Pad Thickness Research Articles

Moxibustion Regulates the Expression of T Cells in Rheumatoid Arthritis Through Tim-3/Gal-9 Signaling Pathway.

To observe the effects of moxibustion on T cells and T cell immunoglobulin and mucin-domain-containing molecule-3/galectin-9 (Tim-3/Gal-9) pathway in rats with rheumatoid arthritis (RA). To further explore the possible anti-inflammatory mechanism of moxibustion in the treatment of RA. Thirty Sprague Dawley rats were randomly divided into three groups, including a control group, an RA model group, and a moxibustion group. An RA model was created through the injection of Freund's complete adjuvant. In the moxibustion group, rats were treated with moxibustion at acupoints of "Shenshu" and "Zusanli." A total of three courses of treatment were conducted. Then the thickness of foot pad was measured, joint pathological changes were observed by hematoxylin-eosin (HE) staining, the proportion of CD4+T and CD8+T in peripheral blood was detected by flow cytometry, the expression levels of Tim-3 and Gal-9 in synovium were detected by polymerase chain reaction (PCR), and the expressions of CD4+T and CD8+T in synovium were detected by immunofluorescence. HE staining showed that the synovial tissue of the control group was smooth and neatly arranged without inflammatory cell infiltration. In the model group, the joint space was narrowed, the synovial tissue had congestion and edema, and a large number of inflammatory cells infiltrated. Compared with the model group, in the moxibustion group, the joint space narrowed with synovium hyperemia and edema, and the level of inflammatory cell infiltration decreased. Flow cytometry showed that compared with the model group, CD4+T expression in the moxibustion group was downregulated, while CD8+T expression was upregulated. PCR results showed that compared with the model group, the expressions of Tim-3 and Gal-9 in the moxibustion group were upregulated. Immunofluorescence results showed that compared with the model group, CD4+T expression in the moxibustion group was decreased, while CD8+T expression was increased. The results demonstrate that moxibustion not only suppressed the expression of CD4+T but also promoted the expression of CD8+T. The anti-inflammatory effect of moxibustion may be related to the regulation of T cell expression through the Tim-3/Gal-9 signaling pathway.

Seismic performance of prefabricated repairable RCS joints with replaceable multi-segment weakened plates

In order to enable the high-efficiency and easy-operation repairment of prefabricated reinforced concrete column-steel beam (RCS) structure after damage, a novel replaceable assembly RCS joint with multi-segment weakened plate (RCS-MWP) is proposed in this research. The design theory, construction, assembly process, replacement of MWP components and repairment after damaged were introduced. This configuration encompasses three sub-specimens: RCS-MWP, RCS-MWP1, and RCS-MWP2, with varying parameters such as pad thickness and number of weakened segments. For RCS-MWP1 and RCS-MWP2, only the energy dissipation components were replaced after the RCS-MWP were tested and damaged. A comparative study was conducted with a traditional RCS joint with a bolt connection (RCS-B). The test results indicated that the damage to the four specimens (RCS-B, RCS-MWP, RCS-MWP1, and RCS-MWP2) was mainly concentrated at the energy dissipation components, while the reinforced concrete (RC) columns and steel beams remained in the elastic stage with minimal damage. By comparing the RCS-MWP, RCS-MWP1, and RCS-MWP2 specimens, it was observed that RCS-MWP and RCS-MWP2 exhibited second-order buckling, which improved the bearing capacity and energy dissipation capacity. The cumulative energy dissipation of specimens with 8 mm pads in the multi-segmental weakened plate assemblies (RCS-MWP1 and RCS-MWP2) increased by 9% and 59.4% compared to RCS-MWP with 3 mm pads, providing enhanced nodal energy dissipation. The average positive and negative bearing capacities of RCS-B were 70.6% higher than those of the RCS-MWP group, which was caused by the low yield stress of multi-segment weakened plates. After eliminating the residual displacement of specimen RCS-MWP, the seismic performance of the RCS-MWP1 and RCS-MWP2 specimens was barely decreased after diagonally replacing the energy dissipation components. This demonstrates the rationality and feasibility of using replaceable MWP components to repair RCS-MWP joints after the earthquake. It should be noted that the residual displacements after unloading resulted in the restoration of the joints more challenging, hence, prestressing to achieve self-centering could be considered as a potential topic for future research. This proves the feasibility of replacing energy-consuming components.

Plantar Fat Pad Thickness And Its Impact On Ankle Biomechanics In Amateur Runners

Plantar Fat Pad Thickness And Its Impact On Ankle Biomechanics In Amateur Runners

On the Use of Pad Mechanical Properties as a Proxy for Conditioning Response

A proliferation of pad materials in recent years, coupled with the increasing complexity of process integration and limited resources available for process development, has highlighted the need for a more in depth understanding of conditioning interactions and better predictive tools for process and consumable design. We have previously noted a range of conditioning response as illustrated in Figure 1. As the figure illustrates, on some materials the surface height distribution imparted by the pad conditioner is shifted to the left relative to the exponential signature of the pad native porosity which is used as a reference. Denoted regime 1, these surfaces are characterized by the prevalence of “eyelid” features which obscure the line-of-sight path to the bottoms of the pores. In regime 2, the surface height distribution is more balanced, with a smooth transition between the exponential porosity signature and the conditioning signature. In regime 3, there is an abrupt disconnect between the exponential porosity signature and the conditioner signature. Such surfaces are characterized by deep gouges.We are investigating pad material tensile properties as a proxy to help understand and predict these conditioning responses. Figure 2 illustrates the range of typical tensile behavior for polymers. While Figure 2 invokes temperature as the variable that drives these behaviors, note that strain rate can also drive tensile behavior across this range with high temperature being analogous to low strain rate and vice versa.Figure 3 and Table 1 summarize some results from our testing of IC1000, VP5000, VP6000, IK4250H and IK4350L. We have determined that grooved pad materials at their nominal dimensions are adequate for testing according to ASTM D638: Standard Test Method for Tensile Properties of Plastics. Typical delivered pad thickness is within the specifications for sample thickness, and as long as the grooves are oriented to be substantially parallel with the strain axis (pulling direction) reproducible results can be obtained. A range of properties spanning at least about 2x is observed in these pads.Figure 4 gives one example of how this information can be directly applied. The figure illustrates a manifestation of the threshold behavior that is typically observed when conditioning with a pad conditioner with uniform tip height, where all the cutting points are controlled within a height range of about 10 µm. As opposed to a conventional conditioning platform, where there is a much wider range of tip heights, the uniform height-controlled conditioner exhibits a threshold behavior where no measurable cutting occurs below a limiting condition down-force (cdf). Figure 4 illustrates the disconnect between a high down-force, accelerated cutting test, using 14 lbs cdf and designed to return the “CR” value for a conditioner, and typical process cdf levels, in the range of 5 lbs cdf. Note that CR values are generally about an order of magnitude higher than comparable polishing tool level pad wear rates. Whereas conventional platforms yield a linear response between CR and tool level pad wear rates, the uniform height design exhibits an offset, such that at low CR levels, low pad wear rates are observed. The position of this threshold is a function of pad type. These data suggest that this threshold can be correlated with the mechanical strength of the pad material, as determined by the tensile test results.We have also explored the effect of strain rate on tensile response. Strain rates in a typical CMP process may be as high as 105 s-1, and as shown in Figure 2, strain rate can have a significant effect on material behavior. Figure 5 illustrates typical results, illustrating the extremes of response for this group of pads, and Figure 6 shows the normalized response of offset yield and tensile strength as a function of strain rate. Of these materials, only IK4350L exhibits a divergent response, and as shown in Figure 7, IK4350L typically exhibits the most abrupt transition between the exponential porosity signature and the conditioner cutting signature, indicating a tendency towards the gross over-conditioning behavior characteristic of regime 3.Over the range of strain rates explored here, all of these materials can be characterized as “rubbery”. This rubbery behavior can be understood in the context of reported property measurements of CMP pads, which indicate distinct glass transitions related to the soft and hard phases of the polyurethane from which the pad is made. This analysis suggests that pad behavior is dominated by the “rubbery plateau” of the soft segment of the polymer, with the glass transition of the hard segment occurring above typical polishing temperatures. Figure 1

The Role of Plain CT in Assessing and Estimating Normal Values of Pericardial Fat Pad Thickness and Their Correlation With Patient's Age, Gender, Body Weight, and Body Mass Index.

Introduction The pericardial fat pad, located anteriorly to the heart between the pericardium and myocardium, has garnered significant interest in cardiovascular research due to its potential role in the pathophysiology of various cardiac conditions. Despite its proximity to the myocardium, it is distinct from the epicardial fat depot found between the myocardium and the visceral layer of the pericardium. Studies have shown that excess pericardial fat is associated with an increased risk of heart failure and other cardiovascular diseases. Non-contrast computed tomography (CT) is a reliable, non-invasive method for assessing pericardial fat pad thickness, offering less radiation exposure compared to other imaging modalities. Establishing standardized measurements for pericardial fat pad thickness is essential, particularly for the South Indian population, which may exhibit unique genetic, dietary, and lifestyle influences on these measurements. Materials and methods A cross-sectional study was conducted on 300 participants from South India, stratified into three age groups: 18-35, 36-50, and 51-70 years, with body weights ranging from 45 kg to 120 kg. Participants were recruited from outpatient departments and community outreach programs, ensuring equal representation from each age group. Non-contrast CT imaging was performed using a Siemens Somatom goTop 128 Slice CT scanner to measure pericardial fat pad thickness and correlate it with age, gender, body weight, and body mass index. Exclusion criteria included diagnosed cardiac or pericardial diseases, prior chest surgery or trauma, pregnancy, and contraindications to CT scans. Ethical approval was obtained, and informed consent was collected from all participants. Data analysis was performed using SPSS software, employing descriptive statistics, ANOVA, t-tests, and Pearson's correlation. Results The study included 300 participants, with an equal gender distribution of 150 males and 150 females. Pericardial fat pad thickness increased with age, averaging 4.2 mm in the 18-35 age group, 5.1 mm in the 36-50 age group, and 6.4 mm in the 51-70 age group. Males exhibited a higher average thickness (5.6 mm) compared to females (5.0 mm). Body weight also showed a positive correlation with pericardial fat pad thickness, with mean values increasing from 4.5 mm in the 45-60 kg range to 6.7 mm in the 106-120 kg range. Statistical analysis confirmed significant differences in pericardial fat pad thickness across age groups, genders, and weight categories, emphasizing the importance of these factors in assessing cardiovascular risk. Conclusion This study provides a benchmark for pericardial fat pad thickness in the Kancheepuram Population of South India, highlighting its correlation with age, gender, body weight, and body mass index. The findings underscore the significance of non-invasive CT imaging in evaluating cardiovascular risk factors. Further research should focus on longitudinal studies and advanced imaging techniques to enhance the diagnostic accuracy and clinical relevance of pericardial fat pad measurements. The established reference values can aid clinicians in identifying individuals at higher risk for cardiovascular diseases, facilitating early intervention and management.

Analysis of Geometric and Material Parameters in the Modal Stability of Wind Turbine Brakes Using the Complex Eigenvalue Method

Wind energy is a sustainable and forward-thinking investment, harnessing the vast power of the wind to generate electricity. Recent decades have seen significant advancements in floating offshore wind turbines (FOWTs), which hold great potential for expanding offshore wind energy infrastructure. While wind power has grown in popularity, it has raised questions about the operations and maintenance of wind turbines, particularly those located in remote and challenging environments. Offshore wind energy offers optimal wind conditions and construction flexibility, but FOWTs face complex marine conditions, including turbulent forces, wind variations, and unpredictable weather events. Emergency Mechanical Braking (EMB) is commonly used to swiftly stop wind turbines during adverse conditions, but frequent use can lead to structural oscillations, mooring failures, and blade damage. These issues can result in emergency situations, increased downtime, and higher maintenance costs. One significant challenge in understanding wind turbine brake system instability is the cost of experimental studies. To address this, our work introduces an iterative method that establishes correlations between brake component properties (like Young’s modulus and friction coefficient), geometric and operational parameters, and key instability factors such as frequency and intensity. Using finite element analysis and complex eigenvalue analysis, this approach focuses on reducing vibration instability and optimizing braking performance. Our study yielded intriguing results, including the observation that reducing brake pad thickness, whether through design choices or natural wear, decreases total unstable points but shifts instabilities to lower frequencies. Ultimately, our research highlights the importance of various parameters in wind turbine brake system instability.

Study on the anti-inflammatory mechanism of moxibustion in rheumatoid arthritis in rats based on phospholipaseA2 signaling inhibition by Annexin 1.

To determine whether moxibustion had an anti-inflammatory effect on rheumatoid arthritis (RA) by regulating Annexin 1 expression and interfering with the phospholipaseA2 signaling pathway. Thirty male Sprague-Dawley rats were randomly categorized into five groups (six rats per group): blank control (CON) group, RA model (RA) group, moxibustion (MOX) group, Annexin 1 lentiviral intervention (RNAi-Anxa1) group, and Annexin 1 lentiviral intervention + moxibustion (RNAi-Anxa1 + MOX) group. The rats in the RNAi-Anxa1 and the RNAi-Anxa1 + MOX groups were injected with the lentiviral vector-mediated RNAi-Anxa1 into the rat foot pad. An experimental RA rat model was established by injecting Freund's complete adjuvant (FCA) into the RA, MOX, RNAi-Anxa1, and RNAi-Anxa1 + MOX groups. Rats in the MOX and RNAi-Anxa1 + MOX groups received moxibustion treatment. After modeling, using moxibustion "Shenshu (BL23)" and "Zusanli (ST36)", each point is 5 times, bilateral alternating, once a day, 6 times for a course of treatment, between the courses of rest for a one day. A total of three treatment courses were conducted. Both bilateral pad thicknesses were measured using Vernier calipers on experimental days 1, 7, 14, 21, and 28. The expression of cPLA2α signaling in the synovium of diseased joints was observed using Western blot. The pathology of the rat ankle synovium was observed using hematoxylin-eosin (HE) staining. Interleukin (IL)-1β, IL-10, prostaglandin E2 (PGE2), and leukotriene B4 (LTB4) were detected using enzyme-linked immunosorbent assay. Moxibustion increased the levels of Annexin 1 and decreased the inflammatory response in rats with RA. After increasing the expression of Annexin 1, the phosphorylated expression of cPLA2α was inhibited, the serum levels of IL-1β, PGE2, and LTB4 decreased, and the level of IL-10 increased. In moxibustion treated RA rats after the Annexin 1 lentiviral intervention, the serum levels of IL-1β, PGE2, LTB4, and IL-10 were almost unchanged. Moxibustion enhanced the negative regulation of the cPLA2α signaling pathway, increased the synovial Annexin 1 expression, inhibited the cPLA2α signaling pathway, indirectly inhibited the expression of downstream inflammatory factors, and played a role in reducing inflammation.

Random Vibration Fatigue Life Prediction of Nano-Silver Solder Joint

Nano-silver is a very potential electronic interconnection material. It’s excellent physical and chemical properties, high thermal conductivity and good electrical conductivity make it very suitable for high power electronic devices. In practical engineering, 20% of the failure of electronic products is caused by vibration load, so it is necessary to study the vibration reliability of interconnected materials. In this paper, the modal and random vibration finite element analysis of nano-silver solder joints were analyzed with workbench software. Predicting random vibration fatigue life of nano-silver solder joint by Coffin-Manson high cycle fatigue empirical formula, Miner’s linear cumulative damage theory and Steinberg model. The random vibration fatigue life of the nanosilver solder joint is 8342 h. It is found that the vibration reliability of nano-silver is inferior to Sn3.0Ag0.5Cu and Sn63Pb37 and the diameter of solder joints and PCB thickness are proportional to the vibration fatigue life, and the PCB thickness has a greater effect on the vibration life than the solder joint diameter. Solder joint height and pad thickness are inversely proportional to vibration fatigue life, and pad thickness has little effect on vibration fatigue life.

Changes in functional characteristics of heel fat pad with age

BackgroundThis study aimed to investigate age-related changes in the heel fat pad's microchamber and macrochamber layers, particularly focusing on load-induced alterations. Understanding these changes is crucial for elucidating age-related differences in foot mechanics and their potential implications for mobility and comfort. MethodsFifty-five healthy individuals were divided into three age groups: young adults (≤29 years), middle-aged adults (30–44 years), and elderly individuals (≥45 years). Ultrasonic imaging was utilized to measure the thickness of the heel fat pad's microchamber and macrochamber layers under varying load conditions. Thickness, percentage changes, and ratios of load-induced thickness changes were calculated to assess age-related differences. FindingsUnder no-load conditions, both microchamber and macrochamber layers of the heel fat pad were significantly thicker in middle-aged and elderly individuals than in young adults. When load was applied middle-aged and elderly participants exhibited smaller changes in the macrochamber layer and larger changes in the microchamber layer compared to young adults. InterpretationOur findings suggest that age influences the structural characteristics and response of the heel fat pad to mechanical loading. Thicker heel fat pad layers in middle-aged and elderly individuals under no-load conditions may reflect age-related changes in fat distribution or composition. Moreover, differences in load-induced thickness changes indicate altered mechanical properties with age, potentially affecting shock absorption and overall foot function. Understanding these age-related variations can help develop interventions aimed at preserving foot health and mobility across the lifespan.

Effect of Pad Thickness and Width Variations on Plastic Limit Moment in Cylindrical Pressure Vessels Due to Nozzle In-Plane Load

This study investigates how different pad thicknesses and diameters affect the maximum stress a cylindrical pressure vessel can handle without failing, particularly around the areas where nozzles are attached. Nozzles on these vessels often face directional stress from loads applied in a specific plane, and these stresses mustn’t push the nozzle material beyond its breaking point. The research used computer simulations to see how these vessels, with various pad sizes and a set shell and nozzle size, behave under increasing stress until they reach their breaking point. Findings indicate that making the pad thicker or wider increases the vessel’s resistance to breaking up to a certain point; beyond this optimal size, making the pad larger doesn’t provide any additional benefit. This information helps design better and safer pressure vessels by identifying the best pad size to prevent failure. The study contributes to understanding how to avoid design issues and optimize the construction of these vessels, adhering to specific industry standards.

Bearing Capacity of a Concrete Grouting Pad on the Working Surface of a Highway Tunnel Shaft

A grouting pad is the key structure for the construction of water inrush grouting on the shaft working surface. Previous methods of calculating the bearing capacity have limitations due to a lack of understanding of the failure mode. To investigate the bearing capacity of a concrete grouting pad on the working surface of a shaft, this paper establishes a mechanical model for the punching shear failure of a grouting pad under symmetrical loading conditions. A unified solution for the bearing capacity is derived, and the influence of parameters is discussed. In addition, a new method for designing the plastic limit thickness is proposed based on this research. The results show that the reason for the grouting pads’ punching shear failure resulted from the formation of peripheral grouting holes “weak ring” caused by the reduction of the bearing capacity. When the thickness of B0 remains constant, the bearing capacity qu of the grouting pad is inversely proportional to the ratio of the diameter and the area of the bottom load. Therefore, following the method of “dividing, interval, and jumping holes” during grouting construction is recommended. The greater the thickness of the grouting pad, the greater the bearing capacity qu will be. When the grouting pad diameter is 2r2 and the thickness B0 is constant, the bearing capacity qu increases with the material tensile strength ft. When designing grouting pads, following the principles of “large thickness, uniform strength theory, high strength materials” will improve bearing performance. The findings have been implemented in the design of the grouting pad thickness for the Tianshan Shengli Tunnel shaft project, which can successfully solve the problem of frequent cracking caused by the weak bearing capacity of a grouting pad. The findings can provide a theoretical basis and reference for the design and construction of grouting pads in a highway tunnel shaft.

Impact of two stage evaporative cooling system using underground water powered by PV panels on improving the thermal comfort of emergency relief tents in dry-hot climate regions

People are often forced to leave their homes owing to several reasons, such as natural disasters and conflicts, and in these cases, speed and cost are critical factors in saving millions of souls. Therefore, relief tents are the best solution in these situations. However, the internal environment of these kinds of tents might be uncomfortable, especially on hot or extremely cold days. Evaporative cooling systems are one of the simple and inexpensive techniques used to improve thermal comfort in a variety of applications, including agricultural, industrial, and residential. For this reason, the present work aims to investigate experimentally the impact of utilizing a two-stage indirect/direct evaporative cooling system using underground water driven by photovoltaic panels on improving the thermal comfort conditions within the relief tent. The experiments were conducted during the summer season of 2022 under different parameters, including the cellulosic pad thickness and the water volume flow rates in direct and indirect cooling stages. The results showed that the used evaporative cooling system improved the thermal comfort conditions inside the tent model, with an indoor daily average temperature reduction of about 12.4–14.8 °C in comparison to the standard tent model. Furthermore, the study outcomes revealed that, due to the remarkable impact of the extra heat exchanger in the indirect cooling stage, the proposed cooling system may offer airflow conditions inside the thermal comfort zone even without utilizing the direct cooling stage.

Comparative analysis of patellar tendon, achilles tendon and plantar fascia structure in indoor and outdoor football players: a novel cross-sectional pilot study

Different sport modalities were associate with tendon adaptation or even tendon disturbances, such as volleyball, soccer or basketball. Purpose: the aim of the present study was to determine de difference between indoor and outdoor football players on patellar tendon (PT), Achilles tendon (AT), plantar fascia (FP) and Hoffa’s fat pad thickness assessed with ultrasound imaging (USI). A cross-sectional study was developed with a total sample of 30 soccer players divided in two groups: outdoor group (n = 15) and indoor group (n = 15). The thickness of PT, AT, PF and Hoffa’s fat pad has been assessed with USI. Hoffa’s fat pad reported significant differences for the left side between groups (P = 0.026). The rest of variables did not show any significant difference (P < 0.05). The ultrasonography assessment of the thickness of the PT, AT and PF did not show differences between outdoor and indoor football players. Hoffa’s fat pad resulted showed a significant decrease for outdoor soccer players with respect futsal players. Thus, it can be considered that the load stimuli received in both soccer players were not enough to produce structural adaptations in PT, AT and PF tissues.

Analysis of Nonweightbearing MRI Fat Pad Thickness Under Central Metatarsals in Patients With and Without Metatarsalgia.

Metatarsalgia is a common diagnosis for patients with forefoot pain. Many have proposed metatarsal fat pad atrophy is a cause of metatarsalgia and therefore have suggested fat grafting instead of distal metatarsal osteotomies to treat metatarsalgia. For fat grafting to be a viable treatment, fat pad atrophy should correlate with metatarsalgia. This study looked to determine the relationship between metatarsal fat pad thickness and metatarsalgia and the correlation between metatarsal fat pad thickness and patient-reported outcomes. We conducted a retrospective review of patients with metatarsalgia and those with foot or ankle osteoarthritis who had a nonweightbearing MRI performed between February 1, 2021, and March 1, 2023. Data collected included demographics, PROMIS scores, metatarsal fat pad thickness in the second and third rays of the affected foot, and thinnest area on coronal section, measured on MRI. Student t test was used to compare continuous variables, whereas the χ2 test was used to compare categorical variables. Multivariable linear regression models were used to control for potential confounding factors. A total of 112 patients were included in this study. Patients with metatarsalgia were significantly more likely to have a lower body mass index (29.3 vs 32.0, P = .03) than patients with osteoarthritis, but this finding was not present when controlling for confounding variables. We found no significant difference in fat pad thickness between patients with metatarsalgia vs patients with foot or ankle osteoarthritis (P = .43). We found no correlation between metatarsal fat pad thickness and pain interference (P = .59), physical function (P = .64), or mobility (P = .94) PROMIS scores. In this retrospective comparative study of a relatively small cohort we found no significant difference in metatarsal fat pad thickness for patients with metatarsalgia vs patients with foot and ankle osteoarthritis based on nonweightbearing MRI, and no association between metatarsal fat pad thickness and patient-reported outcomes. Level III, case control study.

Ultrasound image quality of the carpal tunnel during a pinch grip: effects of coupling media and wrist position

ABSTRACT High quality ultrasound is required for evaluating carpal tunnel dynamics. The purpose of this study was to subjectively assess ultrasound video quality of the carpal tunnel with two commonly used coupling media (coupling gel, 7 mm standoff pad) in two wrist positions (0° neutral, 30° flexion) over the entire time course of a pinch grip. Seventeen participants completed a pinch grip while their carpal tunnel was scanned with ultrasound. The ultrasound videos were graded by two independent reviewers using 10-point scales encompassing median nerve detail, resolution, and total video quality. Intra- and inter-rater reliability were highest for median nerve detail (ICCs>.85). Ultrasound videos in the 0° neutral wrist condition resulted in significantly greater ratings of nerve detail compared to those in 30° wrist flexion. Future studies may benefit from a more customised approach to standoff pad thickness during dedicated analysis of the median nerve in a neutral wrist position.

A novel NLRP3 inhibitor as a therapeutic agent against monosodium urate-induced gout.

Since NEK7 is critical for NLRP3 inflammasome activation, NEK7 inhibitors could be employed as therapeutic agents against gout, a representative disease caused by NLRP3 inflammasome. We designed NEK7 inhibitors based on biochemical kinome profiling of 2,7-substituted thieno[3,2-d]pyrimidine derivatives (SLC3031~3035 and SLC3037). Inflammasome activation was assessed by ELISA of IL-1b and immunoblotting of IL-1b maturation after treatment of bone marrow-derived macrophages with LPS+monosodium urate (MSU). NLPR3 binding to NEK7 and oligomerization were examined using immunoprecipitation and Blue Native gel electrophoresis, respectively. In vivo effect was investigated by studying gross and histopathological changes of food pad tissue of MSU-injected mice, together with assays of maturation of IL-1b and ASC speck in the tissue. SLC3037 inhibited inflammasome by MSU and other inflammasome activators through blockade of NLRP3 binding to NEK7 or oligomerization, and subsequent ASC oligomerization/phosphorylation. SLC3037 significantly reduced foot pad thickness and inflammation by MSU, which was superior to the effects of colchicine. SLC3037 significantly reduced content or maturation of IL-1b and ASC speck in the food pad. The number and height of intestinal villi were decreased by colchicine but not by SLC3037. SLC3037, a NLRP3 inhibitor blocking NEK7 binding to NLRP3, could be a novel agent against diseases associated with NLRP3 inflammasome activation such as gout, cardiovascular diseases, metabolic syndrome or neurodegenerative diseases.

Dimensional changes of Hoffa’s fat pad related to aging: evaluation by MRI

BackgroundHoffa's fat pad is an intra-capsular extra-sinovial structure of the knee joint that has a significant biomechanical and metabolic role, minimizing the influence of stresses created by loading and generating cytokines. Changes in its size can lead to variations in the homeostasis of the knee in elderly patients. This work intends to assess the dimensional variations of Hoffa's fat pad associated to aging in both sexes, using MRI sagittal sequences acquired from the OAI (Osteoarthritis Initiative) database.MethodsWe examined the Hoffa's fat pad sagittal thickness in 217 men and women with knee osteoarthritis who were grouped into four age groups for the study: 40–49; 50–59; 60–69; and 70–80. 3T sagittal IW 2D TSE Fat-suppressed MRI sequences, taken from the OAI (Osteoarthritis Initiative) database, were examined.ResultsHoffa’s fat pad thickness was shown to differ significantly between groups in both men and women, decreasing in the older individuals' groups (R = − 0.46; p 0.0001). By dividing the patients into ten-year age groups and by sex, the thickness of both the right knee and the left knee was examined. In fact, the average thickness of Hoffa's fat pad of the right knee was reported to be, in males, 33.6+/− 3 mm in subjects aged between 40 and 49 years, 31+/− 2.4 mm for patients aged between 50 and 59, 30.3 ± 1.8 mm in the group between 60 and 69 years and 28.7+/− 1.8 mm between 70 and 80 years. In women the values obtained were the following: 29+/− 1.6 mm between 40 and 49 years; 28.9+/− 2.6 mm in the group between 50 and 59 years, 25.3+/− 1.9 mm for patients aged 60 and 69 years and 26+/− 2 mm between 70 and 80 years. Similar results were obtained for the left knee.ConclusionsHoffa’s fat pad gradually thins with aging in both male and female patients with knee osteoarthritis, and this can be detected by evaluating the thickness of the fat pad on sagittal MRI sequences.

Management of Serious Adverse Events Following Deoxycholic Acid Injection for Submental and Jowl Fat Reduction: A Systematic Review and Management Recommendations.

Abstract Pivotal Phase 3 randomized control trials have demonstrated a favorable safety profile for ATX-101 in submental fat (SMF) reduction; however, in real-world settings, several serious adverse events (SAEs) have been reported, most of which are procedure related and avoidable. Current understanding of the management of uncommon AEs and SAEs is based on the aesthetic surgeon's discretion, and overzealous protocols for sclerosis agents are being applied for ATX-101-induced arterial injury. This review focuses on showcasing the management of SAEs reported previously and updating it with personal clinical experiences with ATX-101 for SMF and jowl fat reduction. Along with adherence to the standard procedures for ATX-101 administration, the authors recommend investigating other potential causes of SMF accumulation and jowling mechanism, appropriate demarcation of the surface area to determine the number of vials, and assessment of the fat pad thickness to determine the number of required treatment cycles for optimal therapeutic outcomes. Surgery is preferable for jowling caused by compartment displacement (ptosis), whereas fat-reducing treatments such as ATX-101 are contraindicated for jowling caused by subcutaneous tissue atrophy. Some proactive measures that can be employed to prevent AEs include avoiding intradermal injections to prevent skin ulceration/necrosis, injecting lidocaine to check for smile asymmetry as an indication of marginal mandibular nerve proximity, administering 1 to 2 mm deeper injections in males to prevent alopecia, employing good aseptic techniques to prevent abscess formation, injecting 1 product at a time using correctly labeled syringes, and confirming the diagnosis of pyoderma gangrenosum before treating it as an infection. Level of Evidence: 3

Codonopsis lanceolata polysaccharide ameliorates high-fat diet induced-postpartum hypogalactia via stimulating prolactin receptor-mediated Jak2/Stat5 signaling

This study aims to investigate the ameliorative effect of Codonopsis lanceolata polysaccharide (PCL) on mice with hypogalatia induced by a high-fat diet (HFD) and the potential underlying mechanism. We found that oral administration of PCL demonstrated significant benefits in countering the negative effects of HFD, including weight gain, hepatic steatosis, mesenteric adipocyte hypertrophy, and abnormal glucose/lipid metabolism. In addition, PCL improved mammary gland development and enhanced lactogenesis performance. Histologically, PCL ameliorated the retardation of ductal growth, reduced mammary fat pad thickness, improved the incomplete linear encapsulation of luminal epithelium and myoepithelium, and increased the proliferation of mammary epithelial cells. Flow cytometry analysis showed that PCL mitigated the detrimental effects of HFD on mammary gland development by promoting the proliferation and differentiation of mammary epithelial cells. Mechanistic studies revealed that PCL upregulated the levels of prolactin (PRL) and its receptor (PRLR) in the mammary gland, activated JAK2/STAT5 signaling pathway, and increased the expression of p63, ERBB4, and NRG1. Overall, PCL can ameliorate HFD-induced hypogalactia by activating PRLR-mediated JAK2/STAT5 signaling. Our findings offer a methodological and theoretical foundation for investigating the functional constituents of traditional Chinese medicine in the treatment of hypogalactia.

IoT-Enabled predictive maintenance for sustainable transportation fleets

This study explores the use of Internet of Things (IoT) based predictive maintenance techniques for sustainable transportation fleets. It utilizes various datasets to enhance operational efficiency and reduce environmental consequences. An examination of the fleet data uncovers interesting findings: the average mileage of the fleet is about 28,400 miles, indicating that different vehicles have been used to different extents. Notably, vehicle 002 stands out with the greatest mileage of 32,000 miles. Varying sensor measurements reveal discrepancies in tire pressure, brake pad thickness, and oil levels, suggesting different patterns of wear across the fleet. The historical maintenance data highlight the differences in maintenance intervals among automobiles. Based on predictive maintenance analysis, it is projected that vehicle 001 will need its next oil change after covering 27,000 miles, which is an increase of 2,000 miles compared to its last service. Percentage change study demonstrates the ever-changing nature of maintenance needs, highlighting the need of customized maintenance interventions that are specifically designed for each vehicle's unique characteristics. The combination of these discoveries clarifies the potential of IoT-enabled predictive maintenance in customizing tailored maintenance plans, increasing fleet efficiency, and reducing environmental impact. This research offers practical insights for adopting proactive maintenance techniques, promoting sustainability, and improving operational efficiency in transportation fleets.