Mechanistic Insight Into the Roles of Integrins in Osteoarthritis

Osteoarthritis (OA), one of the most common degenerative diseases, is characterized by progressive degeneration of the articular cartilage and subchondral bone, as well as the synovium. Integrins, comprising a family of heterodimeric transmembrane proteins containing α subunit and β subunit, play essential roles in various physiological functions of cells, such as cell attachment, movement, growth, differentiation, and mechanical signal conduction. Previous studies have shown that integrin dysfunction is involved in OA pathogenesis. This review article focuses on the roles of integrins in OA, especially in OA cartilage, subchondral bone and the synovium. A clear understanding of these roles may influence the future development of treatments for OA

Cold in-place recycling asphalt mixtures: Laboratory performance and preliminary m-e design analysis

Cold in-place recycling (CIR) asphalt mixtures are an attractive eco-friendly method for rehabilitating asphalt pavement. However, the on-site CIR asphalt mixture generally has a high air void because of the moisture content during construction, and the moisture susceptibility is vital for estimating the road service life. Therefore, the main purpose of this research is to characterize the effect of moisture on the high-temperature and low-temperature performance of a CIR asphalt mixture to predict CIR pavement distress based on a mechanistic–empirical (M-E) pavement de-sign. Moisture conditioning was simulated by the moisture-induced stress tester (MIST). The moisture susceptibility performance of the CIR asphalt mixture (pre-mist and post-mist) was estimated by a dynamic modulus test and a disk-shaped compact tension (DCT) test. In addition, the standard solvent extraction test was used to obtain the reclaimed asphalt pavement (RAP) and CIR asphalt. Asphalt binder performance, including higher temperature and medium temperature performance, was evaluated by dynamic shear rheometer (DSR) equipment and low-temperature properties were estimated by the asphalt binder cracking device (ABCD). Then the predicted pavement distresses were estimated based on the pavement M-E design method. The experimental results revealed that (1) DCT and dynamic modulus tests are sensitive to moisture conditioning. The dynamic modulus decreased by 13% to 43% at various temperatures and frequencies, and the low-temperature cracking energy decreased by 20%. (2) RAP asphalt incorporated with asphalt emulsion decreased the high-temperature rutting resistance but improved the low-temperature anti-cracking and the fatigue life. The M-E design results showed that the RAP incorporated with asphalt emulsion reduced the international roughness index (IRI) and AC bottom-up fatigue pre-dictions, while increasing the total rutting and AC rutting predictions. The moisture damage in the CIR pavement layer also did not significantly affect the predicted distress with low traffic volume. In summary, the implementation of CIR technology in the project improved low-temperature cracking and fatigue performance in the asphalt pavement. Meanwhile, the moisture damage of the CIR asphalt mixture accelerated high-temperature rutting and low-temperature cracking, but it may be acceptable when used for low-volume roads

Research progress of integrated stress response in pathogenesis of Alzheimer's disease

Integrated stress response (ISR) is a cellular adaptive response induced by stress, which is strictly regulated by multiple phosphokinases, phosphatases and other proteins to maintain protein homeostasis. Studies have shown that ISR is abnormally activated in Alzheimer's disease, and targeted regulation of different proteins in ISR pathway inhibits the abnormal activation of ISR, leading to restoration of protein homeostasis and alleviation of the neuropathological changes and memory impairment in Alzheimer's disease models. These lines of evidence suggest that ISR has the potential to be a therapeutic target in Alzheimer's disease treatment. This paper reviews the abnormal activation and regulation mechanism of ISR in Alzheimer's disease and discusses the application of ISR as therapeutic targets to Alzheimer's disease models

The effect of hamstring donor-site block for functional outcomes and rehabilitation after anterior cruciate ligament reconstruction

PurposeTo determine the effect of local infiltration anesthesia (LIA) at the donor site combined with a femoral nerve block (FNB) on short-term postoperative pain, functional outcomes, and rehabilitation after arthroscopic hamstring tendon autograft anterior cruciate ligament reconstruction (ACLR).MethodsThis study was a single center, randomized controlled trial. Seventy-three subjects with ACL rupture were enrolled. Participants were randomly allocated to two groups, 47 in the experimental group (Group A) and 26 in the control group (Group B). All operations were performed under FNB. In Group A, 10 ml of 1% ropivacaine was injected precisely at the hamstring donor site. Patients in Group B were treated with the same amount of saline. Preoperatively and postoperatively, pain scores based on the numerical rating scale (NRS) and consumption of opioids were recorded. In addition, knee functions were assessed by the International Knee Documentation Committee Subjective Knee Form (IKDC), the Lysholm score, and the Knee injury and Osteoarthritis Outcome Score (KOOS) preoperatively and postoperatively at 1 and 3 months. In addition, we applied the KNEELAX3 arthrometer to evaluate the stability of the knee preoperatively and postoperatively so that subjective and objective knee conditions were obtained to help us assess knee recovery in a comprehensive manner.ResultsThe hamstring donor-site block reduced pain within the first 12 postoperative hours. There were no significant differences between two groups in pain intensity preoperatively and equal to or greater than 24 hours postoperatively. Furthermore, there were no differences between the groups concerning knee functions preoperatively or in the short-term follow-up at 1 and 3 months.ConclusionLIA at the donor site can effectively improve the early postoperative pain of patients after ACLR and reduce the use of opioids without affecting the functional outcomes of the surgery

Leakage Flow Characteristics in Blade Tip of Shaft Tubular Pump

The shaft tubular pump device is widely used in various water diversion projects because of its ultra-low head and large flow characteristics. Due to the tip clearance between the blade and the shroud, it is easy to cause hydraulic mechanical performance changes, induced vibration, and noise, which seriously affects the safe and stable operation of the pump. Steady and unsteady three-dimensional flow field numerical simulations of a shaft tubular pump device were carried out using computational fluid dynamics to investigate the impeller flow properties of the device under various flow conditions, including the tip clearance leakage flow (TCLF) and change rule of pressure pulsation. The TCLF, vortex morphology evolution, and pressure pulsation properties of the impeller tip clearance were analyzed. The results show that with an increase in the flow rate, the influence of the tip clearance size on the tip clearance flow decreases, the TCLF decreases, and the axial velocity of the water flow at the tip clearance increases. When the flow rate increases, the swirling strength of the tip leakage vortex decreases, and the distance between the tip leakage vortex and the suction surface of the blade increases. With the increase in flow rate, the pressure pulsation amplitude at the tip clearance increases first and then decreases. The focus of this study is to analyze the variation of tip clearance flow field and pressure pulsation under multiple working conditions, aiming to provide some help for improving the performance of the pump device and ensuring its safe operation

Pyroptosis and Sarcopenia: Frontier Perspective of Disease Mechanism

With global ageing, sarcopenia, as an age-related disease, has brought a heavy burden to individuals and society. Increasing attention has been given to further exploring the morbidity mechanism and intervention measures for sarcopenia. Pyroptosis, also known as cellular inflammatory necrosis, is a kind of regulated cell death that plays a role in the ageing progress at the cellular level. It is closely related to age-related diseases such as cardiovascular diseases, Alzheimer’s disease, osteoarthritis, and sarcopenia. In the process of ageing, aggravated oxidative stress and poor skeletal muscle perfusion in ageing muscle tissues can activate the nod-like receptor (NLRP) family to trigger pyroptosis. Chronic inflammation is a representative characteristic of ageing. The levels of inflammatory factors such as TNF-α may activate the signaling pathways of pyroptosis by the NF-κB-GSDMD axis, which remains to be further studied. Autophagy is a protective mechanism in maintaining the integrity of intracellular organelles and the survival of cells in adverse conditions. The autophagy of skeletal muscle cells can inhibit the activation of the pyroptosis pathway to some extent. A profound understanding of the mechanism of pyroptosis in sarcopenia may help to identify new therapeutic targets in the future. This review article focuses on the role of pyroptosis in the development and progression of sarcopenia

Research Trends of Patient-Reported Outcome Measures in Orthopedic Medical Practices: A Bibliometric and Visualized Study

Background and Objectives: Patient-reported outcome measures (PROMs), also known as self-report measures, are critical tools for evaluating health outcomes by gathering information directly from patients without external interpretation. There has been a growing trend in the number of publications focusing on PROMs in orthopedic-related research. This study aims to identify the most valuable publications, influential journals, leading researchers, and core countries in this field using bibliometric analysis, providing researchers with an understanding of the current state and future trends of PROMs in orthopedic research. Materials and Methods: All PROMs in orthopedic-related publications from 1991 to 2022 were obtained from the WoSCC database. R software (version 4.2.2), VOSviewer (version 1.6.17), and Microsoft Excel (version 2303) were used for the bibliometric and visual analysis. Results: A total of 2273 publication records were found from 1991 to 2022. The results indicated that the United States (US) has made significant contributions to orthopedic-related PROMs. The majority of active research institutions are located in the US. J ORTHOP RES has published the most articles. J BONE JOINT SURG AM has the highest total citations. Conclusions: Our study provides a valuable reference for further exploration of the application of PROMs in orthopedics. PROMs have emerged as an increasingly popular area of research within the field of orthopedics, both in clinical practice and academic research. We conducted a bibliometric analysis in terms of journals, authors, countries, and institutions in this field. Additionally, we analyzed the potentialities and advantages of using PROMs in orthopedic research. There is an increasing trend towards using network-based or short message service (SMS)-based electronic patient-reported outcome measures (ePROMs) in orthopedic medical practices. It is anticipated that the role of PROMs in psychological and mental health research and telemedicine will continue to grow in importance

Pyroptosis and Sarcopenia: Frontier Perspective of Disease Mechanism

With global ageing, sarcopenia, as an age-related disease, has brought a heavy burden to individuals and society. Increasing attention has been given to further exploring the morbidity mechanism and intervention measures for sarcopenia. Pyroptosis, also known as cellular inflammatory necrosis, is a kind of regulated cell death that plays a role in the ageing progress at the cellular level. It is closely related to age-related diseases such as cardiovascular diseases, Alzheimer’s disease, osteoarthritis, and sarcopenia. In the process of ageing, aggravated oxidative stress and poor skeletal muscle perfusion in ageing muscle tissues can activate the nod-like receptor (NLRP) family to trigger pyroptosis. Chronic inflammation is a representative characteristic of ageing. The levels of inflammatory factors such as TNF-α may activate the signaling pathways of pyroptosis by the NF-κB-GSDMD axis, which remains to be further studied. Autophagy is a protective mechanism in maintaining the integrity of intracellular organelles and the survival of cells in adverse conditions. The autophagy of skeletal muscle cells can inhibit the activation of the pyroptosis pathway to some extent. A profound understanding of the mechanism of pyroptosis in sarcopenia may help to identify new therapeutic targets in the future. This review article focuses on the role of pyroptosis in the development and progression of sarcopenia

Deleting IP6K1 stabilizes neuronal sodium–potassium pumps and suppresses excitability

Abstract Inositol pyrophosphates are key signaling molecules that regulate diverse neurobiological processes. We previously reported that the inositol pyrophosphate 5-InsP7, generated by inositol hexakisphosphate kinase 1 (IP6K1), governs the degradation of Na+/K+-ATPase (NKA) via an autoinhibitory domain of PI3K p85α. NKA is required for maintaining electrochemical gradients for proper neuronal firing. Here we characterized the electrophysiology of IP6K1 knockout (KO) neurons to further expand upon the functions of IP6K1-regulated control of NKA stability. We found that IP6K1 KO neurons have a lower frequency of action potentials and a specific deepening of the afterhyperpolarization phase. Our results demonstrate that deleting IP6K1 suppresses neuronal excitability, which is consistent with hyperpolarization due to an enrichment of NKA. Given that impaired NKA function contributes to the pathophysiology of various neurological diseases, including hyperexcitability in epilepsy, our findings may have therapeutic implications

Waste cathode-ray-tube glass powder modified asphalt materials: Preparation and characterization

Cathode-ray-tube (CRT) is the ingredient of glass used in obsolescent televisions or computer monitors. CRT glass contains a considerable amount of heavy metals, and the landfilling of CRT glass is significantly harmful to the environment. In an effort to recycle waste CRT glass instead of landfilling it, recycled CRT glass powders were introduced to asphalt binders as a modifier in this preliminary investigation. The recycled CRT glass was processed to a particle size smaller than 0.075 mm and mixed with asphalt binder (PG 58–28) to produce asphalt mastics with four different concentrations (0, 5, 10, and 15 wt%). The rheological performance was characterized with the rotational viscosity (RV), dynamic shear rheometer (DSR), and multiple stress creep recovery (MSCR) tests. The fatigue performance was evaluated by linear amplitude sweep (LAS) test. Meanwhile, the low-temperature properties were measured by the asphalt binder cracking device (ABCD). The hazard materials leaching test was applied to evaluate the leaching potential of lead content into the external environment due to the high lead content in the modified asphalt. The test results revealed that the increase of CRT glass powder content improved the energy of activation compared with that of virgin binder, as well as the resistance of permanent deformation. Furthermore, the incorporation of CRT glass powder may slightly increase the fatigue life of asphalt because of the improved physicochemical interaction between glass and bitumen. The low-temperature cracking temperature first decreased with the increase of CRT glass powder content and then increased as the CRT content increased further. The leaching test demonstrated that the CRT glass powders incorporated into asphalt binders represented a lower lead leaching content than that of the original CRT glass powder, where the lead leaching amount of CRT glass modified asphalt binder is obviously lower than the specified level of 5 mg/L. Therefore, it is possibly acceptable to recycle CRT glass powders in asphalt binders as an additive as an environmental-friendly recycling method, in which the optimal addition content of CRT glass powders could be up to 10% (wt.)