodelivery system (ExoSP94−lamp2b−RRM-multi-siRNA) could enhance sorafenib-induced ferroptosis and overcome sorafenib resistance, which might open a new avenue for clinically overcoming sorafenib resistance. Conclusions We designed HCC-targeted exosomes (ExoSP94−Lamp2b−RRM) that can deliver a novel ferroptosis inducer. Our data show that ExoSP94−lamp2b−RRM-multi-siRNA could enhance sorafenib-induced ferroptosis by silencing GPX4 and DHODH expression and consequently increase HCC sensitivity to sorafenib. This is the first study to describe the use of engineered exosomes to overcome acquired sorafenib resistance with respect to ferroptosis.

Purpose: Alpha-adrenergic blockers are commonly used as a medical expulsive therapy (MET) for patients with ureteral calculi. The aim of this meta-analysis was to evaluate the efficacy and safety of alpha-adrenergic blockers compared with a placebo when used as a MET. Materials and methods: We carried out a systematic search of the PubMed, EMBASE, and Web of Science databases, and the Cochrane Library, for relevant articles from inception to November 2020. Our aim was to identify placebo-controlled trails in which patients were randomized to receive either alpha-adrenergic blockers (tamsulosin, alfuzosin, doxazosin, terazosin, naftopidil, or silodosin) or a placebo for the treatment of ureteral calculi. Results: According to strict inclusion criteria, database searches identified 8 placebo-controlled studies that included 2284 patients. Generally, α-blockers had no significant effect on the clearance of stones in the urinary tract (risk ratio [RR] = 1.05; 95% confidence interval [CI] = 1.00–1.11). However, subgroup analysis showed that α-blockers were effective in treating distal urinary tract stones (RR = 1.08; 95% CI = 1.02–1.15). With regards to adverse events, our analysis showed that the combination of MET with α-blockers was likely to cause dizziness (RR = 1.37; 95% CI = 1.06–1.79) and retrograde ejaculation (RR = 3.10; 95% CI = 1.81–5.29). Conclusion: Although α-blockers cannot improve the overall ureteral stone clearance rate, these drugs are still effective for the treatment of stones in the distal urinary tract. However, the application of α-blockers is likely to cause dizziness and/or retrograde ejaculation.

Background To observe the effects of vitamin D on the apoptotic human nucleus pulposus cells under tumor necrosis factor-α (TNF-α) treatment. Methods The gene expression data was downloaded from the NCBI Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE34095). Differentially expressed genes between degenerative disc and non-degenerative disc were performed by R software. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analyses were performed using The Database for Annotation, Visualization and Integrated Discovery (DAVID). Then, the human nucleus pulposus tissue was harvested from 12 patients according to the modified Pfirrmann classification and human nucleus pulposus cells were obtained from digestion of herniated nucleus pulposus tissue. The collected nucleus pulposus cells were treated with different concentration of TNF-α, and cellular apoptosis was measured by flow cytometry. Then, human nucleus pulposus cells were divided into following groups: normal culture medium, TNF-α treated, TNF-α, and vitamin D-treated groups. Cellular apoptosis rate was quantified by flow cytometry. Protein expression of p-p65, p65, and IkBa was detected with western blot analysis. Results A total of 536 differentially expressed genes were identified through bioinformatic analysis. KEGG pathway revealed that NF-kB signaling pathway was involved in the process of disc degeneration. In the NP cell cultures, vitamin D significantly increased cell proliferation potency. Furthermore, vitamin D inhibited TNF-α induced apoptosis of human nucleus pulposus cells. Vitamin D reduced the phospho-NF-κB/p65 expression in the TNF-α-treated NP cells. Conclusion Vitamin D can attenuate TNF-α-induced NP cells apoptosis through interfering with the NF-κB pathway.

High-dose chemotherapy followed by autologous stem cell transplantation (HDT-ASCT) is the standard of care for chemosensitive relapsed or refractory (R/R) aggressive B cell lymphoma. Patients with a positive positron emission tomography (PET) scan before ASCT have a poor prognosis, and those who fail to achieve a therapeutic response better than partial remission after salvage treatment are ineligible candidates for ASCT. We conducted this open-label single-arm prospective clinical study to evaluate the safety and efficacy of sequential infusion of CD19/22 chimeric antigen receptor (CAR) T cells following HDT-ASCT. Eligibility for this study included patients with R/R aggressive B cell non-Hodgkin lymphoma (B-NHL) with 18F-fluorodeoxyglucose-PET positivity and patients with stable or progressive disease after salvage chemotherapy. Between November 14, 2016, and August 15, 2019, 42 patients underwent HDT-ASCT followed by CD19/22 CAR T cell infusion. Grade 3 cytokine release syndrome (CRS) occurred in only 2 patients. Twenty-one percent of patients experienced any grade of neurotoxicity, 5% with severe grade 3. All cases of CRS and neurotoxicity were reversible. The overall response rate was 90.5% (95% confidence interval [CI], 77.4% to 97.3%). At a median follow-up of 24.3 months, the median progression-free survival (PFS) and overall survival were not reached. The 2-year PFS rate was 83.3 % (95% CI, 68.2% to 91.7%). No patients were found to be CD19- and CD22-negative at the time of progression; 97.1% and 68.6% of patients with ongoing complete remission (CR) had consistently detectable levels of CD19 and CD22 CAR transgene, respectively, at 3 months. The median time to onset of sustained B cell recovery was 8.2 months. The high durable CR rates and favorable safety profiles support the strong potential of the HDT-ASCT plus CD19/CD22 CAR T cell cocktail therapy for the suboptimal group of patients with R/R aggressive B-NHL who are less sensitive or fail salvage chemotherapy. These early data are encouraging and informative for future trials to further test the efficacy and safety of HDT-ASCT plus CAR T cell therapy in a larger population. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

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.

Heat-injection into coal seam has gained great attention as a supplementary method for the improvement of unconventional gas recovery from deep reservoirs in recent years. However, it involves a lot of ambiguous interactions among the deformation of formation, the transport of gas and the diffusion of heat in the porous coal media, especially the property of gas. In this paper, the seepage behavior of coal seam gas (CSG) that obeys non-Darcy flow law was directly observed in a conducted laboratory experiments. Then, a general Forchheimer equation was confirmed and strictly validated by the experimental data to characterize the non-Darcy seepage phenomenon. Subsequently, a fully coupled thermo-hydro-mechanical model was mathematically established. Based on the finite element approach, a numerical simulation for heat-injection enhanced coal seam gas recovery was then implemented. The susceptibilities of coal permeability and gas production to the gas sorption, heat-mass transfer, and the porosity-seepage characteristics of coal were quantified by a series of numerical scenarios. Final modeling and simulation results reveal that: (1) coal seam gas flow obeys non-Darcy law when the gradient of gas pressure is higher, but trends to be laminar flow that obeys Darcy law when the gradient is lower, and (2) heat-injection to stimulate coal seam could improve the production efficiency, increasing the Langmuir volume sorption parameter, the temperature correction coefficient and the initial values of permeability can improve coal permeability and enhance gas production.

Background: Previous studies have reported inconsistent findings regarding corticospinal tract (CST) changes in alcohol dependence. Here, we aimed to clarify this issue by examining the micro-structural integrity differences of distinct CST segments between alcohol-dependent patients and healthy controls. Methods: Diffusion tensor imaging was performed in a total of 39 male individuals, including 19 alcohol-dependent patients and 20 age-matched healthy controls. CST was reconstructed using tractography and was divided into inferior and superior segments at the level of the lateral sulcus. Multiple diffusion measures of each segment were compared between two groups. Results: For the bilateral whole CSTs, no diffusion measures showed significant between-group differences. However, compared to healthy controls, alcohol-dependent patients exhibited decreased FA and increased RD in the left-superior segment, increased FA and decreased RD/MD in the left-inferior segment, increased AD/MD in the right-superior segment, decreased RD/MD in the right-inferior segment. Conclusions: These findings suggest that CST impairments may vary with the fibre arrangement patterns of its segments in alcohol dependence. Keypoints We reconstructed the CST using tractography based on DTI data and divided the CST into different segments in order to explore more detailed micro-structural integrity changes in alcoholisms. Alcohol-dependent patients showed decreased RD and MD for the bilateral inferior segments of the CSTs. The left-superior segment exhibited decreased FA and increased RD while the right one exhibited increased AD and MD. These findings suggest that CST impairments may vary with the fiber arrangement patterns of its segments in alcohol dependence. In future work, more elaborate segmentation schemes and lager samples should be used to test the reproducibility of our findings.

In this paper, the temperature measurement accuracy of infrared thermal image under different emissivity is studied. Firstly, according to the formula of infrared temperature measurement, the influence of the object surface emissivity on the measurement accuracy of infrared thermal image is analyzed. The factors affecting the emissivity of the object are found. Secondly, the limitation of classical emissivity calculation method in infrared temperature measurement is explained. Thirdly, a model for improving the temperature accuracy of the non-steady state temperature field based on the emissivity of the infrared image is obtained, and the theoretical formula is obtained. Finally, three experiments of cast iron and stainless steel are carried out. The correctness and feasibility of this method is verified by the experimental results.

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.

Background Relapsed/refractory (R/R) multiple myeloma (MM) patients and primary plasma cell leukemia (PCL) have an unfavorable prognosis and no effective treatment. This study was designed to assess the safety and preliminary efficacy of a novel anti‐B‐cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cell in R/R MM and PCL. Methods Between February 22, 2017, and June 25, 2018, 28 R/R and two R/R primary PCL patients received a median dose of 11.2 × 106 CAR+ cells/kg. The subjects were refractory to a proteasome inhibitor and/or an immunomodulatory agent. Fludarabine and cyclophosphamide were given as lymphodepletion chemotherapy. Results Results for these 30 consecutive patients who received an anti‐BCMA CAR T cell infusion are reported. The patients had received a median of four prior lines of therapy. A total of 44 different types of adverse events were recorded, and hematologic toxic effects were the most common events of any grade during treatment. Hematologic toxic effects were also the most common events of grade 3 or higher. A total of 29 patients (96.7%) had cytokine release syndrome, which was of grade 1 or 2 in 24 patients (80%) and grade 3 in five patients (16.7%). Neurologic toxic effects only occurred in one patient (3.3%) and were of grade 1. The objective response rate was 90%, and the complete response rate was 43.3%. With a median follow‐up of 12.6 months, the median progression‐free survival (PFS) and overall survival were 5.2 months and 14.0 months. One of the two primary PCL achieved a complete response with a PFS of 307 days. The other patients achieved a very good partial response with a PFS of 117 days. Conclusions Anti‐BCMA CAR T cell treatment is safe and highly active in R/R multiple myeloma., We report the efficacy and safety of the infusion of anti‐BCMA CAR T cell treatment in with relapsed/refractory malignant plasma cell disease.Anti‐BCMA CAR T cell therapy exerted better safety and preliminary efficacy in relapsed/refractory multiple myeloma.Relapsed/refractory primary plasma cell leukemia may benefit from CAR T Cell treatment, although the duration of response is short.

Crocins, as a kind of water-soluble carotenoid pigment, are a series of ester compounds formed from crocetin and gentibiose or glucose, and mainly distributed among Crocus sativus L. (CSL), Gardenia jasminoides Ellis. (GJE). Crocins exhibit a wide range of pharmacological effects on neurodegeneration, cardiovascular disease, cerebrovascular disease, depression, liver disease, arthritis, tumor, diabetes, etc. This review systematically discussed the pharmacologic study of crocins in the aspect of structural characteristic and pharmacokinetics, and summarized the mechanism of treating disease. It summarized the abundant research of crocins from 1984 to 2020 based on the above aspects, which provide a reference for the deeply development and application of crocins.

In order to improve the resource training efficiency and login success rate of English online teaching assistant system, this paper proposes and designs an English online teaching assistant system based on deep learning. The overall structure of the system is designed in the web environment. The hardware of the system mainly includes the system login module, the homework function module and the examination information management module, so as to enhance the role of the system in English online teaching. In the software part of the system, convolution neural network in deep learning is used to train English online teaching resources to improve the quality of English online teaching resources. The experimental results show that, compared with the traditional system, the training efficiency and login success rate of the proposed method are improved, so the application performance of the designed system is strong.

BACKGROUND: Nucleic acids are potent stimulators of type I interferon (IFN-I) and antiviral defense, but may also promote pathological inflammation. A range of diseases are characterized by elevated IFN-I, including systemic lupus erythematosus (lupus). The DNA-activated cGAS-STING pathway is a major IFN-I-inducing pathway, and activation of signaling is dependent on trafficking of STING from the ER to the Golgi.METHODS: Here we used cell culture systems, a mouse lupus model, and material from lupus patients, to explore the mode of action of a STING antagonistic peptide, and its ability to modulate disease processes.FINDINGS: We report that the peptide ISD017 selectively inhibits all known down-stream activities of STING, including IFN-I, inflammatory cytokines, autophagy, and apoptosis. ISD017 blocks the essential trafficking of STING from the ER to Golgi through a mechanism dependent on the STING ER retention factor STIM1. Importantly, ISD017 blocks STING activity in vivo and ameliorates disease development in a mouse model for lupus. Finally, ISD017 treatment blocks pathological cytokine responses in cells from lupus patients with elevated IFN-I levels.INTERPRETATION: These data hold promise for beneficial use of STING-targeting therapy in lupus.FUNDING: The Novo Nordisk Foundation, The European Research Council, The Lundbeck Foundation, European Union under the Horizon 2020 Research, Deutsche Forschungsgemeinschaft, Chulalongkorn University.

Objective: This study tested wether preterm infants of ＜32 gestational weeks (GWs) with a blood gas derangement within 7days of life are at increased risk for moderate and severe bronchopulmonary dysplasia (BPD). Method: 236 preterm infants with ＜32 GWs from January of 2017 to December of 2019 were included in this study. First, univariate analysing determined wether there existed associations between BPD (moderate and severe) and blood gas values, clinical characteristics, interventions, daily given liquid and eneregy within 7days of life. Then multivarariate regession analysis was performed to know wether there were relationships between BPD (moderate and severe) and risk factors between which and BPD (moderate and severe) univariate analysing showed that P value was less than 0.1. Results: From univariate analysing, we found that PaO2, PaCO2 and HCO3 in 7th day of life, cesarean section (OR=0.508, 95%CI:0.275-0.94), getational age (GA, OR=0.163, 95%CI:0.077-0.344), birth weight (BW, OR=0.122, 95%CI:0.054-0.273), PDA (OR=2.839, 95%CI:1.1463-5.508), early onset infection (OR=3.00, 95%CI:1.483-6.069), and mechanical ventilation (MV, OR=4.562, 95%CI:2.405-8.653) were significantly associated with moderate and severe BPD. Because there existed close relationship between GA and BW (R=0.642, P=0.000) and BW dispersion was big in this group, we excluded BW in multivariate analysing. From multivariate analysing, besides GA (Exp (B)=0.176, 95%CI:0.08-0.389) , MV (Exp (B)=3.515, 95%CI:1.746-7.076), PaO2 (Exp (B)=0.468, 95%CI:0.226-0.969) in 7th day of life was the independent risk factor for moderate and severe BPD in the preterm infants of ＜32 GWs.Conclusion: Preterm infants of ＜32GWs with blood gas derangements within 7days of life could be at risk of moderate and severe BPD.

Numerous epigenetic alterations are observed in cancer cells, and dysregulation of mono-ubiquitination of histone H2B (H2Bub1) has often been linked to tumorigenesis. H2Bub1 is a dynamic post-translational histone modification associated with transcriptional elongation and DNA damage response. Histone H2B monoubiquitination occurs in the site of lysine 120, written predominantly by E3 ubiquitin ligases RNF20/RNF40 and deubiquitinated by ubiquitin specific peptidase 22 (USP22). RNF20/40 is often altered in the primary tumors including colorectal cancer, breast cancer, ovarian cancer, prostate cancer, and lung cancer, and the loss of H2Bub1 is usually associated with poor prognosis in tumor patients. The purpose of this review is to summarize the current knowledge of H2Bub1 in transcription, DNA damage response and primary tumors. This review also provides novel options for exploiting the potential therapeutic target H2Bub1 in personalized cancer therapy.

Edge computing extends the boundary of the cloud to the network edge, providing low latency and high bandwidth computing paradigm. Computation is trending to be offloaded to the edge to reduce service response time and energy consumption. In this paper, we propose Astraea, a novel AI service deployment platform that could automatically convert a raw AI model to RESTful web services at edge nodes. Experimental results show that a common AI model is able to be deployed at edge nodes in less than two minutes by Astraea, and gains 2Sx to up to 110x performance improvement compared to the traditional scheme.

The failure and design of coal pillars have always been the focus of research in the field of mining engineering, and there are often many water resources in goafs with rich aquifers. Under the influence of mining and long-term water invasion, it is easy to cause gradual failure and instability to coal pillars. Based on this, this paper proposes a numerical simulation method for the coupling of engineering scale mining-water invasion and a quantitative index of the damage ratio of coal pillars. The numerical parameters are calibrated with measurement data from coal-pillar stress. In the simulation process, the evolution of the strength, damage ratio, water pressure, stress, strain, and other parameters in coal pillars under the effect of mining-water invasion is realized, and the progressive failure mechanisms of coal pillars under mining-water immersion are revealed. On this basis, the effects of goaf water-level height and coal-pillar width on coal-pillar stability are quantitatively analyzed, and the critical goaf water-level height corresponding to different coal-pillar widths is obtained. Using the simulation results of this paper, the instability of a coal pillar in a coal mine is effectively solved, and the deformation of the coal-pillar rib and roof of the tailgate is reduced by 39.6% and 30.8%, respectively, which ensures the safe production of the longwall face.

Background: Previous neuroimaging studies have demonstrated brain abnormalities in patients with hepatic diseases. However, the identified liver–brain associations are largely limited to disease-affected populations, and the nature and extent of such relations in healthy subjects remain unclear. We hypothesized that serum liver function markers within a normal level would affect brain properties.Method: One hundred fifty-seven healthy young adults underwent structural, resting-state functional, and arterial spin labeling MRI scans. Gray matter volume (GMV), regional homogeneity (ReHo), and cerebral blood flow (CBF) analyses were performed to assess brain structure, function, and perfusion, respectively. Peripheral venous blood samples were collected to measure serum liver function markers. Correlation analyses were conducted to test potential associations between liver function markers and brain imaging parameters.Results: First, serum proteins showed relations to brain structure characterized by higher albumin associated with increased GMV in the parahippocampal gyrus and amygdala and lower globulin and a higher albumin/globulin ratio with increased GMV in the olfactory cortex and parahippocampal gyrus. Second, serum bilirubin was linked to brain function characterized by higher bilirubin associated with increased ReHo in the precuneus, middle cingulate gyrus, inferior parietal lobule, and supramarginal gyrus and decreased ReHo in the caudate nucleus. Third, serum alanine transaminase (ALT) was related to brain perfusion characterized by higher ALT associated with increased CBF in the superior frontal gyrus and decreased CBF in the middle occipital gyrus, angular gyrus, precuneus, and middle temporal gyrus. More importantly, we found that CBF in the superior frontal gyrus was a significant mediator of the association between serum ALT level and working memory performance.Conclusion: These findings may not only expand existing knowledge about the relationship between the liver and the brain but also have clinical implications for studying brain impairments secondary to liver diseases as well as providing potential neural targets for their diagnosis and treatment.

Tamoxifen remains the most effective treatment for estrogen receptor α (ERα)‐positive breast cancer. However, many patients still develop resistance to tamoxifen in association with metastatic recurrence, which presents a tremendous clinical challenge. To better understand tamoxifen resistance from the perspective of the tumor microenvironment, the whole microenvironment landscape is charted by single‐cell RNA sequencing and a new cancer‐associated fibroblast (CAF) subset, CD63+ CAFs, is identified that promotes tamoxifen resistance in breast cancer. Furthermore, it is discovered that CD63+ CAFs secrete exosomes rich in miR‐22, which can bind its targets, ERα and PTEN, to confer tamoxifen resistance on breast cancer cells. Additionally, it is found that the packaging of miR‐22 into CD63+ CAF‐derived exosomes is mediated by SFRS1. Furthermore, CD63 induces STAT3 activation to maintain the phenotype and function of CD63+ CAFs. Most importantly, the pharmacological blockade of CD63+ CAFs with a CD63‐neutralizing antibody or cRGD‐miR‐22‐sponge nanoparticles enhances the therapeutic effect of tamoxifen in breast cancer. In summary, the study reveals a novel subset of CD63+ CAFs that induces tamoxifen resistance in breast cancer via exosomal miR‐22, suggesting that CD63+ CAFs may be a novel therapeutic target to enhance tamoxifen sensitivity., Tamoxifen resistance is a severe clinical challenge in breast cancer treatment. In the present study, single‐cell RNA sequencing reveals a new subset of cancer‐associated fibroblast (CD63+ CAF) in the tumor microenvironment, which downregulates ERα and PTEN expression in breast cancer cells through exosomal miR‐22 and thus induces tamoxifen resistance.