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Abstract Purpose To analyze the role of and mechanism underlying obstructive sleep apnea (OSA)-derived exosomes in inducing non-alcoholic fatty liver (NAFLD). Methods The role of OSA-derived exosomes was analyzed in inducing hepatocyte fat accumulation in mice models both in vivo and in vitro. Results OSA-derived exosomes caused fat accumulation and macrophage activation in the liver tissue. These exosomes promoted fat accumulation; steatosis was more noticeable in the presence of macrophages. Macrophages could internalize OSA-derived exosomes, which promoted macrophage polarization to the M1 type. Moreover, it inhibited sirtuin-3 (SIRT3)/AMP-activated protein kinase (AMPK) and autophagy and promoted the activation of nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) inflammasomes. The use of 3-methyladenine (3-MA) to inhibit autophagy blocked NLRP3 inflammasome activation and inhibited the M1 polarization of macrophages. miR-421 targeting inhibited SIRT3 protein expression in the macrophages. miR-421 was significantly increased in OSA-derived exosomes. Additionally, miR-421 levels were increased in OSA + NAFLD mice- and patient-derived exosomes. In the liver tissues of OSA and OSA + NAFLD mice, miR-421 displayed similar co-localization with the macrophages. Intermittent hypoxia-induced hepatocytes deliver miR-421 to the macrophages via exosomes to inhibit SIRT3, thereby participating in macrophage M1 polarization. After OSA and NAFLD modeling in miR-421−/− mice, liver steatosis and M1 polarization were significantly reduced. Additionally, in the case of miR-421 knockout, the inhibitory effects of OSA-derived exosomes on SIRT3 and autophagy were significantly alleviated. Furthermore, their effects on liver steatosis and macrophage M1 polarization were significantly reduced. Conclusions OSA promotes the delivery of miR-421 from the hepatocytes to macrophages. Additionally, it promotes M1 polarization by regulating the SIRT3/AMPK-autophagy pathway, thereby causing NAFLD.

Abstract A correlation exists between obstructive sleep apnoea (OSA) and the severity of metabolic dysfunction-associated steatotic liver disease (MASLD), OSA can induce more severe MASLD. However, the underlying regulatory mechanism between the two is unclear. To this end, this study explored the role and possible molecular mechanisms of adipocyte-derived exosomes under OSA in aggravating MASLD. Through sequencing technology, miR-455-3p was identified as a co-differentially expressed miRNA between the MASLD + OSA and Control groups and between the MASLD + OSA and MASLD groups. Upregulation of TCONS-00039830 and Smad2 and downregulation of miR-455-3p in the MASLD and MASLD + OSA groups were validated in vivo and in vitro. TCONS-00039830, as a differentially expressed LncRNA in exosomes found in the sequencing results, transfection notably downregulated miR-455-3p and upregulated Smad2 in hepatocytes. TCONS_00039830 overexpression increased fat, triglyceride and cholesterol levels, while miR-455-3p overexpression decreased these levels. Furthermore, exosome administration promoted the accumulation of fat, triglyceride and cholesterol, upregulated TCONS_00039830 and Smad2, and downregulated miR-455-3p. Overexpression of miR-455-3p reversed the increased fat accumulation and upregulated TCONS_00039830 and Smad2. In conclusion, OSA-derived exosomes promoted hepatocyte steatosis by regulating TCONS_00039830/miR-455-3p/Smad2 axis, thereby aggravating liver damage in MASLD.

BackgroundThe escalation of global population aging has accentuated the prominence of senile diabetes mellitus (SDM) as a consequential public health concern. Oxidative stress and chronic inflammatory cascades prevalent in individuals with senile diabetes significantly amplify disease progression and complication rates. Traditional Chinese Medicine (TCM) emerges as a pivotal player in enhancing blood sugar homeostasis and retarding complication onset in the clinical management of senile diabetes. Nonetheless, an evident research gap persists regarding the integration of TCM’s renal tonification pharmacological mechanisms with experimental validation within the realm of senile diabetes therapeutics.AimsThe objective of this study was to investigate the mechanisms of action of New Shenqi Pills (SQP) in the treatment of SDM and make an experimental assessment.MethodsNetwork analysis is used to evaluate target pathways related to SQP and SDM. Mitochondrial-related genes were obtained from the MitoCarta3.0 database and intersected with the common target genes of the disease and drugs, then constructing a protein-protein interaction (PPI) network making use of the GeneMANIA database. Representative compounds in the SQP were quantitatively measured using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to ensure quality control and quantitative analysis of the compounds. A type 2 diabetes mice (C57BL/6) model was used to investigate the pharmacodynamics of SQP. The glucose lowering efficacy of SQP was assessed through various metrics including body weight and fasting blood glucose (FBG). To elucidate the modulatory effects of SQP on pancreatic beta cell function, we measured oral glucose tolerance test (OGTT), insulin histochemical staining and tunel apoptosis detection, then assessed the insulin-mediated phosphoinositide 3-kinase (PI3K)/protein kinase A (Akt)/glycogen synthase kinase-3β (GSK-3β) pathway in diabetic mice via Western blotting. Additionally, we observe the structural changes of the nucleus, cytoplasmic granules and mitochondria of pancreatic islet β cells.ResultsIn this investigation, we identified a total of 1876 genes associated with senile diabetes, 278 targets of SQP, and 166 overlapping target genes, primarily enriched in pathways pertinent to oxidative stress response, peptide response, and oxygen level modulation. Moreover, an intersection analysis involving 1,136 human mitochondrial genes and comorbidity targets yielded 15 mitochondria-related therapeutic targets. Quality control assessments and quantitative analyses of SQP revealed the predominant presence of five compounds with elevated concentrations: Catalpol, Cinnamon Aldehyde, Rehmanthin D, Trigonelline, and Paeonol Phenol. Vivo experiments demonstrated notable findings. Relative to the control group, mice in the model group exhibited significant increases in body weight and fasting blood glucose levels, alongside decreased insulin secretion and heightened islet cell apoptosis. Moreover, β-cells nuclear condensation and mitochondrial cristae disappearance were observed, accompanied by reduced expression levels of p-GSK-3β protein in islet cells (p < 0.05 or p < 0.01). Conversely, treatment groups administered SQP and Rg displayed augmented expressions of the aforementioned protein markers (p < 0.05 or p < 0.01), alongside preserved mitochondrial cristae structure in islet β cells.ConclusionOur findings suggest that SQP can ameliorate diabetes by reducing islet cell apoptosis and resist oxidative stress. These insulin-mediated PI3K/AKT/GSK-3β pathway plays an important regulatory role in this process.

This review provides a comprehensive analysis of the critical role played by macrophages and their underlying mechanisms in the progression of diabetic cardiomyopathy (DCM). It begins by discussing the origins and diverse subtypes of macrophages, elucidating their spatial distribution and modes of intercellular communication, thereby emphasizing their significance in the pathogenesis of DCM. The review then delves into the intricate relationship between macrophages and the onset of DCM, particularly focusing on the epigenetic regulatory mechanisms employed by macrophages in the context of DCM condition. Additionally, the review discusses various therapeutic strategies aimed at targeting macrophages to manage DCM. It specifically highlights the potential of natural food components in alleviating diabetic microvascular complications and examines the modulatory effects of existing hypoglycemic drugs on macrophage activity. These findings, summarized in this review, not only provide fresh insights into the role of macrophages in diabetic microvascular complications but also offer valuable guidance for future therapeutic research and interventions in this field.

BackgroundDespite advancements, breast cancer outcomes remain stagnant, highlighting the need for precise biomarkers in precision medicine. Traditional TNM staging is insufficient for identifying patients who will respond well to treatment.MethodsOur study involved over 6,900 breast cancer patients from 14 datasets, including in-house clinical data and single-cell data from 8 patients (37,451 cells). We integrated 10 machine learning algorithms in 55 combinations and analyzed 100 existing breast cancer signatures. IHC assays were conducted for validation, and potential immunotherapies and chemotherapies were explored.ResultsWe pinpointed six stable Panoptosis-related genes from multi-center cohorts, leading to a robust Panoptosis-model. This model outperformed existing clinical and molecular features in predicting recurrence and mortality risks, with high-risk patients showing worse outcomes. IHC validation from 30 patients confirmed our findings, indicating the model’s broader applicability. Additionally, the model suggested that low-risk patients benefit more from immunotherapy, while high-risk patients are sensitive to specific chemotherapies like BI-2536 and ispinesib.ConclusionThe Panoptosis-model represents a major advancement in breast cancer prognosis and treatment personalization, offering significant insights for effectively managing a wide range of breast cancer patients.

DNA repair is a vital mechanism in cells that protects against DNA damage caused by internal and external factors. It involves a network of signaling pathways that monitor and transmit damage signals, activating various cellular activities to repair DNA damage and maintain genomic integrity. Dysfunctions in this repair pathway are strongly associated with the development and progression of cancer. However, they also present an opportunity for targeted therapy in breast cancer. Extensive research has focused on developing inhibitors that play a crucial role in the signaling pathway of DNA repair, particularly due to the remarkable success of PARP1 inhibitors (PARPis) in treating breast cancer patients with BRCA1/2 mutations. In this review, we summarize the current research progress and clinical implementation of BRCA and BRCAness in targeted treatments for the DNA repair pathway. Additionally, we present advancements in diverse inhibitors of DNA repair, both as individual and combined approaches, for treating breast cancer. We also discuss the clinical application of DNA repair-targeted therapy for breast cancer, including the rationale, indications, and summarized clinical data for patients with different breast cancer subtypes. We assess their influence on cancer progression, survival rates, and major adverse reactions. Last, we anticipate forthcoming advancements in targeted therapy for cancer treatment and emphasize prospective areas of development.

Diabetic cardiomyopathy is a chronic cardiovascular complication caused by diabetes that is characterized by changes in myocardial structure and function, ultimately leading to heart failure and even death. Mitochondria serve as the provider of energy to cardiomyocytes, and mitochondrial dysfunction plays a central role in the development of diabetic cardiomyopathy. In response to a series of pathological changes caused by mitochondrial dysfunction, the mitochondrial quality control system is activated. The mitochondrial quality control system (including mitochondrial biogenesis, fusion and fission, and mitophagy) is core to maintaining the normal structure of mitochondria and performing their normal physiological functions. However, mitochondrial quality control is abnormal in diabetic cardiomyopathy, resulting in insufficient mitochondrial fusion and excessive fission within the cardiomyocyte, and fragmented mitochondria are not phagocytosed in a timely manner, accumulating within the cardiomyocyte resulting in cardiomyocyte injury. Currently, there is no specific therapy or prevention for diabetic cardiomyopathy, and glycemic control remains the mainstay. In this review, we first elucidate the pathogenesis of diabetic cardiomyopathy and explore the link between pathological mitochondrial quality control and the development of diabetic cardiomyopathy. Then, we summarize how clinically used hypoglycemic agents (including sodium-glucose cotransport protein 2 inhibitions, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, thiazolidinediones, metformin, and α-glucosidase inhibitors) exert cardioprotective effects to treat and prevent diabetic cardiomyopathy by targeting the mitochondrial quality control system. In addition, the mechanisms of complementary alternative therapies, such as active ingredients of traditional Chinese medicine, exercise, and lifestyle, targeting mitochondrial quality control for the treatment of diabetic cardiomyopathy are also added, which lays the foundation for the excavation of new diabetic cardioprotective drugs.

Abstract Achieving satisfactory performance for a solid‐state Na‐metal battery (SSNMB) with an inorganic solid electrolyte (SE), especially under freezing temperatures, poses a challenge for stabilizing a Na‐metal anode. Herein, this challenge is addressed by utilizing a Natrium super ionic conductor (NASICON) NASICON‐type solid electrolyte, enabling the operation of a rechargeable SSNMB over a wide temperature range from −20 to 45 °C. The interfacial resistance at the Na metal/SE interface is only 0.4 Ω cm2 at 45 °C and remains below 110 Ω cm2 even at −20 °C. Remarkably, long‐term Na‐metal plating/stripping cycles lasting over 2000 h at −20 °C are achieved with minimal polarization voltages at 0.1 mA cm−2. Further analysis reveals the formation of a uniform Na3−xCaxPO4 interphase layer at the interface, which significantly contributes to the exceptional interfacial performance observed. By employing a Na3V1.5Al0.5(PO4)3 cathode, the full battery system demonstrates excellent adaptability to low temperatures, exhibiting a capacity of 80 mA h g−1 at −20 °C over 50 cycles and retaining a capacity of 108 mAh g−1 (88.5% of the capacity at 45 °C) at 0 °C over 275 cycles. This research significantly reduces the temperature threshold for SSNMB operation and paves the way toward solid‐state batteries suitable for all‐season applications.

Defects on fabric surfaces are difficult to identify owing to unsuitable computing devices, highly complex algorithms, small size, and high degree of integration with the fabric. To this end, this study proposes a lightweight fabric defect-detection network, YOLO-SCD, based on attention mechanism. The introduction of depth-wise separable convolution and the attention mechanism enhanced the capacity of the neck network to extract the defective features and increased the detection speed of the overall network. The extensive experimental results revealed that YOLO-SCD achieved an average accuracy of 82.92%, effective improvement of 8.49% in mAP, and an improvement of 37 fps compared to the original YOLOv4 on a standard fabric defect dataset. By leveraging its swift detection speed and high efficiency, YOLO-SCD excels in both the general fabric defect category and the difficult-to-detect fabric. Overall, it exhibited strong performance in detecting both minor flaws and flaws with high fabric integration. Furthermore, the proposed model was extended to steel datasets with similar characteristics.

Abstract The structural parameters of multibell underreamed anchors play a crucial role in anchoring performance. The parameters of multibell underreamed anchor investigations are helpful when exploring optimized anchor structures. Based on the results of small-scale physical modelling tests, two types of multibell underreamed anchors were adopted under vertical uplifting loads. Numerical investigations were employed to study the effect of bell spacing, underream structure and bell dimension on the ultimate uplift bearing capacity. After an analysis of the anchorage mechanism, the anchoring efficiency was evaluated by the anchoring force provided by the unit concrete usage of the anchor, and the structural parameter λ equal to the surface area ratios of the expanded bell cone to the straight shaft between bells was defined. Then, the anchoring efficiency optimized structural parameters were presented. An analysis of model tests and simulation results showed that compared to concave bell surfaces, the convex shape could enhance the ultimate bearing capacity of a multibell underreamed anchor. There is an optimal value for the spacing of neighbouring bells, and there are three models of mechanisms for multibell anchors pulling out. When λ ∈ [1, 1.8], the multibell anchors can perform most efficiently to achieve their structural advantages.

Cognitive dysfunction is increasingly recognized as a complication and comorbidity of diabetes, supported by evidence of abnormal brain structure and function. Although few mechanistic metabolic studies have shown clear pathophysiological links between diabetes and cognitive dysfunction, there are several plausible ways in which this connection may occur. Since, brain functions require a constant supply of glucose as an energy source, the brain may be more susceptible to abnormalities in glucose metabolism. Glucose metabolic abnormalities under diabetic conditions may play an important role in cognitive dysfunction by affecting glucose transport and reducing glucose metabolism. These changes, along with oxidative stress, inflammation, mitochondrial dysfunction, and other factors, can affect synaptic transmission, neural plasticity, and ultimately lead to impaired neuronal and cognitive function. Insulin signal triggers intracellular signal transduction that regulates glucose transport and metabolism. Insulin resistance, one hallmark of diabetes, has also been linked with impaired cerebral glucose metabolism in the brain. In this review, we conclude that glucose metabolic abnormalities play a critical role in the pathophysiological alterations underlying diabetic cognitive dysfunction (DCD), which is associated with multiple pathogenic factors such as oxidative stress, mitochondrial dysfunction, inflammation, and others. Brain insulin resistance is highly emphasized and characterized as an important pathogenic mechanism in the DCD.

Colorectal cancer (CRC) is a major health burden, accounting for approximately 10% of all new cancer cases worldwide. Accumulating evidence suggests that the crosstalk between the host mucins and gut microbiota is associated with the occurrence and development of CRC. Mucins secreted by goblet cells not only protect the intestinal epithelium from microorganisms and invading pathogens but also provide a habitat for commensal bacteria. Conversely, gut dysbiosis results in the dysfunction of mucins, allowing other commensals and their metabolites to pass through the intestinal epithelium, potentially triggering host responses and the subsequent progression of CRC. In this review, we summarize how gut microbiota and bacterial metabolites regulate the function and expression of mucin in CRC and novel treatment strategies for CRC.

The pathophysiological mechanisms of diabetic cardiomyopathy have been extensively studied, but there is still a lack of effective prevention and treatment methods. The ability of flavonoids to protect the heart from diabetic cardiomyopathy has been extensively described. In recent years, epigenetics has received increasing attention from scholars in exploring the etiology and treatment of diabetes and its complications. DNA methylation, histone modifications and non-coding RNAs play key functions in the development, maintenance and progression of diabetic cardiomyopathy. Hence, prevention or reversal of the epigenetic alterations that have occurred during the development of diabetic cardiomyopathy may alleviate the personal and social burden of the disease. Flavonoids can be used as natural epigenetic modulators in alternative therapies for diabetic cardiomyopathy. In this review, we discuss the epigenetic effects of different flavonoid subtypes in diabetic cardiomyopathy and summarize the evidence from preclinical and clinical studies that already exist. However, limited research is available on the potential beneficial effects of flavonoids on the epigenetics of diabetic cardiomyopathy. In the future, clinical trials in which different flavonoids exert their antidiabetic and cardioprotective effects through various epigenetic mechanisms should be further explored.

Introduction. Serine hydroxymethyltransferase 2 (SHMT2) has a critical role in serine-glycine metabolism to drive cancer cell proliferation. Yet, the function of SHMT2 in tumorigenesis, especially in human colorectal cancer (CRC) progression, remains largely unclear. Materials and Methods. CRC and paired normal samples were collected in the Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, and assessed by real-time polymerase chain reaction (qPCR) analysis, western blot (WB), and immunohistochemistry (IHC). Moreover, SHMT2 expression in human CRC cells was identified by qPCR and WB. The CRC cell proliferation, migration, and invasion after SHMT2 knockdown were explored through in vitro and in vivo assays. mRNA-seq assays were used to investigate the underlying mechanisms behind the SHMT2 function. Results. It was found that SHMT2 mRNA and protein were overexpressed in CRC tissue compared to the levels in normal mucosa. Positive expression of SHMT2 was significantly correlated with TNM stage and lymph node metastasis, and elevated expression of SHMT2 resulted as an independent prognostic factor in patients with CRC. SHMT2 knockdown impaired the proliferation of CRC in vitro and in vivo and induced cell cycle arrest by regulating UHRF1 expression. Conclusion. Taken together, our findings reveal that UHRF1 is a novel target gene of SHMT2, which can be used as a potential therapeutic strategy for CRC therapy.

High-speed railway tunnels in various countries have continuously reported accidents of vault falling concrete blocks. Once the concrete block falling occurs, serious consequences follow, and traffic safety may be endangered. The aerodynamic shockwave evolves from the initial compression wave may be an important inducement causing the tunnel lining cracks to grow and form falling concrete blocks. A joint calculation framework is established based on ANSYS Fluent, ABAQUS, and FRANC3D for calculating the crack tip field under the aerodynamic shockwave. The intensification effect of aerodynamic shockwaves in the crack is revealed, and the evolution characteristics of the crack tip field and the influence factors of stress intensity factor (SIF) are analyzed. Results show that (1) the aerodynamic shockwave intensifies after entering the crack, resulting in more significant pressure in the crack than the input pressure. The maximum pressure of the inclined and longitudinal cracks is higher than the corresponding values of the circumferential crack, respectively. (2) The maximum SIF of the circumferential, inclined, and longitudinal crack appears at 0.5, 0.68, and 0.78 times the crack front length. The maximum SIF of the circumferential crack is higher than that of the inclined and longitudinal crack. The possibility of crack growth of the circumferential crack is the highest under aerodynamic shockwaves. (3) The influence of train speed on the SIF of the circumferential crack is more than 40%. When the train speed, crack depth, and crack length change, the change of pressure in the crack is the direct cause of the change of SIF. [ABSTRACT FROM AUTHOR]

To reduce the damage caused by geological disasters to human beings, accurate monitoring of geological information in natural environment is of great significance. Based on the correlation between geological hazards and remote sensing technology, the study introduces the faster regions with convolutional neural network (Faster R-CNN) algorithm, further utilizes feature extraction network, modifies the training method and optimizes the algorithm, so that it can be applied to remote sensing technology to improve the speed and accuracy of geological hazards detection. Finally, the PASCAL VOC and COCO datasets are used for the experimental evaluation and demonstration of the proposed method model. The results show that when the GIOU value is 0.6, the detection accuracy reaches the best. In the algorithm comparison, the AP@0.5 value of the improved Faster R-CNN algorithm designed in the study reaches 59, proving that the algorithm is satisfactory in both speed and accuracy, and achieves the expected goal of target detection. Moreover, the Faster R-CNN algorithm can be effectively applied to satellite remote sensing technology to quickly detect geological information in natural environment and make early warning measures by judging its attribute transformation, thus reducing losses caused by geological changes. [ABSTRACT FROM AUTHOR]

Physics-informed neural networks (PINNs) have recently emerged and attracted extensive attention as an alternative approach to computational fluid dynamics (CFD) methods, which can provide competitive solutions to a variety of forward and inverse fluid problems. In this study, we reconstruct a 3D wind field around a building model in wind tunnel test with a Reynolds number of 2.4 × 104 by formulating a novel PINN framework, which is the first exploration of PINNs for building wind engineering problems. To surmount the hurdle in multi-objective optimization for PINN training, a dynamic prioritization (dp) self-adaptive loss balance strategy is proposed (termed dpPINN), which adaptively reconciles the loss terms of distinct scales to facilitate convergence in PINN training. A zero-equation turbulence model and the wind velocity data collected in near-wall regions are embedded in dpPINN training. Comparison results indicate that dpPINN predictions show good consistency with observation data, which is superior to two current PINN paradigms in prediction accuracy. Furthermore, the influence of neural network configurations, turbulence models, and the layout arrangements of training points on the dpPINN prediction is investigated. It is demonstrated that the dpPINN could be a powerful auxiliary means for airflow simulation and reconstruction in wind engineering applications. [ABSTRACT FROM AUTHOR]

The high-speed railway has become an important passenger transport mode. Relying on the abundant passenger transport experience and expansive railway network, the high-speed freight train (HSFT) is feasible to be developed and has great application potential. As a critical component of HSFT, the cargo plays an important role in the overturning safety of HSFT under strong wind conditions. Previous studies about the aerodynamic performance of the high-speed train usually regarded the loaded carbody as an individual rigid body. Limited attention was paid to the variability inside the vehicle. In order to improve the running safety of HSFT under strong wind conditions, the multibody dynamics simulation is adopted to demonstrate the effect of cargo property on the overturning risk of HSFT under the aerodynamic loads obtained through the computational fluid dynamics (CFD) simulations. It is demonstrated that the inner side crosswind is more dangerous than the outer side crosswind. The speed of HSFT should be limited according to the cargo quantity, and the maximum speed for a fully loaded HSFT can be 305 km/h when the crosswind velocity is 20 m/s. The larger cargo density should be encouraged because it is good for train overturning safety in severe working conditions. [ABSTRACT FROM AUTHOR]

The acceleration of land desertification has led to an increasingly serious threat to the operation safety of tunnel entrance in the Gobi and desert regions by wind-sand flow, and it is urgent to study and enhance the running safety of train. Firstly, an ultrasonic anemometer is used to collect the characteristics of wind-sand flow at a tunnel entrance site in Xinjiang, China. Then, based on the Euler multiphase flow and the SST k-w model, the variation difference law of the train running at the tunnel entrance is revealed under the four inflow conditions of constant crosswind, constant wind-sand flow, pulsating crosswind and pulsating wind-sand flow respectively. Finally, the disturbance law of the solid wind barrier at the tunnel entrance on the wind-sand flow and the influence mechanism on the train's flow field structure and pressure are revealed. The results show that compared with other cases, the pulsating wind-sand flow has the most significant effect on the moving trains' aerodynamic loads (ALs), and the sand particles carried in the air cause the trains' ALs to fluctuate within 9.09%. The solid wind barrier has a significant disturbing effect on the wind-sand flow, and the lightweight sand particles follow the air flow over the top of the wind barrier and are not deposited on the embankment during a short period, and the wind-sand flow's impact on the HSTs is dramatically reduced. The wind barrier changes the HST's flow field, and the AL fluctuation of the train is sharply reduced. The maximum values of the head train's AL coefficients are reduced by 46.53-85.75%. [ABSTRACT FROM AUTHOR]