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Objectives: To explore the correlation and significance of serum insulin-like growth factor-1 (IGF-1) and bone metabolism markers in patients with non-traumatic avascular necrosis of femoral head (N-ANFH). Methods: A prospective study was conducted on the patients with control and N-ANFH cohorts admitted from the orthopedic department of The Sixth Affiliated Hospital of Guangzhou Medical University from July 2020 to February 2023. The control (n=25) and N-ANFH cohorts (n=30) were randomly selected using block randomization method. The gender, age, body mass index (BMI), IGF-1, bone metabolism markers, including type I collagen hydroxyl terminal peptide β special sequence (β-CTX), N-terminal mid-fragment of osteocalcin (N-MID), total aminoterminal propeptide of type I procollagen (T-PINP), serum 25-hydroxyvitamin (D25(OH)D), parathormone and bone density, were compared between the two cohorts. Single and multiple factor logistic regression analysis were applied to study the correlation between dependent variable and N-ANFH. The expression pattern of IGF-1 in bone tissue from control and N-ANFH cohorts was detected by immunofluorescence (IF). Bone mineral density (BMD) was evaluated by dual-energy X-ray absorptiometry (DXA) scanning. Pearson correlation analysis was used to analyze the relationship between IGF-1 and BMD, the value of IGF-1 in the diagnosis N-ANFH was evaluated by receiver operating characteristic curve (ROC) analysis. Results: The bone metabolism markers of the control cohort were significantly higher than those of the N-ANFH cohort (p< 0.05), and IF revealed that the expression level of IGF-1 in the control cohort was significantly higher than that of the N-ANFH cohort. The expression level of IGF-1 was positively correlated with hip BMD (r= 0.7569, p= 0.0001). The area under ROC curve (AUC) in the diagnosis of N-ANFH was 0.7373, p= 0.0026, with a cutoff value of 139.6, corresponding sensitivity of 80%, and a specificity of 64%. Conclusion: The bone metabolism level of N-ANFH is significantly reduced, and IGF-1 is not only closely related to the level of osteoporosis, but also one of vital biomarkers for diagnosing N-ANFH, suggesting that decreased bone metabolism level and osteoporosis may be the main causes of N-ANFH.

Isofurans (IsoFs) are a series of novel discovered lipid peroxidation products. This study focused on the investigation of the angiogenic property of IsoF. MTT stain assay indicated that 1 µm IsoF had the most bioactivity in rat brain endothelial cells (RBECs). IsoF significantly promoted cellular proliferation and migration and remarkably decreased staurosporine-induced apoptosis by TUNEL assay in the RBECs. It successfully up-regulated rat aortic vascularization and choroid explant sprouting, extracellular regulated protein kinases (ERK)1/2, and triggered calcium release. RT-PCR examination indicated that IsoF up-regulated tumor necrosis factor (TNF)α, angiopoietin-1 receptor (Tie2), and vascular endothelial growth factor (VEGF)-A, but did not interfere with caspase 2 and VEGF-C in the RBECs. IsoF has pro-angiogenic activity. Calcium release and ERK1/2 phosphorylation may be involved in the signaling of the IsoF-induced up-regulation of TNFα, Tie2, and VEGF-A, which could be the molecular mechanism of the pro-angiogenic activity of the IsoF.

Spine–pelvis–lower extremity sagittal alignment is regarded as a global sagittal balance. Currently, there are few studies evaluating the pelvic and femoral sagittal alignment during total knee arthroplasty (TKA). This retrospective study aims to elucidate how pelvic and femoral sagittal alignment affect clinical outcomes of primary TKA for osteoarthritis (OA) and determine the proper range of femoral sagittal alignment. Patient-reported outcome measures (PROMs), including the Knee Society Score (KSS), Western Ontario and McMaster Universities (WOMAC), and patient satisfaction scores, and clinician-reported outcomes (CROs), including range of motion (ROM) and pelvic and femoral sagittal parameters, of 67 cases were evaluated (89 knees) before and 1 year after TKA. The angle between the distal femur anterior cortex line and flange of the femoral component (FC) was defined as the α angle. Correlations between the α angle and PROM and CRO were investigated using multivariate and secondary regression analyses. Patients were further divided into four cohorts (A, B, C, and D) according to the α angle, and comparisons of their postoperative PROM and ROM scores were performed. Postoperative PROM and ROM scores improved significantly compared with the preoperative scores (p

Background: Isofurans (IsoFs) are a series of novel discovered lipid peroxidation products, which are found in some oxidation-injured disorders. Oxidative damage is a major pathological feature of abnormal vascularization diseases. This study is focused on the investigation of angiogenic property of IsoF. The alteration on cellular proliferation, migration, and apoptosis by an IsoF were also detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, coverslip migration assay, and TUNEL assay. Furthermore, cellular calcium release and extracellular regulated protein kinases (ERK) 1/2 activation by IsoF were analyzed. RT-PCR was carried out to detect some angiogenesis-related gene expression induced by IsoF. Results: MTT stain assay indicated that 1mM IsoF had the most bioactivity in RBECs. IsoF significantly promoted cellular proliferation and migration and remarkably decreased staurosporine-induced apoptosis by TUNEL assay in the RBECs. Moreover, IsoF activated extracellular regulated protein kinases (ERK)1/2 and trigged calcium release. RT-PCR examination indicated that IsoF up-regulated tumor necrosis factor (TNF)a, angiopoietin-1 receptor (Tie2), and vascular endothelial growth factor (VEGF)-A, but did not interfere with caspase 2 and VEGF-C in the RBECs.Conclusion: IsoF has pro-angiogenic activity via promotion of cellular proliferation/migration and prohibition of cellular apoptosis. Calcium release and ERK1/2 phosphorylation may be involved in the signaling of the IsoF-induced up-regulation of TNFa, Tie2, and VEGF-A, which could be the molecular mechanism of the pro-angiogenic activity of the IsoF.

Thin-ply composite failure modes also significantly differ from conventional ply composite failure modes, with the final failure mechanism switching from irregular progressive failure to direct fracture characterized by a uniform fracture with the reduction of the ply thickness. When open holes and bolt joints are involved, thin-ply-laminated composites exhibit more complex stress states, damage evolution, and failure modes. Compared to the experimental study of thin-ply-laminated composite-bolted joints, there are few reports about numerical analysis. In order to understand the damage evolution and failure mechanism of thin-ply-laminated composites jointed by single-lap bolt, a progressive damage model based on three-dimensional (3D) LaRC failure criterion combined with cohesive element is constructed. Through an energy-based damage evolution method, this model can capture some significant mechanical characteristics in thin-ply-laminated structures, such as the in situ effect, delamination inhibition, and fiber compressive kinking failure. The comparisons between the numerical predictions and experimental observations are made to verify the accuracy of the proposed model. It is found that the predicted stress-displacement curves, failure modes, damage morphologies, etc., are consistent with the experimental results, indicating that the presented progressive damage analysis method displays excellent accuracy. The predicted stress at the onset of delamination is 50% higher than that of the conventional thick materials, which is also consistent with experimental results. Moreover, the numerical model provides evidence that the microstructure of thin-ply-laminated composite performs better in uniformity, which is more conducive to inhibiting the intra-layer damage and the expansion of delamination damage between layers. This study on the damage inhibition mechanism of thin-ply provides a potential analytical tool for evaluating damage tolerance and bearing capabilities in thin-ply-laminated composite-bolted joints.

Quantitation of rare somatic mutations is essential for basic research and translational clinical applications including minimal residual disease (MRD) detection. Though unique molecular identifier (UMI) has suppressed errors for rare mutation detection, the sequencing depth requirement is high. Here, we present Quantitative Blocker Displacement Amplification (QBDA) which integrates sequence-selective variant enrichment into UMI quantitation for accurate quantitation of mutations below 0.01% VAF at only 23,000X depth. Using a panel of 20 genes recurrently altered in acute myeloid leukemia, we demonstrate quantitation of various mutations including single base substitutions and indels down to 0.001% VAF at a single locus with less than 4 million sequencing reads, allowing sensitive MRD detection in patients during complete remission. In a pan-cancer panel and a melanoma hotspot panel, we detect mutations down to 0.1% VAF using only 1 million reads. QBDA provides a convenient and versatile method for sensitive mutation quantitation using low-depth sequencing., Quantification of rare somatic mutations is essential for basic research and translational applications. Here the authors present Quantitative Blocker Displacement Amplification allowing for accurate detection of mutations below 0.01% VAF.

Current gold standard for absolute quantitation of a specific DNA sequence is droplet digital PCR (ddPCR), which has been applied to copy number variation (CNV) detection. However, the number of quantitation modules in ddPCR is limited by fluorescence channels, which thus limits the CNV sensitivity due to sampling error following Poisson distribution. Here we develop a PCR-based molecular barcoding NGS approach, quantitative amplicon sequencing (QASeq), for accurate absolute quantitation scalable to over 200 quantitation modules. By attaching barcodes to individual target molecules with high efficiency, 2-plex QASeq exhibits higher and more consistent conversion yield than ddPCR in absolute molecule count quantitation. Multiplexed QASeq improves CNV sensitivity allowing confident distinguishment of 2.05 ploidy from normal 2.00 ploidy. We apply multiplexed QASeq to serial longitudinal plasma cfDNA samples from patients with metastatic ERBB2+ (HER2+ ) breast cancer seeking association with tumor progression. We further show an RNA QASeq panel for targeted expression profiling.

In recent years, nanomaterials and nanotechnology have emerged as vital factors in the medical field with a unique contribution to cancer medicine. Given the increasing number of cancer patients, it is necessarily required to develop innovative strategies and therapeutic modalities to tackle hypoxia, which forms a hallmark and great barrier in treating solid tumors. The present review details the challenges in nanotechnology-based hypoxia, targeting the strategies and solutions for better therapeutic performances. The interaction between hypoxia and tumor is firstly introduced. Then, we review the recently developed engineered nanomaterials towards multimodal hypoxia tumor therapies, including chemotherapy, radiotherapy, and sonodynamic treatment. In the next part, we summarize the nanotechnology-based strategies for overcoming hypoxia problems. Finally, current challenges and future directions are proposed for successfully overcoming the hypoxia tumor problems.

Study Design In vitro biomechanical analysis. Objectives Compare the destabilizing effects of anterior discectomy to posterior spinal releases. Summary of Background Data Posterior release and pedicle screw fixation has become the accepted form of treatment for lumbar and thoracolumbar pediatric scoliotic spinal deformity. A biomechanical evaluation of posterior releases with comparison to traditional anterior releases has not been reported in the lumbar spine. Methods Eleven fresh-frozen human thoracolumbar specimens (T9–L5) were tested by a robotic manipulator (Staubli RX90; moment target of 5.0 Nm, force target of 50 N) in axial rotation (AR), plus lateral and anterior translation (LT and AT). Specimens underwent either sequential anterior release (partial and full discectomy) or posterior release (inferior facetectomy and wide posterior release) from T10 to L4. Partial discectomy retained the posterior 50% of disc and posterior longitudinal ligament, whereas full discectomy removed all of the disc and PLL. Wide posterior release included total facetectomy plus ligamentum flavum and spinous process resection. Results Inferior facetectomy produced an average increase of 1.5° ± 1.0° (p = .0625), 1.0 ± 0.8 mm (p = .0313), and 0.2 ± 0.3 mm (p = .156) in AR, LT, and AT, respectively. Compared with partial facetectomy, wide posterior release produced an average additional increase of 8.1° ± 4.0° (p = .0312), 2.0 ± 2.2 mm (p = .4062), and 1.1 ± 1.0 mm (p = .0625) in AR, LT, and AT, respectively. Full discectomy produced 201%, 161%, and 153% of the motion relative to wide posterior release in AR, LT, and AT, respectively (p = .0043, .0087, and .0173). Partial discectomy and wide posterior release proved statistically equivalent. Conclusions Wide posterior release of the thoracolumbar spine allows significant correction and may be superior to inferior facetectomy in axial rotation. Although complete discectomy with PLL resection would likely allow greater correction, a more clinically realistic partial discectomy confers similar corrective potential in vitro compared with wide posterior release. Level of Evidence Not applicable.

Two kinds of competition between different Heusler structure types are explored. The first is the competition between XA and L21 structures based on the cubic system of full-Heusler alloys of Pd2 YZ and the second is the competitive mechanism between the L21 cubic system and its L10 tetragonal system., In this work, two kinds of competition between different Heusler structure types are considered, one is the competition between XA and L21 structures based on the cubic system of full-Heusler alloys, Pd2 YZ (Y = Co, Fe, Mn; Z = B, Al, Ga, In, Tl, Si, Ge, Sn, Pb, P, As, Sb). Most alloys prefer the L21 structure; that is, Pd atoms tend to occupy the a (0, 0, 0) and c (0.5, 0.5, 0.5) Wyckoff sites, the Y atom is generally located at site b (0.25, 0.25, 0.25), and the main group element Z has a preference for site d (0.75, 0.75, 0.75), meeting the well known site-preference rule. The difference between these two cubic structures in terms of their magnetic and electronic properties is illustrated further by their phonon dispersion and density-of-states curves. The second type of competition that was subjected to systematic study was the competitive mechanism between the L21 cubic system and its L10 tetragonal system. A series of potential tetragonal distortions in cubic full-Heusler alloys (Pd2 YZ) have been predicted in this work. The valley-and-peak structure at, or in the vicinity of, the Fermi level in both spin channels is mainly attributed to the tetragonal ground states according to the density-of-states analysis. ΔE M is defined as the difference between the most stable energy values of the cubic and tetragonal states; the larger the value, the easier the occurrence of tetragonal distortion, and the corresponding tetragonal structure is stable. Compared with the ΔE M values of classic Mn2-based tetragonal Heusler alloys, the ΔE M values of most Pd2CoZ alloys in this study indicate that they can overcome the energy barriers between cubic and tetragonal states, and possess possible tetragonal transformations. The uniform strain has also been taken into consideration to further investigate the tetragonal distortion of these alloys in detail. This work aims to provide guidance for researchers to further explore and study new magnetic functional tetragonal materials among the full-Heusler alloys.

Introduction Ubiquitously found in all life forms, inorganic polyphosphates (polyP) are linear polymers of repeated orthophosphate units. Present in intervertebral disc tissue, polyP was previously shown to increase extracellular matrix production in nucleus pulposus (NP) cells. However, the effects of polyP on human annulus fibrosus (hAF) cell metabolism is not known. Methods and Results Here, hAF cells cultured in the presence of 0.5 to 1 mM polyP, chain length 22 (polyP‐22), showed an increase in glycosaminoglycan content, proteoglycan and collagen synthesis, and aggrecan and collagen type 1 gene expression. Gene expression level of matrix metalloproteinases 1 was reduced while matrix metalloproteinases 3 level was increased in hAF cells treated with 1 mM polyP. Adenosine triphosphate (ATP) synthesis was also significantly increased in hAF cell culture 72 hours after the exposure to 1 mM polyP‐22. Conclusions PolyP thus has both anabolic and bioenergetic effects in AF cells, similar to that observed in NP cells. Together, these results suggest polyP as a potential energy source and a metabolic regulator of disc cells., The current study investigates the effect of inorganic polyphosphates (polyPs) on human annulus fibrosus (AF) cell biology. This is a first study of its kind to investigate the effect of polyPs on human AF cells. polyPs, rich in polyanhydride bonds and known donors of phosphate molecule for ATP synthesis, showed increase in matrix production and ATP generation in human AF cells and overall promoted anabolism.

Most of the existing robots would find it difficult to stretch and transform all parts of their body together due to rigid components and complex actuation mechanisms inside. Here, we presented a highly transformable liquid-metal composite (LMC) that is easy to change shape in large magnitude and resume its original state again according to need. When subject to heating, part of the ethanol droplets embedded in the composite would change phase and then actuate. We demonstrate the flexible transformation of LMC-made octopus from a two-dimensional shape into several predictable three-dimensional shapes freely on a large scale (even up to 11 times its initial height) through remote wireless heating, which needs no sophisticated operating system at all. Further, several designed behaviors, such as movement of octopus and entangling objects of soft robots, are also realized. Theoretical analysis of the heating-induced liquid-vapor transition of the embedded ethanol droplet interprets the mechanisms involved. The present findings open a new way to fabricate functional transformable composites that would find significant applications in developing future generation soft robots.

Due to their prominent physicochemical properties, 2D materials are broadly applied in biomedicine. Currently, 2D materials have achieved great success in treating many diseases such as cancer and tissue engineering as well as bone therapy. Based on their different characteristics, 2D materials could function in various ways in different bone diseases. Herein, the application of 2D materials in bone tissue engineering, joint lubrication, infection of orthopedic implants, bone tumors, and osteoarthritis are firstly reviewed comprehensively together. Meanwhile, different mechanisms by which 2D materials function in each disease reviewed below are also reviewed in detail, which in turn reveals the versatile functions and application of 2D materials. At last, the outlook on how to further broaden applications of 2D materials in bone therapies based on their excellent properties is also discussed.

This case demonstrates an award-winning performance improvement project conducted by a large state-owned enterprise in China that satisfies the 10 standards of performance improvement and adds value to the organization. Multiple tools developed by performance improvement professionals in China are used to develop and implement marketing strategies and achieve market share improvement goals. These tools are based on the performance improvement literature, specifically designed for and empirically tested in the Chinese market. The case also shows benefits and challenges associated with integrating performance improvement and marketing management.

Materials with a temperature-controlled reversible electrical transition between insulator and conductor are attracting huge attention due to their promising applications in many fields. However, most of them are intrinsically rigid and require complicated fabrication processes. Here, a highly stretchable (680% strain) liquid metal polymer composite as a reversible transitional insulator and conductor (TIC), which is accompanied with huge resistivity changes (more than 4 × 109 times) reversibly through a tuning temperature in a few seconds is introduced. When frozen, the insulated TIC becomes conductive and recovers after warming. Both the phase change of the liquid metal droplets and the rigidity change of the polymer contribute directly to transition between insulator and conductor. A simplified model is established to predict the expansion and connection of liquid metal droplets. Along with high stretchability, straightforward fabrication methods, rapid triggering time, large switching ratio, good repeatability, the TIC offers tremendous possibilities for numerous applications, like stretchable switches, semiconductors, temperature sensors, and resistive random-access memory. Accordingly, a system that can display numbers and letters via converting alternative TIC temperature to a binary signal on a computer is conceived and demonstrated. The present discovery suggests a general strategy for fabricating and stimulating a stretchable transitional insulator and conductor based on liquid metal and allied polymers.

Cyborgs describe engineering human organisms with mechanical and electronic components to achieve human capacity enhancement. The past few decades have witnessed fascinating scientific endeavors to turn cyborgs from conceptual incubation stage into reality. Continuous advancements of a group of latest functional materials characterized by outstanding mechanical conformability with curvilinear human bodies, are bringing revolutions to cybernetic systems. Among them, liquid metals (LMs), as emerging classes of such important material candidates, have increasingly attracted special attentions in diverse fields spanning from biomedicine, human-machine interface to soft robotics and bioelectronics, attributed to their combined features of intrinsic fluidity, favorable conductivity, and benign biosafety. Especially, LMs open significant opportunity as highly conformable electronics for health-care monitoring, diagnosis, therapeutics, biological function enhancement, and brain-machine interaction. This perspective review is dedicated to outline the network of LM enabled cybernetic electronics from outside to inside of human bodies for patients or healthy persons, including wearable, attachable and implantable methodologies. The unique characteristics and special applied technologies of LMs are summarized and the future outlooks with key challenges of LM-enabled cybernetic electronics, are prospected.

The aim of this study was to investigate the effect of folic acid (FA) on tetrahydrobiopterin (BH4), neopterin, nitric oxide (NO) and homocysteine (Hcy) levels in endothelial cells. Human umbilical vein endothelial cells (HUVECs) were cultured in vitro in the presence or absence of Hcy. The effect of various doses of FA on Hcy, BH4, neopterin and NO concentrations in HUVECs was then assessed. In the 5 and 10 nmol/l FA treatment groups, FA was found to significantly increase the levels of BH4 (10.56±3.86 and 11.23±2.1919 pmol/g vs 6.32+2.87 nmol/g; P

This paper mainly studies the welding of stainless steel 321 and carbon steel Q245R dissimilar steel. Welding tests of stainless steel 321 and carbon steel Q245R are carried out by A-TIG welding method. The effect of active agent on weld penetration, weld formation and inner hole slag inclusion is studied. The mechanical properties of welded joints is measured by tensile and bending mechanics tests, and the macroscopic and microscopic structures are observed. Furthermore, these tests and research results are compared with conventional TIG welding. The results show that the welding of dissimilar steel with A-TIG welding method is well formed, and there are no pores, cracks and slag inclusion in the weld. The weld microstructure of the two welding methods is mainly austenite and ferrite. In the Q245R side heat affected zone (HAZ), the migration of carbon elements is obvious, but the A-TIG welding joint is superior to the conventional TIG welding in strength and toughness.

In this paper, a Prandtl-Ishlinskii hysteresis model (PI) is used to build a rate-independent hysteresis model for a class of conducting polymer actuators typified by tri-layer conjugated polymer actuators. Firstly, an off-line method is proposed to identify a discretization density function for the hysteresis model, and then a linear transfer function for the actuator is identified using the PI inverse model. Secondly, a neural network approach is proposed to realize an adaptive on-line identification method for the density function of the PI hysteresis model. In the back propagation (BP) algorithm for the neural network, the discretization PI operator is considered as an operational function of the neural network and the density function is considered as the power value. Finally, the simulation and experimental results are presented to demonstrate the validity of the model identification method and the actuator model.

Giant magnetostrictive material (GMM) is gathering more interests due to its superior electromechanical properties. Though the strain of GMM is almost larger than PZT, it still needs to be amplified to match practical demands. A press-bend amplification based giant magnetostrictive actuator (GMA) is designed and the electromechanical system model is presented. The dynamic model consists of two subsystems, one is a rate-independent hysteretic model and the other is a linear transfer function. The Duhem hysteresis model was employed for analyzing of the hysteresis phenomena in the GMA. Based on thoroughly discussion of the properties of Duhem model, an adaptive variable structure controller was designed, which guaranteed global stability of the control system with certain accuracy of tracking desired trajectories. Both simulation and experiment results verified the effectiveness of the proposed electromechanical model and the applicable of the extracted control method.

Compared with PZT, the actuating circuit of giant magnetostrictive material (GMM) is easier to implement in engineering for its lower supply voltage. Though the strain of GMM is almost larger than PZT, it also needs to be amplified for practical applications. A press-bend amplification based giant magnetostrictive actuator (GMA) is designed for testing. The electromechanical system model for the GMA is presented, which consists of two subsystems, one is a rate-independent hysteretic model and the other is a linear transfer function with no hysteretic effect. The Prandtl-Ishlinskii (PI) model was employed for analyzing of the hysteresis in the GMA. Based on thoroughly discussion of the Prandtl-Ishlinskii model, an adaptive variable structure controller was designed, which ensured global stability of the control system and certain accuracy of tracking a desired trajectory. Both simulation and experiment results verified the correctness of the electromechanical model and the applicable of the proposed control method.

Conducting polymer actuators are biocompatible with a small footprint, and operate in air or liquid media under low actuation voltages. This makes them excellent actuators for macroand micro-manipulation devices, however, their positioning ability or accuracy is adversely affected by their hysteresis non-linearity under open-loop control strategies. In this paper, we establish a hysteresis model for conducting polymer actuators, based on a rate-independent hysteresis model known as the Duhem model. The hysteresis model is experimentally identified and integrated with the linear dynamics of the actuator. This combined model is inverted to control the displacement of the tri-layer actuators considered in this study, without using any external feedback. The inversion requires an inverse hysteresis model which was experimentally identified using an inverse neural network model. Experimental results show that the position tracking errors are reduced by more than 50% when the hysteresis inverse model is incorporated into an inversion-based feedforward controller, indicating the potential of the proposed method in enabling wider use of such smart actuators.

This paper proposes an adaptive sliding mode control methodology to enhance the positioning ability of conducting polymer actuators typified by tri-layer conjugated polymer actuators. This is motivated by the search for an effective control strategy to command such actuators to a desired configuration in the presence of parametric uncertainties and unmodeled disturbances. After analyzing the stability of the adaptive sliding mode control system, experiments were conducted to demonstrate its satisfactory tracking ability, based on a series of experimental results. Implementation of the control law requires a valid model of the conducting polymer actuator and boundaries of the uncertainties and disturbances. Based on the theoretical and experimental results presented, the adaptive sliding mode control methodology is very attractive in the field of smart actuators which contain significant uncertainties and disturbances.