Dynamic characteristics of coal gangue subgrade filler under traffic load based on the hysteretic curves.

Traffic cyclic loading is the key factor that leads to the deterioration of the long-term service behavior of subgrade. A series of cyclic triaxial tests was carried out by the large-scale dynamic and static triaxial apparatus (LSDSTA) to study the dynamic behaviors of coal gangue subgrade filler (CGSF) under multi-step cyclic loading using the morphological characteristics of hysteretic curves (MCHC). MCHC was quantitatively characterized by four parameters, i.e., the unclosed degree (εphl), inclination of long axis degree (khl), area (Shl) and fullness degree (αhl). With the increase of dynamic strain, εphl increases exponentially. khl of the coal gangue sample first decreases and then shows an increasing trend with the increasing dynamic strain. The values of Shl are close to each other, and the energy dissipation in the sample is small. However, with the increase of dynamic strain, the specimen failure degree is increased, Shl increases exponentially, and the damping ratio increases. With the increase of dynamic strain, αhl increases approximately linearly. Confining pressure has a certain effect on the four parameters. There parameters can be recommended and used for quantitative analysis the dynamic behaviors of subgrade filler under traffic cyclic loading.

Charge-density wave mediated quasi-one-dimensional Kondo lattice in stripe-phase monolayer 1T-NbSe2.

The heavy fermion physics is dictated by subtle competing exchange interactions, posing a challenge to their understanding. One-dimensional (1D) Kondo lattice model has attracted special attention in theory, because of its exact solvability and expected unusual quantum criticality. However, such experimental material systems are extremely rare. Here, we demonstrate the realization of quasi-1D Kondo lattice behavior in a monolayer van der Waals crystal NbSe2, that is driven into a stripe phase via Se-deficient line defects. Spectroscopic imaging scanning tunneling microscopy measurements and first-principles calculations indicate that the stripe-phase NbSe2 undergoes a novel charge-density wave transition, creating a matrix of local magnetic moments. The Kondo lattice behavior is manifested as a Fano resonance at the Fermi energy that prevails the entire film with a high Kondo temperature. Importantly, coherent Kondo screening occurs only in the direction of the stripes. Upon approaching defects, the Fano resonance exhibits prominent spatial 1D oscillations along the stripe direction, reminiscent of Kondo holes in a quasi-1D Kondo lattice. Our findings provide a platform for exploring anisotropic Kondo lattice behavior in the monolayer limit.

circ_0029463 promotes osteoclast differentiation by mediating miR-134-5p/Rab27a axis.

OBJECTIVE: Osteoporosis is the imbalance in bone homeostasis between osteoblasts and osteoclasts. In this study, we investigated the effects of the circ_0029463/miR-134-5p/Rab27a axis on RANKL-induced osteoclast differentiation. METHODS: RT-qPCR and western blotting were used to detect the expression of circ_0029463, miR-134-5p, and Rab27a in tissues from patients with osteoporosis and in RANKL-induced osteoclasts. Osteoclast differentiation was verified by TRAP staining. Osteoclast biomarkers, including NFATc1, TRAP, and CTSK, were measured. The target and regulatory relationships between circ_0029463, miR-134-5p, and the Rab27a axis were verified using RIP, dual-luciferase reporter gene, and RNA pull-down assays. RESULTS: Elevated expression of circ_0029463 and Rab27a and decreased miR-134-5p expression were observed in the tissues of patients with osteoporosis, and a similar expression pattern was observed in RANKL-induced osteoclasts. Suppression of circ_0029463 expression or miR-134-5p overexpression curbed RANKL-induced osteoclast differentiation, whereas such an effect was abolished by Rab27 overexpression. circ_0029463 sponges miR-134-5p to induce Rab27a expression. CONCLUSION: circ_0029463 sponges miR-134-5p to abolish its suppressive effect of miR-134-5p on Rab27a expression, thereby promoting osteoclast differentiation.

Genomic insights into genetic diversity and local adaptation of a dominant desert steppe feather grass, Stipa breviflora Griseb.

Investigating the genetic mechanisms of local adaptation is critical to understanding how species adapt to heterogeneous environments. In the present study, we analyzed restriction site-associated DNA sequencing (RADseq) data in order to explore genetic diversity, genetic structure, genetic differentiation, and local adaptation of Stipa breviflora. In total, 135 individual plants were sequenced and 25,786 polymorphic loci were obtained. We found low genetic diversity (He = 0.1284) within populations of S. breviflora. Four genetic clusters were identified along its distribution range. The Mantel test, partial Mantel test, and multiple matrix regression with randomization (MMRR) indicate that population differentiation was caused by both geographic distance and environmental factors. Through the FST outlier test and environmental association analysis (EAA), 113 candidate loci were identified as putatively adaptive loci. RPK2 and CPRF1, which are associated with meristem maintenance and light responsiveness, respectively, were annotated. To explore the effects of climatic factors on genetic differentiation and local adaptation of S. breviflora, gradient forest (GF) analysis was applied to 25,786 single nucleotide polymorphisms (SNPs) and 113 candidate loci, respectively. The results showed that both temperature and precipitation affected the genetic differentiation of S. breviflora, and precipitation was strongly related to local adaptation. Our study provides a theoretical basis for understanding the local adaptation of S. breviflora.

p-AKT/VPS4B regulates the small extracellular vesicle size in venous malformation endothelial cells.

OBJECTIVE: Small extracellular vesicle (sEV)-mediated intercellular communication is increasingly the key for the understanding of venous malformations (VMs). This study aims to clarify the detailed changes of sEVs in VMs. SUBJECTS AND METHODS: Fifteen VM patients without treatment history and twelve healthy donors were enrolled in the study. sEVs were isolated from both fresh lesions and cell supernatant, and were examined by western blotting, nanoparticle tracking analysis and transmission electron microscopy. Western blot analysis, immunohistochemistry and immunofluorescence were adopted to screening candidate regulator of sEV size. Specific inhibitors and siRNA were employed to validate the role of dysregulated p-AKT/vacuolar protein sorting-associated protein 4B (VPS4B) signaling on the size of sEVs in endothelial cells. RESULTS: The size of sEVs derived from both VM lesion tissues and cell model was significantly increased. VPS4B, whose expression level was mostly significantly downregulated in VM endothelial cells, was responsible for the size change of sEVs. Targeting abnormal AKT activation corrected the size change of sEVs by recovering the expression level of VPS4B. CONCLUSION: Downregulated VPS4B in endothelial cells, resulted from abnormally activated AKT signaling, contributed to the increased size of sEVs in VMs.

Deciphering the Heterogeneity Landscape of Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles for Precise Selection in Translational Medicine.

Mesenchymal stem/stromal cell-derived extracellular vesicles (MSC-EVs) have been considered promising therapeutics for disease treatments. However, MSC-EVs harvested from different tissues present unique biological features reflective of their origins. The heterogeneity of MSC-EVs constitutes an important barrier to their precise application in clinical translation that may probably lead to uncertain therapeutic effects. To give hints for future clinical translation, five MSCs are employed, whose derived EVs are most intensively utilized, namely bone marrow mesenchymal stem/stromal cells (BMMSCs), umbilical cord stem/stromal cells (UCSCs), adipose-derived stem/stromal cells (ASCs), dermal stem/stromal cells (DSCs) and dental pulp stem/stromal cells (DPSCs) and the heterogeneity landscape of the corresponding MSC-EVs are documented. Overall, the basic parameters, stability, and biosafety of different MSC-EVs are indiscriminate. Strikingly, UCSC-EVs exhibit distinguishing productivity. UCSC-EVs as well as DPSC-EVs present better drug loading/delivery capacity. In addition, the heterogeneity of different MSC-EVs in cargo diversity, cellular affinity, organ biodistribution, and therapeutic effects may cue the rational selection in different disease treatments. Through a combined assessment, a rational strategy is combined for selecting MSC-EVs in future clinics. Offering a panoramic view of MSC-EVs harvested from different tissues, the current study may provide guidelines for the precise selection of MSC-EVs in next-generation therapeutics.

Adaptive Learning Control of Switched Strict-Feedback Nonlinear Systems With Dead Zone Using NN and DOB.

This article investigates the adaptive learning control for a class of switched strict-feedback nonlinear systems with external disturbances and input dead zone. To handle unknown nonlinearity and compound disturbances, a collaborative estimation learning strategy based on neural approximation and disturbance observation is proposed, and the adaptive neural switched control scheme is studied in a dynamic surface control framework. In the adaptive learning control design, to obtain the evaluation information of uncertain learning, the prediction error is constructed based on the composite learning scheme. Then, the prediction error and the compensated tracking error are applied to construct the adaptive laws of switched neural weights and switched disturbance observers. The system stability analysis is carried out through the Lyapunov approach, where the switching signal with average dwell time is considered. Through the simulation test, the effectiveness of the proposed adaptive learning controller is verified.

Fuzzy-Model-Based Lateral Control for Networked Autonomous Vehicle Systems Under Hybrid Cyber-Attacks.

This article addresses the problem of lateral control problem for networked-based autonomous vehicle systems. A novel solution is presented for nonlinear autonomous vehicles to smoothly follow the planned path under external disturbances and network-induced issues, such as cyber-attacks, time delays, and limited bandwidths. First, a fuzzy-model-based system is established to represent the nonlinear networked vehicle systems subject to hybrid cyber-attacks. To reduce the network burden and effects of cyber-attacks, an asynchronous resilient event-triggered scheme (ETS) is proposed. A dynamic output-feedback control method is developed to address the underlying problem. Conditions are derived to obtain the output-feedback controller and resilient asynchronous ETS such that the closed-loop switched fuzzy system is globally exponentially stable. Examples are provided to demonstrate the effectiveness and merits of the proposed new control design techniques.

A molecular phenotypic screen reveals that lobetyolin alleviates cardiac dysfunction in 5/6 nephrectomized mice by inhibiting osteopontin.

BACKGROUND: Cardiovascular diseases are the major cause of mortality in patients with advanced chronic kidney diseases. The predominant abnormality observed among this population is cardiac dysfunction secondary to myocardial remodelings, such as hypertrophy and fibrosis, emphasizing the need to develop potent therapies that maintain cardiac function in patients with end-stage renal disease. AIMS: To identify potential compounds and their targets as treatments for cardiorenal syndrome type 4 (CRS) using molecular phenotyping and in vivo/in vitro experiments. METHODS: Gene expression was assessed using bioinformatics and verified in animal experiments using 5/6 nephrectomized mice (NPM). Based on this information, a molecular phenotyping strategy was pursued to screen potential compounds. Picrosirius red staining, wheat germ agglutinin staining, Echocardiography, immunofluorescence staining, and real-time quantitative PCR (qPCR) were utilized to evaluate the effects of compounds on CRS in vivo. Furthermore, qPCR, immunofluorescence staining and flow cytometry were applied to assess the effects of these compounds on macrophages/cardiac fibroblasts/cardiomyocytes. RNA-Seq analysis was performed to locate the targets of the selected compounds. Western blotting was performed to validate the targets and mechanisms. The reversibility of these effects was tested by overexpressing Osteopontin (OPN). RESULTS: OPN expression increased more remarkably in individuals with uremia-induced cardiac dysfunction than in other cardiomyopathies. Lobetyolin (LBT) was identified in the compound screen, and it improved cardiac dysfunction and suppressed remodeling in NPM mice. Additionally, OPN modulated the effect of LBT on cardiac dysfunction in vivo and in vitro. Further experiments revealed that LBT suppressed OPN expression via the phosphorylation of c-Jun N-terminal protein kinase (JNK) signaling pathway. CONCLUSIONS: LBT improved CRS by inhibiting OPN expression through the JNK pathway. This study is the first to describe a cardioprotective effect of LBT and provides new insights into CRS drug discovery.

Zhen-Wu decoction and lactiflorin, an ingredient predicted by in silico modelling, alleviate uremia induced cardiac endothelial injury via Nrf2 activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Cardiorenal syndrome type 4 (CRS type 4), with high rates of morbidity and mortality, has become a social and economic problem worldwide over the last few decades. Zhen-Wu decoction, a traditional medicine used in East Asia, has been widely used in the treatment of cardiovascular disease and kidney disease, and has shown potential therapeutic effects for the clinical treatment of CRS type 4. However, the underlying mechanism has not been extensively explored. AIM OF THE STUDY: The purpose of this study was to investigate the effect and underlying mechanism of Zhen-Wu decoction on uremic cardiomyopathy, offering a potential target for clinical treatment of CRS type 4. MATERIALS AND METHODS: Five/six nephrectomized mice were utilized for experiments in vivo. The cardioprotective effects of Zhen-Wu decoction were evaluated by echocardiography and tissue staining. RNA-Seq data were used to investigate the potential pharmacological mechanism. The prediction of targets and active components was based on our previous strategy. Subsequently, the protective effect of the selected compound was verified in experiments in vitro. RESULTS: Zhen-Wu decoction alleviated cardiac dysfunction and endothelial injury in 5/6 nephrectomized mice, and the mechanism may involve the inflammatory process and oxidative stress. The activation of the Nrf2 signaling pathway was predicted to be a potential target of Zhen-Wu decoction in protecting endothelial cells. Through our machine learning strategy, we found that lactiflorin as an ingredient in Zhen-Wu decoction, alleviates IS-induced endothelial cell injury by blocking Keap1 and activating Nrf2. CONCLUSIONS: The present study demonstrated that Zhen-Wu decoction and lactiflorin could protect endothelial cells against oxidative stress in mice after nephrectomy by activating the Nrf2 signaling pathway.

Endothelial cells induce degradation of ECM through enhanced secretion of MMP14 carried on extracellular vesicles in venous malformation.

Venous malformations (VMs), featuring localized dilated veins, are the most common developmental vascular anomalies. Aberrantly organized perivascular extracellular matrix (ECM) is one of the prominent pathological hallmarks of VMs, accounting for vascular dysfunction. Although previous studies have revealed various proteins involved in ECM remodeling, the detailed pattern and molecular mechanisms underlying the endothelium-ECM interplay have not been fully elucidated. Our previous studies revealed drastically elevated extracellular vesicle (EV) secretion in VM lesions. Here, we identified increased EV-carried MMP14 in lesion fluids of VMs and culture medium of TIE2-L914F mutant endothelial cells (ECs), along with stronger ECM degradation. Knockdown of RAB27A, a required regulator for vesicle docking and fusion, led to decreased secretion of EV-carried MMP14 in vitro. Histochemical analysis further demonstrated a highly positive correlation between RAB27A in the endothelium and MMP14 in the perivascular environment. Therefore, our results proved that RAB27A-regulated secretion of EV-MMP14, as a new pattern of endothelium-ECM interplay, contributed to the development of VMs by promoting ECM degradation.

[Innovation and development of Chinese Osteosynthesis].

Chinese Osteosynthesis is a fracture treatment system of integrated Traditional Chinese medicine and Western medicine.Starting from our country reality, according to the traditional theory, highlight the characteristics of traditional Chinese medicine and using modern science and technology, under the guidance of the new fracture treatment principles, after a lot of clinical practice and continuous summary, the integrated Chinese and western medicine fracture treatment system with manual reduction and local external fixation is formed.This paper systematically reviews its development history, which provides enlightenment for our innovation and development today.

[Tetrahydropalmatine alleviated diabetic neuropathic pain by inhibiting activation of microglia via p38 MAPK signaling pathway].

Neuropathic pain is one of the common complications of diabetes. Tetrahydropalmatine(THP) is a main active component of Corydalis Rhizoma with excellent anti-inflammatory and pain-alleviating properties. This study aims to investigate the therapeutic effect of THP on diabetic neuropathic pain(DNP) and the underlying mechanism. High-fat and high-sugar diet(4 weeks) and streptozotocin(STZ, 35 mg·kg~(-1), single intraperitoneal injection) were employed to induce type-2 DNP in rats. Moreover, lipopolysaccharide(LPS) was used to induce the activation of BV2 microglia in vitro to establish an inflammatory cellular model. Fasting blood glucose(FBG) was measured by a blood glucose meter. Mechanical withdrawal threshold(MWT) was assessed with von Frey filaments, and thermal withdrawal latency(TWL) with hot plate apparatus. The protein expression levels of OX42, inducible nitric oxide synthase(iNOS), CD206, p38, and p-p38 were determined by Western blot, the fluorescence expression levels of OX42 and p-p38 in the dorsal horn of the rat spinal cord by immunofluorescence, the mRNA content of p38 and OX42 in rat spinal cord tissue by qRT-PCR, and levels of nitric oxide(NO), interleukin-1ß(IL-1ß), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), interleukin-10(IL-10), and serum fasting insulin(FINS) by enzyme-linked immunosorbent assay(ELISA). RESULTS:: showed that the mo-del group demonstrated significant decrease in MWT and TWL, with pain symptoms. THP significantly improved the MWT and TWL of DNP rats, inhibited the activation of microglia and p38 MAPK signaling pathway in rat spinal cord, and ameliorated its inflammatory response. Meanwhile, THP promoted the change of LPS-induced BV2 microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, suppressed the activation of the p38 MAPK signaling pathway, decreased the expression levels of inflammatory factors NO, IL-1ß, IL-6, and TNF-α, and increased the expression level of anti-inflammatory factor IL-10. The findings suggested that THP can significantly ameliorate the pain symptoms of DNP rats possibly by inhibiting the inflammatory response caused by M1 polarization of microglia via the p38 MAPK pathway.

Single-crystal superprotonic conductivity in an interpenetrated hydrogen-bonded quadruplex framework.

A proton-transporting pathway is crucial to the conduction mechanism in fuel cells and biological systems. Here, we report a novel 5-fold interpenetrated three-dimensional (3D) hydrogen-bonded quadruplex framework, which exhibits an ultrahigh single-crystal proton conductivity of 1.2(1) × 10-2 S cm-1 at 95 °C and 98% relative humidity, benefitting from the spiral H3O+/H2O chains in 1D pore channels studded with COOH/COO- groups.

[Intraoperative arthrography monitoring assisted closed reduction and internal fixation for intercondylar fracture of humerus in children].

OBJECTIVE: To investigate clinical effects of intraoperative arthrography monitoring assisted closed reduction and internal fixation for intercondylar fracture of humerus in children. METHODS: From January 2013 to July 2018, 18 children with intercondylar fracture of humerus were treated by operation, including 13 males and 5 females aged from 3 to 12 years old with an average age of (8.50±2.57) years old. According to Toniolo & Wilkinson classification, 8 children were typeⅠand 10 children were typeⅡ. During the operation, closed reduction and internal fixation were performed under the monitoring of intraoperative radiography, open reduction and internal fixation were performed in necessity. Mayo score of elbow joint was used to evaluate clinical effect at 6 months after operation. RESULTS: All children were underwent arthrography monitoring during operation, 5 children were treated with closed reduction and internal fixation for intraoperative arthrography found no fracture of articular cartilage, 11 children by closed reduction and internal fixation because of fracture of articular cartilage involving the joint space with displacement less than 2 mm, and 2 children by closed or open reduction and internal fixation for fracture of articular cartilage surface with displacement above 2 mm, which 1 child with smooth of joint surface was performed closed reduction and internal fixation, 1 child without smooth of joint surface and displacement above 2 mm was performed open reduction and internal fixation. All children were followed up from 8 to 26 months with an average of (20.28±4.40) months. All factures were healed from 6 to 9 weeks with an average of (7.33±0.77) weeks. Postoperative Mayo score of elbowjoint at 6 months was (89.44±11.36), and 12 patients got excellent results, 5 good and 1 poor. One patient occurred partial limitation of flexion or extension of elbow joint. No elbow deformity and other complications occurred. CONCLUSION: The treatment of intercondylar fracture of humerus in children under monitoring of intraoperative radiography could reduce opertaion injuries and complications, confirm the reduction effect of articular surface of cartilage in time and clearly, and promote recovery of elbow joint function.

[Evidence mapping of clinical research on 28 Chinese patent medicines for tension-type headache].

In this study, the evidence mapping methodology was used to systematically retrieve and sort out the clinical research evidence of Chinese patent medicines in the treatment of tension-type headache(TTH), and to understand the distribution of evidence in this field and the basis and quality of evidence. Chinese and English articles on the 28 Chinese patent medicines for TTH, which were recorded in National Essential Medicines List(2018), Medicine Catalogue for National Basic Medical Insurance, Work Injury Insurance, and Maternity Insurance(2020), and Chinese Pharmacopoeia(2020), were retrieved from China National Knowledge Infrastructure(CNKI), Wanfang, VIP, China Biology Medicine disc(CBMdisc), PubMed, EMbase, and Cochrane Library from the establishment to June 2021, followed by descriptive analysis. Then, tables and bubble charts were plotted to analyze the distribution characteristics of evidence. A total of 129 eligible articles were yielded: 126 randomized/non-randomized controlled trials, and 3 systematic reviews. The functions, indications, and composition of the 28 medicines, as well as the proportion of related articles, publication trends, intervention measures, and outcome indicators were compared and analyzed. The results showed that the 28 Chinese patent medicines, composed of 128 Chinese medicinals, can be classified into six categories in terms of function: reinforcing healthy Qi, tranquilizing mind, dispelling stasis, regulating Qi, treating wind, and resuscitating. There are ongoing efforts to study the treatment of TTH with Chinese patent medicine in China, despite of little evidence. The clinical positioning of Chinese patent medicine for TTH is not clear, and clinical research fails to highlight the advantages of Chinese medicine. In addition, the outcome indicators have not been standardized and unified, and there is a lack of evidence on the long-term efficacy of Chinese patent medicine for TTH. This study is the first exploratory application of evidence maps to compare the characteristics and clinical research progress of 28 Chinese patent medicines for TTH, which can provide a reference for research on the optimization of Chinese medicine strategies for TTH.

[Effects of low intensity resistance training of blood flow restriction with different occlusion pressure on lower limb muscle and cardiopulmonary function of college students].

Objective: The study compared the effects of low intensity resistance training with blood flow restriction (BFR) with different occlusion pressure on lower limb muscle and cardiopulmonary function. Methods: Twenty-seven college students were randomly divided into three groups by different occlusion pressure: 0 mmHg (group C), 120 mmHg (group L) and 180 mmHg (group H). Before and after training (3 times a week for 12 weeks) with an inflatable cuff (20% 1RM, half squat), the muscle thickness(MTH)of rectus femoris and medius femoris, relative peak knee extensor moment(rM), peak power(P), relative maximal oxygen uptake(rVO2max), stroke volume(SV), cardiac output(CO), ejection fraction(EF) and other indicators were measured for all subjects. Results: When compared with pre-training, and rectus femoris, the MTH of medius femoris, rM, rVO2max, SV, CO and EF were significantly increased in group L and group H after 12 weeks training(P＜0.05, P＜0.01), as well as compared with group C after training(P＜0.05, P＜0.01). There was no significant difference between group L and group H after training. Conclusion: BFR training protocols under 120 mmHg or 180 mmHg pressure were effective in improving muscle and cardiopulmonary function.