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Amphibious vehicles, as a new type of aquatic and terrestrial transport platform, are increasingly involved in the existing transportation system. Resistance is a key factor that affects the efficiency and energy consumption of vehicles in aquatic sailing. Resistance reduction optimization design is a focal point and challenge in the design process of amphibious vehicles. In this paper, a resistance performance optimization method has been proposed based on neural networks and genetic algorithms. First, key parameters for the shape design are extracted based on a thorough understanding of the vehicle's performance. These parameters are used to construct a parameterized design space. Second, a training set is obtained based on the Latin hypercube sampling method and numerical calculation methods, and a test set is randomly generated. To achieve better resistance prediction performance, a method based on the genetic algorithm-optimized backpropagation Neural Network is proposed. Next, the resistance performance of the two operating conditions is optimized through the non-dominated sorting genetic algorithm II, and optimized configuration parameters are obtained, which has a 22.71% energy-saving ratio at cruising speed. Finally, the optimized configuration is analyzed using numerical calculation methods to validate the resistance prediction and optimization methods. [ABSTRACT FROM AUTHOR]

Amphibious transport vehicles have increasingly become an important tool for connecting water and land transportation, serving both water and land transport missions. However, due to the unique shape of amphibious vehicles, their sailing resistance is high, which severely restricts their widespread use. In this paper, a deformable trimaran amphibious transport vehicle with retractable side hulls is designed. Based on the Reynolds-averaged Navier–Stokes equation, a resistance prediction method for amphibious vehicles is established and verified through towing experiments. The resistance characteristic of the trimaran vehicle is studied and optimized. First, the effects of the side hull and its position on resistance performance are analyzed, and the sensitivity of position parameters is evaluated. Then, the bow plate angle on resistance is analyzed. Finally, a surrogate model of the side hull position parameters and the bow plate angle with resistance is established using the Kriging method. The Particle Swarm Optimization is used to search for the minimum resistance configuration Opt 2, which achieves a drag reduction effect of 19.84% at the design speed. [ABSTRACT FROM AUTHOR]

The main focus of this paper is the amphibious vehicle's water-land trans-media capability, specifically its ability to efficiently carry out transportation tasks in rivers and nearshore areas. This capability relies on three key processes: launching, water exiting, and river crossing. To study these processes, hydrodynamic numerical simulations are conducted. The Reynolds-averaged Navier–Stokes) equation, simplified terra mechanics model, and body force method are adopted to analyze the trans-media and self-propulsion processes. Results indicate that the optimal launching speed is around 15 km/h, with a stable trim and heave, and a launching angle range of 15°–25° for insubmersibility and stability. Furthermore, high-speed water exiting enhances insubmersibility and imposes lower requirements on road adhesion conditions, outperforming low-speed water exiting. In terms of self-propelled river crossing, higher heading angles and faster river currents improve hydrodynamic lift, with the fastest crossing achieved at a 10° heading angle for a current speed of 2.5 m/s and a forward speed of 30 km/h. [ABSTRACT FROM AUTHOR]

When a tunnel boring machine (TBM) excavates in the mudstone layer, the slacking mudstone will be formed under the action of the disc cutter due to the argillization effect. Therefore, the cutter wear mechanism differs significantly from that in the hard rock layer, and the hazard of flat wear increases rapidly. To predict the cutter wear in the mudstone, a novel prediction model based on the "mixture lubrication-cavity expansion" theory is established in the present study, which takes the argillization effect into consideration. Initially, the cutter wear mechanism in the mudstone was revealed by the mixture lubrication theory. Then a modified cavity expansion model was proposed and the thickness of the slacking mudstone in the rock was determined. Subsequently, according to the force acting on the disc cutter, the motion of disc cutter during the rock breakage process, and the critical condition for flat wear, formulas for the normal and flat wear of a disc cutter considering the argillization effect were derived. Finally, the proposed model was employed to predict the wear loss of a disc cutter in a tunnel project in Chongqing. The effectiveness of the proposed model was verified. It was found that the force acting on the disc cutter is borne by the slacking mudstone and the cutter simultaneously. In the modified cavity expansion model, the zone of the rock beneath the cutter is divided into the core zone (0 ≤ r ≤ T/2), argillization zone (T/2 ≤ r ≤ ra), plastic zone (ra ≤ r ≤ rp), and elastic zone (r ≥ rp). The stress caused by the cutter is equal to the stress at the argillization zone. The argillization effect can reduce the wear loss to some extent due to the mixture lubrication, however, it aggravates the risk of flat wear. This study will enrich the understanding of the cutter wear mechanism during the tunneling. Furthermore, it will provide some references for the design of the TBM and the scheme of the tunneling project. [ABSTRACT FROM AUTHOR]

Research on the resistance and maneuvering characteristics is a key requirement in amphibious vehicle design to ensure safety and efficiency. To tackle the challenges of evaluating amphibious vehicles' hydrodynamic performance, as well as the lack of research and systematic approaches, a comprehensive performance evaluation method based on the RANS method and MMG model is introduced in this study, and the influence of a stern hydrofoil is evaluated. Firstly, the numerical calculation model is established based on the RANS method and validated by towing tests. The resistance characteristics of vehicles with and without stern hydrofoil are evaluated. The hydrofoil has a 9.37% drag reduction rate under the rated condition. Then, the static drift tests, circular motion tests, and static heel tests are simulated to obtain vehicles' hydrodynamic coefficients. Subsequently, the four-degree-of-freedom MMG models are established to predict the vehicles' maneuvering performance and evaluate the effect of stern hydrofoil. The results obtained from CFD and predictions are compared, confirming the capability of the MMG model. The stern hydrofoil can improve turning performance but affects course-keeping and yaw-checking abilities. • An amphibious vehicle's resistance and maneuvering characteristics are investigated. • The RANS method and towing tests are adopted for hydrodynamic analysis. • A 4 DOF MMG model is established to analyze the maneuvering performance. • Stern hydrofoil has a drag reduction effect of 9.37% at cruising speed. • Stern hydrofoil improves turning performance but hurts course-keeping and yaw-checking ability. [ABSTRACT FROM AUTHOR]

Argillization is a process in which clay-bearing rocks disintegrate into the clay under the action of high temperature, pressure, and water. When tunnel boring machines (TBMs) excavate in the mudstone, argillization takes place, causing the clogging of the TBM cutterhead. As a result, the penetration rate drops gradually. Abnormal wear might occur. To investigate the evolution of argillization of mudstone and cutter wear during the TBM tunnelling, a series of rotary indentation tests were carried out on the self-designed experimental bench for different loading times. During the test, the temperature and penetration depth of disc cutters were measured in real time. After loading, microstructures of cutting grooves, slacking mudstone, and worn cutter ring were observed by stereomicroscope. Consequently, the evolution of argillization in mudstone and cutter wear were investigated. Experimental results indicate that the argillization process of mudstone by disc cutter can be divided into three stages: mechanical cutting stage, deterioration of mudstone and the formation of slacking mudstone stage, and adherence of slacking mudstone stage. Specifically, at mechanical cutting stage, the rock was cut by cutter directly, causing high frictional heat. Then the microstructure of mudstone was deteriorated due to the water-weakening mechanisms, temperature effect, and mechanical activation effect. Finally, the slacking mudstone was adhered to the disc cutter. Correspondingly, due to the argillization of mudstone, the disc cutter wear goes through the mechanical wear stage, argillization wear stage, and secondary wear stage in sequence. This investigation reveals the rock cutting mechanism of TBM considering the argillization of mudstone. Furthermore, it provides some references for design and operation of the TBM. [ABSTRACT FROM AUTHOR]

Background: With widespread clinical application of imaging techniques, renal space-occupying lesions have been identified at an increasing frequency. Here, we report two rare cases, Castleman disease (CD) and IgG4-related disease (IgG4-RD), presenting primarily with the symptoms and imaging findings of kidney malignancy. Case presentation: In case 1, an occupying lesion located in the right renal pelvis was detected using magnetic resonance imaging in a 32-year-old female who presented with hematuria and lumbago. First misdiagnosed as carcinoma of the renal pelvis, the patient underwent right radical nephroureterectomy. However, postoperative pathological and immunohistochemistry studies finally confirmed the diagnosis of CD. In case 2, a 45-year-old male presented with the chief complaint of anuria. Nephrostomy and renal biopsy indicated lymphoma, following which, antegrade urography and computed tomography urography were performed, which revealed bilateral hydronephrosis and mass lesions around the renal pelvis. Partial resection of the masses and frozen section examination indicated the diagnosis of CD. However, the results of postoperative histopathology and immunohistochemistry combined with serum IgG4 were consistent with IgG4-RD. Both the patients recovered well after drug treatment without recurrence of the diseases. Conclusions: Inflammatory pseudotumor of CD and IgG4-RD with kidney involvement are primarily diagnosed by postoperative histopathology and can pose a preoperative diagnostic challenge because these lesions can masquerade as kidney malignancy. Therefore, we recommend core biopsy as a nonnegligible procedure to evaluate renal masses and potentially prevent unnecessary surgical treatment. [ABSTRACT FROM AUTHOR]

Background: In recent years, long non-coding RNAs (lncRNAs) have attracted much attention because of its regulatory role in occurrence and progression of tumors, including triple-negative breast cancer (TNBC). LncRNA PITPNA antisense RNA 1 (PITPNA-AS1) has been explored in some cancers, whereas its function and molecular mechanism in TNBC remain unclear.Methods: PITPNA-AS1 expression in TNBC tissues and cells was determined by RT-qPCR. TNBC cell viability, proliferation, migration, invasion were assessed with CCK-8, colony formation, wound healing, transwell assays. Cell apoptosis was evaluated by flow cytometry. Expression of EMT-related markers was detected by western blot analyses. The molecular mechanism of PITPNA-AS1 was explored by RNA pull down, luciferase reporter, RIP and ChIP assays.Results: PITPNA-AS1 showed high expression levels in TNBC tissues and cells. PITPNA-AS1 knockdown suppressed TNBC cell viability, proliferation, migration, invasion in vitro and inhibited xenograft tumor growth in mice. Mechanistically, PITPNA-AS1 upregulated SIK2 expression by sponging miR-520d-5p and recruiting DDX54 protein. Results of rescue assays suggested that the inhibitive effects of silenced PITPNA-AS1 on TNBC cellular processes were partially rescued by overexpressing SIK2 or combination of miR-520d-5p inhibition and DDX54 overexpression. More importantly, we found that the upregulation of PITPNA-AS1 in TNBC cells was attributed to transcription factor MYBL2.Conclusion: PITPNA-AS1 activated by MYBL2 plays an oncogenic role in TNBC through upregulating SIK2. [ABSTRACT FROM AUTHOR]

Keywords: Joint orientation; Indentation tests; Performance; Rock breakage processes; Cutting efficiency EN Joint orientation Indentation tests Performance Rock breakage processes Cutting efficiency 2087 2108 22 03/30/21 20210401 NES 210401 Introduction In the last few decades, tunnel boring machines (TBMs) have widely been employed in civil and hydraulic engineering for their good applicability (Adoko et al. [1]; Hassanpour et al. [18]; Liu et al. [26]; Yagiz [41]; Yagiz and Karahan [44], [45]). By comparison, it is found that the rock breakage modes in the experiment are similar with numerical simulations by Jiang et al. ([20]), in which the rock breakage process of jointed rock under two cutters was modeled by distinct element method. Furthermore, to investigate the combined effects of joint spacing and orientation on the rock breakage process, Bejari and Khademi Hamidi ([6]) carried out a series of rock indentation tests by two disc cutters through the discrete element method. [Extracted from the article]

The accurate prediction of disc-cutter wear has been a longstanding topic that affects the tunneling efficiency and performance of tunnel boring machines, especially the prediction of flat wear extent in mixed ground. In the present study, a novel method for predicting the wear depth of the disc cutter is proposed based on energy analysis. Initially, the critical condition for the occurrence of normal and flat wear is determined. Subsequently, according to the geometry of disc cutters and the relationship between wear loss and friction work, the normal and flat wear depth of the disc cutter are obtained, respectively. By comparing calculated wear with Ren's prediction model and a case study, the effectiveness of the present model was verified. Finally, the influences of penetration depth and installation radius on cutter wear in mixed ground were analyzed. The research results indicate that the critical condition for the occurrence of flat wear is that the resistance moments acting on disc cutters exceed the driving moment. In addition, it was found that flat wear extent was much larger than the normal one. The disc cutter is prone to wear abnormally in mixed ground. Sensitivity analyses on penetration depth and installation radius show that wear from of disc cutters is determined by penetration depth. Furthermore, both normal and flat wear exert positive correlations with installation radius. The present work may provide some primary understanding about the determination of the critical condition for the occurrence of flat wear under different engineering environments. [ABSTRACT FROM AUTHOR]

Argillization is commonly observed as excavating in mudstone stratum by tunnel boring machine. In addition to the operational and geological parameters studied by previous researchers, this phenomenon also has significant influence on the performance of tunnel boring machine, such as penetrate rate, advance rate, and utilization rate. In general, water is a key factor affecting the progress of argillization. With the aim to investigate the effect of water content on argillization of mudstone during the tunnelling, a new rolling abrasion test was conducted on rock blocks with moisture contents of 2.82%, 3.44%, 4.79%, 6.06%, and 6.75%. In the experiment, penetration depth, temperature fields of disc cutter and rock blocks, and wear loss of cutters were recorded. In addition, the microstructures of cutting groove on rock blocks and slacking mudstone were observed by OLYMPUS SZX16 stereomicroscope. According to experimental results, three stages of argillization process can be divided: (1) water evaporation of mudstone nearby the disc cutter, (2) destruction of microstructure of mudstone, and (3) formation of slaking mudstone. Uneven shrink, water-weakening effects, temperature effects, and mechanical activation are mainly contributed to the damage of microstructures of rock blocks. In addition, the variation in water content accelerates the argillization process. By comparison, it is found that wear loss of disc cutter and cutting efficiency show negative and positive correlation with the extent of argillization, respectively. However, flat wear appears due to the argillization. Therefore, in engineering practice, to obtain high work efficiency of tunnel boring machine, it is necessary to keep water content of clay-bearing rock in a reasonable range. This study reveals the argillization process and abnormal cutter wear mechanism from the microstructure's perspective. In addition, the effects of temperature, water, and mechanical motion are simultaneously taken into consideration. The present study provides some references for reasonably improving tunnel boring machine performance in the tunnel construction. [ABSTRACT FROM AUTHOR]

Amphibious vehicles are capable of moving on both water and land, which makes their design more complex than that of ships. The locomotion mechanism of an amphibious vehicle is the main distinguishing feature from ships and is also the primary source of water resistance. The resistance characteristics of amphibious vehicles with different locomotion mechanisms are mainly studied in this paper. Firstly, a numerical calculation method based on the RANS method is established and verified by experiments. Secondly, the resistance characteristics of the amphibious vehicle under a series of speeds are analyzed, and the importance of reducing pressure resistance is demonstrated. Then, the resistance characteristics of different amphibious vehicle configurations are compared. Hull 1 has the smallest resistance at low speed, with a maximum resistance reduction rate of 9.3%; Hull 3 has the best performance at high speed, with a maximum resistance reduction rate of 12.5%. The influence of different configurations is analyzed from the perspectives of the flow field, vehicle attitude, and pressure distribution. Finally, the resistance values and their proportion of total resistance acting on different locomotion mechanisms are analyzed. The results show that the resistance at low speed is related to the complexity of the surface, and the resistance at high speed is more dependent on the attitude. The conclusions of this study have guiding significance for the design of high-speed amphibious vehicles. • The hydrodynamic characteristic of a high-speed amphibious vehicle is investigated. • The resistance characteristics of different locomotion mechanisms are studied. • Hull 1 and Hull 3 perform best at low and high speeds, respectively. • The locomotion mechanism resistance mainly depends on its surface complexity at low speeds. • The attitude and flow field characteristics determine the high-speed performance. [ABSTRACT FROM AUTHOR]

The resistance reduction optimal design of amphibious vehicles is essential to improve efficiency and reduce energy consumption. In this paper, the hydrodynamic characteristics of an amphibious transport vehicle are investigated by Computational Fluid Dynamics (CFD) method based on the Reynolds-averaged Navier-Stokes (RANS) solver. A set of towing tests are conducted to verify grid independence and computational accuracy. Four typical shape control parameters are selected as optimal design variables and the independent effects of each variable are analyzed. The sample set is obtained using Latin Hypercube Sampling (LHS), and corresponding three-dimensional models are generated based on the parameters of each sample point. CFD calculations are then used to obtain the resistance characteristics of the models. The Kriging method is utilized to establish an approximate model, and the credibility of the model is verified. The Non-Dominated Sorting Genetic Algorithm-II (NSGA-II) is used to find a global optimal solution or set based on approximate models. Two optimized configurations, Opt1 and Opt2, are obtained, corresponding to single- and multi-objective optimization results, respectively. At the design speed of the amphibious transport vehicle, Opt1 has the highest resistance reduction rate of 12.7907% under the full load condition, while Opt2 has resistance reduction rates of 11.0863% and 8.5293% with and without load, respectively. [Display omitted] • The resistance characteristic of an amphibious transport vehicle is investigated. • The RANS method is adopted for resistance prediction. • Kriging approximation models are established based on LHS. • NSGA-II method is used for the optimal design. • The optimized models have significant improvements in resistance. [ABSTRACT FROM AUTHOR]

Interstitial cystitis (IC) is a bladder syndrome characterized by pelvic pain and urinary frequency without infection or other identifiable pathology. There are no effective treatments to cure IC. This study investigated the effects of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) injection on IC rat model. Furthermore, we used a coculture system to find the possible molecular mechanism on the human uroepithelial cells (SV-HUC-1), which was the cell model of IC. A rat model of IC was established via systemic injection with cyclophosphamide (CYP) and a cell model of IC was induced by being exposed to tumor necrosis factor (TNF)-α (10 ng/ml). After one week, UC-MSCs injection significantly ameliorated the bladder voiding function in IC rat model. And the Histo- and immunohistochemical analyses showed that UC-MSCs can repair impaired bladder, reduce mast cell infiltration and inhibit apoptosis of urothelium. ELISA results showed that UC-MSCs can decrease IL-1β, IL-6 and TNF-α in bladder. In the coculture system, UC-MSCs can promote proliferation of impaired SV-HUC-1 cells, and inhibit apoptosis. However, while knocked down EGF secreted by UC-MSCs with siRNA, the effects would be weaken. Western blot showed that UC-MSCs increase protein expression levels of p-AKT and p-mTOR in SV-HUC-1 cells, and decrease the levels of cleaved caspase-3. Taken together, we provide evidence that UC-MSCs therapy can successfully alleviate IC in a preclinical animal Model and cell model by alleviating inflammation, promoting proliferation and inhibiting apoptosis. In addition, we demonstrate that the AKT/mTOR signaling pathway was activated. [ABSTRACT FROM AUTHOR]

Amphibious tractors are capable of towing loads over land and water, which will save time effectively and reduce the cost of transport between water and land. Due to their smaller displacement and more fragile stability, the hydrodynamic characteristics of amphibious tractors are quite different from those of tugboats. The towing position will significantly impact the attitude and resistance characteristics of the vehicle. In this paper, the towing position of a light amphibious tractor is thoroughly investigated, in order to improve hydrodynamic characteristics and reduce energy consumption of vehicles. First of all, the towing force effect is researched based on the force equilibrium model. Secondly, a numerical model is established referring to the Reynolds Averaged Navier-Stokes method, which is validated by towing experiments. Moreover, various towing position forms are evaluated to research the towing effects and working principles. Eventually, a coupled model of pitch and heave motion is established to investigate the dynamic response in the longitudinal plane. Results indicate that towing positions at the rear of the vehicle, combined with low height, are conducive to the hydrodynamic performance of amphibious tractors. • The hydrodynamic characteristic of an amphibious tractor is investigated. • The effects of longitudinal and vertical towing positions are studied. • Towing force position significantly affects the resistance, trim, and stability. • Lowing the towing position can improve the trim and resistance characteristics. • Setting the towing force at the rear can improve the initial stability and seakeeping. [ABSTRACT FROM AUTHOR]

A numerical approach is established to study the hydrodynamic performance using an amphibious transport vehicle (ATV) as a research object. Numerical calculation based on the Reynolds average Navier–Stokes method is studied in terms of first layer grid height, surface meshing partition scale, and prismatic layer coefficient. Through uncertainty analysis, the correctness and convergence of the numerical approach are verified. Towing tests are conducted to compare the experimental data with the simulation results, which validated the reliability of the numerical approach under all working conditions. Results show that the numerical approach will affect the simulated results, with an average error of 3.91% for the resistance and 4.21% for the trim, meeting the requirements for analysis accuracy. Based on the proposed numerical approach, an optimization design is carried out to improve the hydrodynamic performance of the ATV. Effects of bow plate angle, stern flap angle, and stern flap install height are studied. Latin hypercube is used for sampling in optimization design, and the Kriging method is applied to establish an approximate model. The cross-validation is carried out using the leave-one-out method. Particle swarm optimization is used for parameter optimization, and the optimized configuration is verified using the numerical approach. Results indicate that the combination of bow plate and stern flap shows excellent improvement in the hydrodynamic performance of amphibious vehicles. Numerical error of the approximate model is only 0.292%, which fully verifies its accuracy and effectiveness. The optimized ATV configuration shows the best drag reduction performance of 38.81% compared to the original model. [ABSTRACT FROM AUTHOR]

Although aberrant expression of peroxidasin-like (PXDNL) has been associated with carcinogenesis, its potential role in the Urothelial Carcinoma of the Bladder (UCB) remains unknown. The present study aimed to explore the role of PXDNL in UCB carcinogenesis and its potential clinical value. Based on The Cancer Genome Atlas (TCGA) data, bioinformatics was used to explore the potential clinical value of PXDNL. Wound healing and Transwell invasion assays were employed for the purpose of assessing the cell motility, while the Western Blotting experiments were utilized for investigating the protein expression pattern of PXDNL in UCB and investigating the Epithelial-to-Mesenchymal Transition (EMT) and Wnt/β-catenin pathways for understanding the probable mechanisms involved. PXDNL mRNA was overexpressed in UCB tissues and indicated a poor prognosis. High PXDNL mRNA levels were also associated with advanced clinicopathological features and were regarded as independent prognostic factors for UCB. However, PXDNL showed a weak correlation with immune cell infiltration in UCB. In addition, the findings of the study verified that the existing form of the PXDNL protein was 57-kDa and it was upregulated in the UCB cell lines and tissue samples. Furthermore, silencing PXDNL inhibited, while overexpressing PXDNL promoted EMT and motility of UCB cells in vitro. Mechanistic studies showed that PXDNL activated UCB cell motility via the Wnt/β-catenin pathway. The results reveal a novel molecular target that could be further explored for developing preventive, predictive, and individualized treatment strategies for UCB. [ABSTRACT FROM AUTHOR]

The shipping industry is one of the crucial sources of carbon emissions. With carrying capacity both on land and water, the hydrodynamic characteristics of amphibious vehicles are essential indicators of energy saving and emission reduction. The hydrodynamic characteristics of an amphibious vehicle driven by a single waterjet propulsion are investigated in this study, together with the impact of the NACA0012 hydrofoil mounted at the bow and stern. Based on the RANS and body force methods, the hydrodynamic calculation models of the bare hull and waterjet-driven hull are established. All CFD calculations are based on STAR-CCM+. Based on the towing experiment, an uncertainty analysis is conducted to confirm the precision and legitimacy of the numerical calculation approach. The thrust deduction characteristics of vehicle hulls with different hydrofoil models are analyzed respectively. Small or negative thrust deductions always occur at medium and high speeds. Combined with the analysis of vehicle attitude, flow field, and pressure distribution, the inherent thrust deduction characteristics of the amphibious vehicle and the influence of hydrofoils are studied. Then, the hydrodynamic characteristics of different configurations are compared. The lift characteristics of hydrofoils and their influence on the vehicle's attitude and resistance are studied. The change in the performance of the stern hydrofoil caused by the waterjet propulsion is analyzed. Results show that the hull with two hydrofoils has the best drag-reduction effect when F r < 1.43 , and the highest drag-reduction rate is 25.7%. [Display omitted] • The interference of hydrofoils on amphibious vehicles is avoided through the mechanism design. • The RANS method and body force method are used to study the influence of hydrofoils. • The stern hydrofoil reduces the peak resistance but extends the transition state of the amphibious vehicle. • The hull combined with two hydrofoils has the best drag-reduction effect when F r < 1.43 , highest rate is 25.7%. • The suction of the waterjet propulsion can increase the lift on the stern hydrofoil. [ABSTRACT FROM AUTHOR]

Objective To examine whether adding a sexual dysfunction domain to urinary, psychosocial, organ specific, infection, neurologic or systemic, and tenderness (UPOINT) system improves the association with interstitial cystitis and bladder pain syndrome (IC-BPS) symptom severity due to a high prevalence of sexual dysfunction in women. Methods A total of 90 Chinese women with IC-BPS were prospectively collected and classified in each domain of the UPOINT system. Symptom severity was measured using the Interstitial Cystitis Symptom Index (ICSI). The sexual function was evaluated using the Female Sexual Function Index (FSFI). Clinically relevant associations were calculated. Results The percentage of patients positive for each domain were 90 of 90 (100%), 33 of 90 (37%), 88 of 90 (98%), 21 of 90 (23%), 36 of 90 (40%), 38 of 90 (42%), 62 of 90 (69%) for the urinary, psychosocial, organ specific, infection, neurologic or systemic, tenderness, and sexual dysfunction, respectively. There were significant associations between the number of domains and ICSI (Spearman r = 0.386; P <.05) and FSFI (Spearman r = 0.614; P <.001) scores. After adding a sexual dysfunction domain to create a modified UPOINTS system, the association between the number of domains and symptom severity was improved (correlation coefficient r changed from 0.386 to 0.572; P <.001). The presence of sexual dysfunction had a significant impact on the ICSI scores ( P = .032), pain scores ( P = .042), and quality of life index scores ( P = .035). Significantly reduced FSFI scores were found in patients who had positive psychosocial, organ specific, and tenderness domains (all P values <.05). Conclusion Our study demonstrated sexual dysfunction was an important component of IC-BPS phenotype, and adding a sexual dysfunction domain to the UPOINT system improved the association with IC-BPS symptom severity. [ABSTRACT FROM AUTHOR]

The damage and deterioration of jointed rock mass under dry-wet cycling strongly influence the rock fracture characteristics, which threaten the safety of reservoir bank slopes. To explore the effect of dry-wet cycling on the mechanical properties of jointed rock, in the present study, a sequence of uniaxial compression tests were conducted on the jointed sandstone subject to the dry-wet cycles. The deformation and cracking process were quantitatively studied by the digital image correlation (DIC) system. Subsequently, four failure modes after the dry-wet cycles were found. Finally, a rock fracture criterion that considers the effect of dry-wet cycling is established based on the Drucker-Prager criterion. The results show that the compressive strength, elastic modulus, and crack initiation stress level of the jointed rock samples gradually decreased with increasing dry-wet cycle number. Dry-wet cycling aggravated the localized deformation of the jointed sandstone samples prior to failure and drastically reduced the damage degree during failure. The experiments highlight four main failure modes of jointed rock subjected to dry-wet cycling: tensile failure; mixed shear-tensile failure; buckling-shear failure; and mixed buckling-shear-tensile failure. The fracture toughness calculated using the dry-wet cycle fracture criterion is consistent with that obtained from the fracture test. The established fracture criterion can consequently be applied to estimate the fracture toughness of rock under dry-wet action. This study provides important guidance for the stability analysis of slope rock mass and preventing geological disasters in reservoir bank slopes. [ABSTRACT FROM AUTHOR]

A geometry‐constraint‐based nonordinary state‐based peridynamic (GC‐NOSBPD) model is developed to investigate the fracture characteristics of flawed brittle disc specimens under compressive loading as well as its fracturing mechanism. The bond‐associated horizon (BAH) size is directly defined based on the kinematic constraint (KC). This proposed model can well mitigate the numerical oscillation. The failure criteria based on the bond‐associated stress state are utilized to simulate the fracture of materials. Two stress effects can offer an insight into the fracturing mechanism of flawed specimens. The failure modes of flawed specimens are controlled by the tensile failure, and the crack growth trajectories acquired by the present numerical model are equivalent to those obtained by the experimental observations. The effects of size and crack inclination angles on the fracture toughness of brittle materials are assessed. The GC‐NOSBPD model is competent for evaluating the fracture damage of flawed brittle materials and understanding its failure mechanism. [ABSTRACT FROM AUTHOR]

To explore the relationship between serum estrogen levels and urinary incontinence in a nationally representative female population. We included women who had serum estradiol measurements and self-reported urinary incontinence problems in the 2013-2016 National Health and Nutrition Examination Survey cycles. A weighted multivariable logistic regression model was used to determine the association between urinary incontinence and serum estrogen levels after adjusting for age, race, Body Mass Index, diabetes, venipuncture, hypertension, poverty-to-income ratio, smoking, marital status, alcohol use, education, and menopause. A total of 4114 individuals were ultimately included in our study. Of these women, 1200 (29.17%) complained of urge urinary incontinence (UUI), 1674 (40.69%) complained of stress urinary incontinence (SUI), 730 (17.74%) complained of mixed urinary incontinence (MUI). Women in the lowest quartile of serum estrogen were more likely to complain of UUI compared to those in the highest quartile (OR = 1.885; 95% CI = 1.042-3.412, P =.039). No association was noted between serum estrogen levels and SUI or MUI. Our study shows a significant association between low serum estrogen level and the increased likelihood of UUI in women. Further research is required to validate our findings, elucidate the physiological mechanisms that underlie them, and assess potential therapeutic implications. [ABSTRACT FROM AUTHOR]

In case of earthquakes and crustal movement, the concentration of impounding load over a large region of crust can cause disturbances to the stratum. In order to quantitatively investigate crack initiation, propagation and coalescence processes of jointed stratum based on thermal variations caused by concentrated load, a series of indentation tests were performed on jointed granite specimens, failure process was respectively recorded by synchronized digital image correlation system and infrared camera. Then, strain and infrared radiation temperature of mixed shear-tensile and tensile conical crack were analyzed. In the initiation process, experimental results indicate that the abnormities in the temperature concentration factors are caused by the frictional-thermal effect for mixed mode crack and the thermoelastic effect for tensile mode crack. Subsequently, in the propagation process, these two cracking types followed newly proposed criteria, namely, the maximum temperature gradient criterion for mixed mode crack and the minimum temperature gradient criterion for tensile mode crack. In addition, the intensity of temperature concentrations in crack initiation stage and coalescence stage are more pronounced than that of crack propagation stage. The new findings from the infrared radiation temperature distributions provide some fundamental references for geophysical prospecting in jointed rock mass. [ABSTRACT FROM AUTHOR]

Aims. Notch1 signaling regulates microglia activation, which promotes neuroinflammation. Neuroinflammation plays an essential role in various kinds of pain sensation, including bladder-related pain in bladder pain syndrome/interstitial cystitis (BPS/IC). However, the impact of Notch1 signaling on mechanical allodynia in cyclophosphamide- (CYP-) induced cystitis is unclear. This study is aimed at determining whether and how Notch1 signaling modulates mechanical allodynia of CYP-induced cystitis. Methods. CYP was peritoneally injected to establish a bladder pain syndrome/interstitial cystitis (BPS/IC) rat model. A γ-secretase inhibitor, DAPT, was intrathecally injected to modulate Notch1 signaling indirectly. Mechanical withdrawal threshold in the lower abdomen was measured with von Frey filaments using the up-down method. The expression of Notch1 signaling, Iba-1, OX-42, TNF-α, and IL-1β in the L6-S1 spinal dorsal horn (SDH) was measured with Western blotting analysis and immunofluorescence staining. Results. Notch1 and Notch intracellular domain (NICD) were both upregulated in the SDH of the cystitis group. Moreover, the expression of Notch1 and NICD was negatively correlated with the mechanical withdrawal threshold of the cystitis rats. Furthermore, treatment with DAPT attenuated mechanical allodynia in CYP-induced cystitis and inhibited microglia activation, leading to decreased production of TNF-α and IL-1β. Conclusion. Notch1 signaling contributes to mechanical allodynia associated with CYP-induced cystitis by promoting microglia activation and neuroinflammation. Our study showed that inhibition of Notch1 signaling might have therapeutic value for treating pain symptoms in BPS/IC. [ABSTRACT FROM AUTHOR]

Interstitial cystitis/bladder pain syndrome (IC/BPS) seriously reduces the patient's quality of life, yet current therapies only provide partial relief. In the spinal dorsal horn (SDH), neuroinflammation plays a pivotal role in the development of IC. Injection of human umbilical cord mesenchymal stem cells (hUMSCs) to reduce inflammation is an effective strategy, and heme oxygenase-1 (HO-1) exhibits anti-nociceptive effect in neuroinflammatory pain. This study aimed to test the therapeutic effects of hUMSCs overexpressing HO-1 on cyclophosphamide-induced cystitis rat model. Cystitis rats were transplanted with altered cells and then assessed for 3 weeks. A series of behavioral measurements would be trial including suprapubic mechanical allodynia, depressive-like behaviors, micturition frequency, and short-term memory function. Additionally, western blot, immunofluorescence staining, and ELISA kit test for anti-inflammation effect. HUMSCs were capable of being transduced to overexpress HO-1. Injection of hUMSCs overexpressing HO-1 was more effective than hUMSCs alone in alleviating behavioral symptoms in rats. Furthermore, hUMSCs overexpressing HO-1 inhibited the activation of glial and TLR4/p65/NLRP3 pathway, decreased the levels of pro-inflammatory cytokines in the SDH region. Surprisingly, it markedly increased anti-inflammatory cytokine IL-10, reduced MDA content, and protected GSH concentrations in local environment. Our results suggest that injecting hUMSCs overexpressing HO-1 intrathecally can significantly promote functional outcomes in cystitis rats by reducing neuroinflammation, at least, partly through downregulating TLR4/p65/NLRP3 signaling pathway in the SDH region. This cell therapy affords a new strategy for IC/BPS treatment. [ABSTRACT FROM AUTHOR]

Background: Previous studies have demonstrated that glial cells play an important role in the generation and maintenance of neuropathic pain. Activated glial cells produce numerous mediators such as proinflammatory cytokines that facilitate neuronal activity and synaptic plasticity. Similarly, bladder pain syndrome/interstitial cystitis shares many characteristics of neuropathic pain. However, related report on the involvement of spinal glia in bladder pain syndrome/interstitial cystitis-associated pathological pain and the underlying mechanisms are still lacking. The present study investigated spinal glial activation and underlying molecular mechanisms in a rat model of bladder pain syndrome/interstitial cystitis. Results: A rat model of bladder pain syndrome/interstitial cystitis was established via systemic injection with cyclophosphamide. Mechanical allodynia was tested with von Frey monofilaments and up-down method. Moreover, Western blots and double immunofluorescence were used to detect the expression and location of glial fibrillary acidic protein, OX42/Iba1, P-P38, NeuN, interleukin (IL)-1β, phosphorylation of N-methyl-D-aspartate receptor 1 (P-NR1), and IL-1 receptor I (IL-1RI) in the L6-S1 spinal cord. We found that glial fibrillary acidic protein rather than OX42/Iba1 or P-P38 was significantly increased in the spinal cord of cyclophosphamide-induced cystitis. L-alpha-aminoadipate but not minocycline markedly attenuated the allodynia. Furthermore, we found that spinal IL-1β was dramatically increased in cyclophosphamide-induced cystitis, and activated astrocytes were the only source of IL-1β release, which contributed to allodynia in cystitis rats. Besides, spinal P-NR1 was statistically increased in cyclophosphamide-induced cystitis and only localized in IL-1RI positive neurons in spinal dorsal horn. Additionally, NR antagonist significantly attenuated the cystitis-induced pain. Interestingly, the time course of the P-NR1 expression paralleled to that of IL-1β or glial fibrillary acidic protein. Conclusions: Our results demonstrated that astrocytic activation but not microglial activation contributed to the allodynia in cyclophosphamide-induced cystitis and IL-1β released from astrocytes might bind to its endogenous receptor on the neurons inducing the phosphorylation of NR1 subunit, leading to sensory neuronal hyperexcitability and pathological pain. [ABSTRACT FROM AUTHOR]

Amphibious vehicles have the unique ability to maneuver on land and water, due to their distinctive structural characteristics, their hydrodynamic performance differs significantly from that of ships. With the growing demand for high-speed navigation of amphibious vehicles, research into resistance and methods to drag reduction has become a hot issue. In this paper, drag reduction technology for amphibious vehicles is reviewed based on a thorough analysis of existing research. Various amphibious vehicles from different countries are introduced, outlining their different movement states on the water and classified based on their drag reduction mechanisms. The article explores the working principle and effects of various drag reduction technology from two perspectives: universal technology and amphibious technology. Research indicates that applying fouling and biofouling effect, surface drag reduction, and air injection as universal technology can effectively reduce the sailing resistance of amphibious vehicles. Due to the limitations of universal technology in some special military amphibious vehicles, amphibious technology is discussed as a supplement, such as planing hull, retractable walking mechanism, and drag reduction accessories. Finally, a summary of drag reduction technology for amphibious vehicles is provided, including pertinent design recommendations and an introduction to potential research areas for future development. • Traditional amphibious vehicles are weak in speed, maneuverability, and drag reduction methods. • Turbulence improvement, air injection, hydrodynamic lift, and multi-hulled designs have been validated in the laboratory. • Universal drag reduction technologies can be promoted to amphibious vehicles. • Planing hull, retractable walking mechanism, drag reduction accessory are efficient amphibious drag reduction technologies. • Future works should focus on structural, manufacturing, shape optimization, materials, and control. [ABSTRACT FROM AUTHOR]

With the purpose to investigate the influence of joint dip angle and spacing on the TBM rock-breaking efficacy and cracking behaviour, experiments that include miniature cutter head tests are carried out on sandstone rock material. In the experiment, prefabricated joints of different forms are made in rock samples. Then theoretical analysis is conducted to improve the calculating models of the fractured work and crack length of rock in the TBM process. The experimental results indicate that lower rupture angles appear for specimens with joint dip angles between 45° and 60°. Meanwhile, rock-breaking efficacy for rock mass with joint dip angles in this interval is also higher. Besides, the fracture patterns are transformed from compressive shear mode to tensile shear mode as the joint spacing decreases. As a result, failure in a greater extent is resulted for specimens with smaller joint spacings. The results above suggest that joint dip angle between 45° and 60° and joint spacing of 1 cm are the optimal rock-breaking conditions for the tested specimens. Combining the present experimental data and taking the joint dip angle and spacing into consideration, the calculating model for rock fractured work that proposed by previous scholars is improved. Finally, theoretical solution of rock median and side crack length is also derived based on the analytical method of elastoplastic invasion fracture for indenter. The result of the analytical solution is also in good agreement with the actual measured experimental result. The present study may provide some primary knowledge about the rock cracking character and breaking efficacy under different engineering conditions. [ABSTRACT FROM AUTHOR]

Pine nut (Pinus koraiensis) meal protein peptides (PNMPP), a kind of Korean pine seed oil by-products, were often considered as waste disposal in food industry. In the present study, we found that 3–10 kDa PNMPP could enhance immunity of ICR mice at 100 mg·(kg·d)−1both in innate and in adaptive immunity. In innate immunity, PNMPP of 3–10 kDa at 100 mg·(kg·d)−1could enhance the abdominal macrophage phagocytosis of mice at 30.22% and the phagocytosis index of carbon clearance significantly (P < .05). In addition, we found out that 3–10 kDa PNMPP at low dose could significantly enhance cytokine interferon-γ, interleukin-2, interleukin-4, and interleukin-6 (P < .05). Meanwhile, in adaptive immunity, PNMPP could enhance the median hemolytic concentration of mice. These findings suggested that 100 mg·(kg·d)−1, 3–10 kDa PNMPP could increase the function of immunity. Abbreviations: ANOVA: analysis of variance; BSA: bull serum albumin; ConA: concanavalin A; CTX: cyclophosphamide; DW: deionized water; FCM: flow cytometry; IFN-γ: interferon-γ; IL-2: interleukin-2; IL-4: interleukin-4; IL-6: interleukin-6; MW: molecular weight; MPM: mouse peritoneal macrophages; OD: optical density; PBS: phosphate buffer solution; PNMPP: pine nut (Pinus koraiensis) meal protein peptides; SA: salicylic acid buffer; SRBC: sheep red blood cells; HC50: median hemolytic concentration [ABSTRACT FROM AUTHOR]

Background: Neuroinflammation in spinal dorsal horn (SDH) plays an important role in the pathogenesis of interstitial cystitis/bladder pain syndrome (IC/BPS). Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) exert potent anti-inflammatory activities in the treatment of various diseases. This study aimed to determine the therapeutic effects of MSC-EVs on IC and furtherly investigate the potential mechanism to attenuate neuroinflammation. Methods: Female IC rat model was established by intraperitoneal injection of cyclophosphamide (50 mg/kg, every 3 days for 3 doses). Inhibition of NLRP3 inflammasome was performed by intraperitoneal injection of MCC950 (10 mg/kg). MSC-EVs were isolated from the culture supernatants of human umbilical cord derived MSCs using ultracentrifugation, and then injected intrathecally into IC rats (20 μg in 10 μl PBS, every other day for 3 doses). Suprapubic mechanical allodynia was assessed using up-down method with von Frey filaments, and micturition frequency was examined by urodynamics. The expression of NLRP3 inflammasome components (NLRP3 and Caspase-1), glial cell markers (IBA-1 and GFAP), proinflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-18) and TLR4/NF-κB signal pathway (TLR4, p65 NK-κB and phospho-p65 NK-κB) in L6–S1 SDH was measured by Western blot analysis. The cellular localization of NLRP3 in SDH was detected using immunofluorescence co-staining. Results: NLRP3 inflammasome was activated in neurons in SDH of IC rats. NLRP3 inflammasome activation contributed to activation of glial cells and process of spinal neuroinflammation in IC rats, and was related to suprapubic mechanical allodynia and frequent micturition. Intrathecal injection of MSC-EVs alleviated suprapubic mechanical allodynia and frequent micturition in IC rats, restrained activation of glial cells and attenuated neuroinflammation in SDH. In addition, MSC-EV treatment significantly inhibited activation of both NLRP3 inflammasomes and TLR4/NF-κB signal pathway. Conclusions: NLRP3 inflammasome activation is involved in the neuroinflammation of IC. Intrathecal injection of MSC-EVs alleviates neuroinflammation and mechanical allodynia in IC by inhibiting the activation of NLRP3 inflammasome, and TLR4/NF-κB signal pathway may be the potential regulatory target. [ABSTRACT FROM AUTHOR]

BACKGROUND Egg-white protein polypeptides are potentially used as a functional ingredient in food products. In this study, the effects on DPPH inhibition of egg-white protein polypeptides ranging from 10 to 30 kDa treated by pulsed electric field ( PEF) technology were investigated. RESULTS 2, 2-Diphenyl-1-picrylhydrazyl ( DPPH) inhibition (%) was used to evaluate the antioxidant activity of polypeptides. In order to develop and optimize a pulsed electric field ( PEF) mathematical model for improving the antioxidant activity, we have investigated three variables, including concentration (6, 8 and 10 mg mL−1), electric field intensity (10, 20 and 30 kV cm−1) and pulse frequency (2000, 2350 and 2700 Hz) and subsequently optimized them by response surface methodology ( RSM). The concentration (8 mg mL−1), electric field intensity (10 kV cm−1) and pulse frequency (2000 Hz) were found to be the optimal conditions under which the DPPH inhibition increased 28.44%, compared to the sample without PEF treatment. Both near-infrared spectroscopy ( NIR) and mid-infrared spectroscopy ( MIR) were used to analyze the change of functional groups © 2012 Society of Chemical Industry. CONCLUSION The results showed that PEF technology could improve the antioxidant activity of antioxidant polypeptides from egg-white protein under the optimized conditions. [ABSTRACT FROM AUTHOR]

The long non-coding RNA (lncRNA) AGAP2-AS1 was implicated in tumorigenesis, yet with unclear mechanism in the development of Bladder Cancer (BCa). We collected the clinicopathological features and tissue samples of 45 patients with BCa in Xiangya Hospital. Expressions of AGAP2-AS1 and LRG1 were detected by RT-qPCR in BCa tissues and normal tissues as well as in BCa cells. The roles of AGAP2-AS1 and LRG1 were investigated by CCK-8, colony formation assay, transwell assays and tube formation assay. The subcellular localization of AGAP2-AS1 was detected by Fluorescence in situ hybridization. Bioinformatics method, RNA immunoprecipitation, RNA pull-down assay and Actinomycin D test were used to predict and identify the relationships between AGAP2-AS1, LRG1 and IGF2BP2. Xenografted tumors were produced to explore the function of AGAP2-AS1 in BCa in vivo. AGAP2-AS1 and LRG1 were highly upregulated in BCa. AGAP2-AS1 positively correlated with T stage, grade and vascular invasion, but negatively correlated with the survival of patients. Overexpressions of AGAP2-AS1 promoted proliferation, migration, invasion, tumor angiogenesis in vitro and tumor growth, metastasis in vivo, knockdown of AGAP2-AS1 exhibited the opposite effects. AGAP2-AS1 localized mainly in the cytoplasm. AGAP2-AS1 directly bound to IGF2BP2 protein to enhance LRG1 mRNA stability. Inhibition of BCa progression by AGAP2-AS1 knockdown may be reversed by LRG1 overexpression. AGAP2-AS1 can promote BCa progression and metastasis by recruiting IGF2BP2 to stabilize LRG1. LncRNA AGAP2-AS1 enhanced the stability of the LRG1 mRNA by recruiting the RNA-binding protein IGF2BP2 to the target gene LRG1 mRNA in the cytoplasm, so as to promot the proliferation, migration, invasion and angiogenesis of bladder cancer cells. [Display omitted] • We found AGAP2-AS1 was overexpressed in BCa, the high expression of AGAP2-AS1 was positively correlated with high pathological T stage, high grade and vascular invasion, but negatively correlated with the survival prognosis. High expression of AGAP2-AS1 and LRG1 promoted proliferation, migration, invasion of BCa cells and angiogenesis of tumor in vitro. AGAP2-AS1 also promoted tumor growth and metastasis in vivo. AGAP2-AS1 promoted the stability of LRG1 mRNA by recruiting the RNA binding protein IGF2BP2 to LRG1 mRNA. Morever, AGAP2-AS1 promoted uncontrolled proliferation, migration, invasion and angiogenesis of BCa cells in an LRG1-dependent manner, thereby accelerating the malignant progression of BCa. • According 45 BCa patients' tissues in our hospital, AGAP2-AS1 and LRG1 are upregulated in bladder cancer (BCa), pathological features such as pathological T stage, high grade, especially vascular infiltration were related to the level of AGAP2-AS1. • AGAP2-AS1 recruits IGF2BP2 to stabilize LRG1 mRNA in BCa, the co-localization of AGAP2-AS1, IGF2BP2 and LRG1 was confirmed by IF-FISH. • In addition to using bioinformatics methods to predict target genes, we employed a number of experimental methods to verify our conclusions. [ABSTRACT FROM AUTHOR]

The mechanism of interstitial cystitis/bladder pain syndrome (IC/BPS) remains unclear to date, but reports showed that bladder inflammation and increasing number of activating mast cells in bladder tissues were common in patients with IC/BPS. Houttuynia cordata is widely used in Chinese traditional medicine, and its function of anti-inflammation has been proved. The purpose of this study was to investigate the efficacy and possible mechanisms of the Houttuynia cordata (HC) extract in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS). In the current study, a total of 30 adult female rats were randomly divided into three groups: sham group (n = 10), cyclophosphamide + saline (CYP + NS) group (n = 10), and cyclophosphamide + Houttuynia cordata extract (CYP + HC) group (n = 10). The animal model of IC/BPS was induced with cyclophosphamide (75 mg/kg, intraperitoneal injection, once every 3 days for 10 days) in the CYP + NS group and CYP + HC group, and sham rats received a volume-matched injection of saline. After anesthesia with urethane (0.8 g/kg, intraperitoneal injection), intravesical administration of either saline (1 ml) or Houttuynia cordata extract (1 ml, 2 g/ml) was continued once per day for a week in the CYP + NS group and CYP + HC group, respectively. Subsequently, urinary frequency, nociceptive behaviors, cystometry, bladder weight, histological changes, and cytokine (IL-6, IL-8, TNF-α) concentration were evaluated and compared among the three groups. Variables including inflammatory grade, mast cell number, proportion of activated mast cells, bladder weight, cytokine concentration of bladder homogenates, and frequency of urination significantly increased in the CYP + NS group compared with the sham group (P < 0.01) and CYP + HC group (P < 0.01). Besides, compared with the CYP + NS group, longer intercontraction interval, bigger bladder capacity, higher nociceptive threshold, fewer number of mast cells, and lower proportion of activated mast cells were found in the CYP + HC group (P < 0.01). Our study demonstrated that the Houttuynia cordata extract can effectively inhibit mast cell proliferation and activation and downregulate proinflammatory cytokine in a rat model of IC/BPS induced with cyclophosphamide and might be potentially valuable for the treatment of IC/BPS. [ABSTRACT FROM AUTHOR]

Background: Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) often grieve over a low quality of life brought about by chronic pain. In our previous studies, we determined that neuroinflammation of the spinal dorsal horn (SDH) was associated with mechanisms of interstitial cystitis. Moreover, it has been shown that brain-derived neurotrophic factor (BDNF) participates in the regulation of neuroinflammation and pathological pain through BDNF-TrkB signaling; however, whether it plays a role in cyclophosphamide (CYP)-induced cystitis remains unclear. This study aimed to confirm whether BDNF-TrkB signaling modulates neuroinflammation and mechanical allodynia in CYP-induced cystitis and determine how it occurs.Methods: Systemic intraperitoneal injection of CYP was performed to establish a rat cystitis model. BDNF-TrkB signaling was modulated by intraperitoneal injection of the TrkB receptor antagonist, ANA-12, or intrathecal injection of exogenous BDNF. Mechanical allodynia in the suprapubic region was assessed using the von Frey filaments test. The expression of BDNF, TrkB, p-TrkB, Iba1, GFAP, p-p38, p-JNK, IL-1β, and TNF-α in the L6-S1 SDH was measured by Western blotting and immunofluorescence analysis.Results: BDNF-TrkB signaling was upregulated significantly in the SDH after CYP was injected. Similarly, the expressions of Iba1, GFAP, p-p38, p-JNK, IL-1β, and TNF-α in the SDH were all upregulated. Treatment with ANA-12 could attenuate mechanical allodynia, restrain activation of astrocytes and microglia and alleviate neuroinflammation. Besides, the intrathecal injection of exogenous BDNF further decreased the mechanical withdrawal threshold, promoted activation of astrocytes and microglia, and increased the release of TNF-α and IL-1β in the SDH of our CYP-induced cystitis model.Conclusions: In our CYP-induced cystitis model, BDNF promoted the activation of astrocytes and microglia to release TNF-α and IL-1β, aggravating neuroinflammation and leading to mechanical allodynia through BDNF-TrkB-p38/JNK signaling. [ABSTRACT FROM AUTHOR]

The physical and mechanical properties of rocks at high temperatures change considerably with geothermal exploitation, underground coal gasification, and nuclear engineering construction, posing a threat to the safety of underground engineering. To investigate the effect of temperature on micro‐ and macroscale damage of sandstone, a series of uniaxial compressive strength (UCS) tests were conducted using an MTS 815 mechanical testing system. Acoustic emission (AE) monitoring, scanning electron microscopy (SEM), and nuclear magnetic resonance (NMR) were also employed. Macroscopically, it was found that the physical and mechanical properties of sandstone change with treatment temperature, but these changes do not follow a monotonic trend. In addition, the brittle‐ductile transition occurs at approximately 600°C, which is further confirmed by AE monitoring. Regarding the microstructural evolution of sandstone, the percentage of micropores shows a monotonically decreasing trend with increasing treatment temperature. The change in mesopores decreases slightly first, then shows a gradual increase, and finally decreases. The macropores first decrease and subsequently increase with increasing temperature. The decreasing trend of the meso‐ and macropores is attributed to thermal expansion at a relatively low temperature. However, the decrease in mesopores is due to their coalescence into macropores at higher temperatures. Furthermore, the integral value of the NMR spectrum first decreases and then increases with increasing treatment temperature, corresponding to the decrease in porosity from 25°C to 200°C, and then increases with temperature to 900°C. Finally, a constitutive model for the deformation and fracture of sandstone is established based on the effective medium theory and AE energy. The present study is helpful for improving the understanding of the process of thermal damage sandstone from both micro‐ and macroscale perspectives. [ABSTRACT FROM AUTHOR]

Neuroinflammation in the spinal dorsal horn (SDH) region plays an important role in the pathogenesis of interstitial cystitis (IC)/bladder pain syndrome (BPS). Oxidative stress is an important etiological factor for inflammatory diseases. This study aimed to investigate the therapeutic effects of umbilical cord mesenchymal stem cells UMSCs on neuroinflammation and oxidative stress in IC and the underlying mechanisms. Rats were intraperitoneally injected with cyclophosphamide (50 mg/kg bodyweight) to establish the IC animal model. Additionally, rats were intrathecally injected with a Sirt1-specific agonist (SRT1720; 8 μg/rat) or inhibitor (EX527; 8 μg/rat). Furthermore, rats were intrathecally injected with human UMSCs (hUMSCS; 8 × 105 cells/rat). Rat behavior was examined using the mechanical allodynia test, novel object recognition test, sucrose preference test, and urodynamics analysis. Neuroinflammation and oxidative stress the SDH region were examined using western blotting, immunofluorescence, enzyme-linked immunosorbent assay, and commercial kits. The Sirt1/Nrf2/HO-1 pathway was downregulated in IC rats. Sirt1 activation and inhibition differentially affected the behavior of IC rats. hUMSCs effectively mitigated the upregulation of oxidative stress, proinflammatory cytokines, and glial activation in the SDH region. Additionally, hUMSCs suppressed mechanical allodynia, dysregulated urodynamics, memory deficits, and depressive-like behavior in IC rats. hUMSCs exerted therapeutic effects through the Sirt1/Nrf2/HO-1 pathway. intrathecal hUMSCs injection alleviated behavioral deficits of IC rats by mitigating neuroinflammation and oxidative stress through the Sirt1/Nrf2/HO-1 pathway and can be potentially an effective therapeutic strategy for IC. • Oxidative stress is involved in neuroinflammation of cystitis rat. • Sirt1 widely expressed in the nucleus of the spinal dorsal horn region in cystitis rat • Intrathecally injected umbilical cord mesenchymal stem cells for anti-neuroinflammation and oxidative stress in cystitis rat • Umbilical cord mesenchymal stem cells improving outcome of cystitis rat by upregulating Sirt1/Nrf2/HO-1 pathway [ABSTRACT FROM AUTHOR]

• The stress state of compressive-shear is considered. • An extended non-ordinary state-based peridynamiscs theory is implemented. • The fracture characteristic of flawed rock-like materials is studied. • The fracture failure mechanism of flawed rock-like materials is revealed. An extended non-ordinary state-based peridynamic (NOSB-PD) theory is utilized to investigate the fracture characteristics of rock-like materials containing intermittent flaws under compressive-shear loading. The stress-based failure criteria, i.e., the maximum tensile stress criterion and the Mohr-Coulomb criterion, are integrated into the NOSB-PD theory to respectively determine the tensile failure and shear failure of flawed rock-like materials. The distribution characteristics of maximum principal stress and shear stress acquired by the NOSB-PD theory are employed to analyze the fracture failure mechanism of flawed rock-like materials under compressive-shear loading. The effects of inclination angle of the central flaw on the initiation and coalescence modes of flawed rock-like specimens are investigated. The numerical results of flawed rock-like materials are in good agreement with the experimental results. The extended NOSB-PD has the ability to simulate the fracture processes under compressive-shear loading. [ABSTRACT FROM AUTHOR]

• The nonlinear energy self-promotion-inhibition model were proposed. • The law of nonlinear energy evolution were proposed. • The crack closure and propagation nonlinear behavior under UCS test were discovered. • Threshold stress indicators for micro cracks' closure and propagation were proposed. The development of dissolution underground results in the appearance of holes of different shapes in limestone, which affect its deformation and failure characteristics. Generally, the deformation and failure of the rock mass are accompanied by energy dissipation and release. To investigate the nonlinear energy evolution mechanism, a series of uniaxial compression and acoustic emission (AE) tests were conducted on limestone with holes of different shapes. Subsequently, based on the theory of nonlinear dynamics and rock micro-energy evolution, a nonlinear energy self-promotion-inhibition model and a nonlinear energy evolution law for limestone were proposed. The nonlinear energy self-promotion- inhibition model suggested an energy mechanism that could inhabit energy development, particularly when a critical failure occurred. In addition, the crack closure and propagation nonlinear behavior characteristics were investigated via a UCS test. Experimental results showed that energy promotion and inhibition occurred during loading, where the effect of the former was greater than that of the latter. Additionally, the energy promotion and inhibition effects of limestone with a "mushroom-shaped hole" were more significant than those of intact and other limestones. The "base" of limestone with a "dumbbell-shaped hole" reduced the stress concentration of the samples. Based on the nonlinear characteristics of the average growth rate of elastic strain energy density and the stress-time curve, the evolution of limestone with holes of different shapes under uniaxial compression can be categorized into five main stages, which can be further classified into seven substages based on the AE characteristics. Moreover, three threshold stress indicators, i.e., initial equilibrium stress, periodic crack growth stress, and chaotic initial stress, for describing the closure and propagation of microcracks were proposed. The results of this study reveal the nonlinear energy evolution mechanism of limestone with holes of different shapes and provide a basis for further research on the meso -evolution of rock mass. [ABSTRACT FROM AUTHOR]

Abstract: Antioxidant polypeptides of molecular weight (MW) ranging from 10 to 30kDa were produced from egg-white protein powder by enzyme hydrolysis and ultrafiltration (UF). Ferric reducing antioxidant potential (FRAP) value (mmol Fe2+/g) was used to evaluate the antioxidant activity. One-factor-at-a-time (OFAT) tests and Box–Behnken design (BBD) of response surface methodology (RSM) were used to investigate the effect of pulsed electric field (PEF) treatment parameters on antioxidant activity of polypeptides. The optimal conditions were as follows: concentration 8mg/mL, electric field intensity 10kV/cm, and pulse frequency 2000Hz, under which, the FRAP value increased 44.23%, compared to the antioxidant activity of the polypeptides without PEF treatment. Both near-infrared spectroscopy (NIR) and mid-infrared spectroscopy (MIR) were used to analyze the change of functional groups. [Copyright &y& Elsevier]

Objective: To investigate the relationship between surgeon's experience, tumor characteristics, absent detrusor muscle (DM) tissue in resected specimens, and residual tumor after an initial transurethral resection. Patients and Methods: We conducted an analysis of 216 patients from two centers over a 3-year period. Patients with primary bladder tumors that were judged to have been completely resected were recruited. The data included tumor characteristics, surgeon category, and DM status. Logistic regression multivariate analyses were conducted. Results: Large tumors, lateral/dome/anterior wall tumors, and surgery performed by junior surgeons were independently associated with absent DM. Large tumors, dome/anterior wall tumors, T1 and absent DM were independently associated with residual disease. The absence and presence of the DM were associated with residual tumor rates of 51.8 and 20.9%, respectively (OR 15.537). Resection by senior surgeons was associated with the presence of DM and clean resection (OR 0.274 and 0.141, respectively). Conclusions: Absent DM and residual tumor were more likely to occur in cases involving large tumors that were located in the lateral/dome/anterior wall, especially when the surgery was performed by a junior surgeon. Absent DM appears to be a surrogate marker for residual disease. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]