Recent literature extensively investigates the crucial role of energy metabolism in determining the inflammatory response and polarization status of macrophages. This rapidly expanding area of research highlights the importance of understanding the link between energy metabolism and macrophage function. The metabolic pathways in macrophages are intricate and interdependent, and they can affect the polarization of macrophages. Previous studies suggested that glucose flux through cytosolic glycolysis is necessary to trigger pro-inflammatory phenotypes of macrophages, and fatty acid oxidation is crucial to support anti-inflammatory responses. However, recent studies demonstrated that this understanding is oversimplified and that the metabolic control of macrophage polarization is highly complex and not fully understood yet. How the metabolic flux through different metabolic pathways (glycolysis, glucose oxidation, fatty acid oxidation, ketone oxidation, and amino acid oxidation) is altered by obesity- and type 2 diabetes (T2D)-associated insulin resistance is also not fully defined. This mini-review focuses on the impact of insulin resistance in obesity and T2D on the metabolic flux through the main metabolic pathways in macrophages, which might be linked to changes in their inflammatory responses. We closely evaluated the experimental studies and methodologies used in the published research and highlighted priority research areas for future investigations.

OBJECTIVE: To determine the effects of conventional cigarette smoking (CS) and recent heated tobacco products (HTPs) on the surface roughness and color stability of different indirect restorative materials.
METHODS: One hundred disc-shaped samples were constructed of three different restorative CAD/CAM materials: lithium disilicate glass-ceramic (IPS e.max CAD; Ivoclar Vivadent, Liechtenstein), zirconia (BruxZir® Zirconia, Glidewell, USA) and polyetheretherketone (BioHPP® bredent GmbH, Germany). Of the IPS e.max CAD and the Bruxzir samples, 20 samples were glazed, and 20 samples were polished, while the BioHPP samples were all polished according to the manufacturer\'s instructions. Fifty samples were subjected to conventional cigarette smoking (LM, Philip Morris International Inc., Egypt) (Groups: IPS e.max CAD_Glazed exposed to CS (LD_G_Cig), IPS e.max CAD_Polished exposed to CS (LD_P_Cig), Bruxzir_Glazed exposed to CS (Zr_G_Cig), Bruxzir _Polished exposed to CS (Zr_P_Cig) and BioHPP exposed to CS (PEEK_Cig) and fifty samples were exposed to heated tobacco product smoking (Heets, Russet selection, Philip Morris International Inc., Italy) (Groups: IPS e.max CAD_Glazed exposed to HTP (LD_G_HTP), IPS e.max CAD_Polished exposed to HTP (LD_P_HTP), Bruxzir_Glazed exposed to HTP (Zr_G_HTP), Bruxzir CAD_Polished exposed to HTP (Zr_P_HTP) and BioHPP exposed to HTP (PEEK_HTP).. Six hundred cigarettes/heets representing 30 days of medium smoking behavior (20 cigarettes/day) were used. Before and after exposure to smoke, the surface roughness of all the samples was measured using JITAI8101 surface roughness tester (Beijing Jitai Tech Detection Device Co., Ltd, China, and the color parameters were assessed using VITA Easyshade Advance 4.01 (VITA shade, VITA made, VITA). The data were analyzed using One-way ANOVA, paired sample t-test and independent sample t-test. The significance level was set at α < 0.05. The surface topography was evaluated by scanning electron microscopy (SEM) and analyzed using energy-dispersive X-ray (EDX) spectroscopy to determine changes in the surface chemical composition.
RESULTS: Both types of smoking caused significant increases in the surface roughness of all the samples. There was a significant difference in color change between CS and HTP for all materials with different surface finish (P < 0.01) and zirconia had the greatest effect on color change (P < 0.001). In contrast, polyetheretherketone (PEEK) \"BioHPP\" had the least effect (P < 0.001).
CONCLUSIONS: Exposure to different types of smoking induce changes in the surface topography and color of different esthetic restorative materials. Compared with HTP, conventional cigarette smoke has a greater effect on the surface roughness and color stability of esthetic restorative materials. The glazed surfaces showed less change in surface topography than did the polished surfaces. Zirconia showed better color stability when compared to polyetheretherketone (PEEK).

BACKGROUND: Preservation of the remaining structures while maintaining an esthetic appearance is a major objective in removable partial prosthodontics. So, the aim of the current study was to compare the stresses induced on the supporting structures by two digitally produced esthetic core materials; Zirconia and Polyetheretherketone when used as an extracoronal attachment in distal extension removable partial dentures using strain gauge analysis.
METHODS: A mandibular Kennedy class II stone cast with the necessary abutments\' preparations was scanned. The mandibular left canine and first premolar teeth were virtually removed. An acrylic mandibular left canine and first premolar teeth were prepared with heavy chamfer finish line and scanned. Virtual superimposition of the acrylic teeth in their corresponding positions was done. Two strain gauge slots were designed: distal to the terminal abutment and in the residual ridge. Two models and two sets of scanned teeth were digitally printed. The printed teeth were then placed in their corresponding sockets in each model and scanned. The attachment design was selected from the software library and milled out of Zirconia in the model ZR and Polyetheretherketone in the model PE. Five removable partial dentures were constructed for each model. The strain gauges were installed in their grooves. A Universal testing machine was used for unilateral load application of 100 N (N). For each removable partial denture, five measurements were made. The data followed normal distribution and were statistically analyzed by using unpaired t test. P value < 0.05 was considered to be statistically significant.
RESULTS: During unilateral loading unpaired t test showed statistically significant difference (p = 0.0001) in the microstrain values recorded distal to the abutment between the models ZR (-1001.6 µε ± 24.56) and PE (-682.6 µε ± 22.18). However, non statistically significant difference (p = 0.3122) was observed in the residual ridge between them; ZR (16.2 µε ± 4.53) and PE (15 µε ± 3.74).
CONCLUSIONS: In removable partial dentures, Polyetheretherketone extracoronal attachment induces less stress on the supporting abutments compared to the zirconia one with no difference in the stresses induced by them on the residual ridge.

OBJECTIVE: To analyze the characteristics of PEEK rods retrieved in vivo, specifically their wear and deformation, biodegradability, histocompatibility, and mechanical properties.
METHODS: Six PEEK rods were retrieved from revision surgeries along with periprosthetic tissue. The retrieved PEEK rods were evaluated for surface damage and internal changes using Micro-CT, while light and electron microscopy were utilized to determine any histological changes in periprosthetic tissues. Patient history was gathered from medical records. Two intact and retrieved PEEK rods were used for fatigue testing analysis by sinusoidal load to the spinal construct.
RESULTS: All implants showed evidence of plastic deformation around the screw-rod interface, while the inner structure of PEEK rods appeared unchanged with no visible voids or cracks. Examining images captured through light and electron microscopy indicated that phagocytosis of macrophages around PEEK rods was less severe in comparison to the screw-rod interface. The results of an energy spectrum analysis suggested that the distribution of tissue elements around PEEK rods did not differ significantly from normal tissue. During fatigue testing, it was found that the retrieved PEEK rods cracked after 1.36 million tests, whereas the intact PEEK rods completed 5 million fatigue tests without any failure.
CONCLUSIONS: PEEK rods demonstrate satisfactory biocompatibility, corrosion resistance, chemical stability, and mechanical properties. Nevertheless, it is observed that the indentation at the junction between the nut and the rod exhibits relatively weak strength, making it susceptible to breakage. As a precautionary measure, it is recommended to secure the nut with a counter wrench, applying the preset torque to prevent overtightening.

BACKGROUND: The research focused on the postoperative effect of using interbody fusion cage in lumbar posterior lamina decompression and interbody fusion with pedicle screw by comparing the postoperative effect of using 3D printing (Ti6Al4V) and PEEK material interbody fusion cage.
METHODS: Ninety-one patients with lumbar degenerative diseases from the Department of Spine Surgery of Tianjin Hospital were included in the study cohort. They were divided into 3D group (n = 39) and PEEK group (n = 52) according to the use of interbody fusion cage. The imaging data of the patients were collected and the postoperative data of the 2 groups were compared to evaluate patients\' health status and the recovery of lumbar structure and function after operation.
RESULTS: Combined with the degree of fusion, the clinical effect of 3D printing titanium alloy interbody fusion cage was comprehensively judged. At the last follow-up, the JOA score, ODI index, VAS, prolo function score, and SF-36 scale of the 2 groups showed that the clinical symptoms were better than those before operation (P < .05). The height of intervertebral disc, the area of intervertebral foramen and the physiological curvature of lumbar vertebrae increased in varying degrees after operation (P < .05). At the last follow-up, the vertebral cage fusion rates were as high as 89.13% and 90.91% in the 3D and PEEK groups, with collapse rates of 6.5% and 4.5%, respectively. There were 10 cases of cage displacement in 3D group and 7 cases of cage displacement in PEEK group. There was no significant difference between the 2 groups (P > .05).
CONCLUSIONS: In conclusion, 3D printed (Ti6Al4V) interbody fusion cage can obtain good clinical effect in the surgical treatment of lumbar degenerative diseases. Posterior lumbar lamina decompression, bilateral pedicle screw fixation combined with 3D printed cage interbody fusion is excellent in rebuilding the stability of lumbar vertebrae. 3D printed interbody fusion cage can be an ideal substitute material for intervertebral bone grafting. The stable fusion time of interbody fusion cage after lumbar fusion is mostly from 3 months to half a year after operation.

Eribulin (ERI), clinically utilized for locally advanced or metastatic breast tumors, has shown potential links to the immune system. Notably, the cGAS-STING pathway, a key component of innate immunity, has gained prominence. Yet, limited reports explore ERI\'s effects on the cGAS-STING pathway. Additionally, the nuclear presence of cGAS remains poorly understood. This study uniquely delves into ERI\'s impact on both the cytosolic cGAS-STING pathway and nuclear cGAS. ERI enhances nuclear localization of cGAS, resulting in hyper-activation of the cGAS-STING pathway in triple-negative breast cancer cells. Reduction of cGAS heightened both cell proliferation and ERI sensitivity. In clinical data using ERI in a neo-adjuvant setting, patients with low cGAS cases exhibited reduced likelihood of achieving pathological complete response after ERI treatment. These findings illuminate the potential of cGAS and IFNβ as predictive biomarkers for ERI sensitivity, providing valuable insights for personalized breast cancer treatment strategies.

We describe a versatile and tuneable thiol responsive linker system using thiovinylketones, which relies on the conjugate addition-elimination mechanism of Michael acceptors for the traceless release of therapeutics. In a proof-of-principle study, we translate our findings to exhibit potent thiol-cleavable antibiotic prodrugs and antibody-drug conjugates.

Natural and synthetic polymeric materials, particularly soft and hard tissue replacements, are paramount in medicine. We prepared calcium-incorporated sulfonated polyether-ether ketone (SPEEK) polymer membranes for bone applications. The bioactivity was higher after 21 days of immersion in simulated body fluid (SBF) due to calcium concentration in the membrane. We present a new biomaterial healing system composed of calcium and sulfonated polyether ether ketone (Ca-SPEEK) that can function as a successful biomaterial without causing inflammation when tested on bone marrow cells. The Ca-SPEEK exhibited 13 ± 0.5% clot with low fibrin mesh formation compared to 21 ± 0.5% in SPEEK. In addition, the Ca-SPEEK showed higher protein adsorption than SPEEK membranes. As an inflammatory response, IL-1 and TNF-α in the case of Ca-SPEEK were lower than those for SPEEK. We found an early regulation of IL-10 in the case of Ca-SPEEK at 6 h, which may be attributed to the down-regulation of the inflammatory markers IL-1 and TNF-α. These results evidence the innovative bioactivity of Ca-SPEEK with low inflammatory response, opening venues for bone applications.

BACKGROUND: Whether polyetheretherketone (PEEK) rods have potential as an alternative to titanium alloy (Ti) rods in transforaminal lumbar interbody fusion (TLIF) remains unclear, especially in cases with insufficient anterior support due to the absence of a cage. The purpose of this study was to investigate biomechanical differences between PEEK rods and Ti rods in TLIF with and without a cage.
METHODS: An intact L1-L5 lumbar finite element model was constructed and validated. Accordingly, four TLIF models were developed: (1) Ti rods with a cage; (2) PEEK rods with a cage; (3) Ti rods without a cage; and (4) PEEK rods without a cage. The biomechanical properties were then compared among the four TLIF constructs.
RESULTS: With or without a cage, no obvious differences were found in the effect of PEEK rods and Ti rods on the range of motion, adjacent disc stress, and adjacent facet joint force. Compared to Ti rods, PEEK rods increase the average bone graft strain (270.8-6055.2 µE vs. 319.0-8751.6 µE). Moreover, PEEK rods reduced the stresses on the screw-rod system (23.1-96.0 MPa vs. 7.2-48.4 MPa) but increased the stresses on the cage (4.6-35.2 MPa vs. 5.6-40.9 MPa) and endplates (5.7-32.5 MPa vs. 6.6-37.6 MPa).
CONCLUSIONS: Regardless of whether a cage was used for TLIF, PEEK rods theoretically have the potential to serve as an alternative to Ti rods because they may provide certain stability, increase the bone graft strain, and reduce the posterior instrumentation stress, which might promote bony fusion and decrease instrumentation failure.

Polyetheretherketone (PEEK) is considered as an excellent biomaterial for bone grafting and connective tissue replacement. The clinical potential is, however, limited by its bioinertness, poor osteoconduction, and weak antibacterial activity. These disadvantages can be overcome by introducing suitable additives to produce mineral-polymer composites or coatings. In this work, a PEEK-based bioactive composite has been obtained by blending the polymer with magnesium phosphate (Mg3(PO4)2) particles in amounts ranging from 1 to 10 wt.% using the hot press technique. The obtained composite exhibited improved mechanical and physical properties, above the lower limits set for bone engineering applications. The tested grafts were found to not induce cytotoxicity. The presence of magnesium phosphate induced the mineralisation process with no adverse effects on the expression of the marker crucial for osteoblastic differentiation. The most promising results were observed in the grafts containing 1 wt.% of magnesium phosphate embedded within the PEEK matrix. The improved bioactivity of grafts, together with suitable physical-chemical and mechanical properties, indicate this composite as a promising orthopaedic implant material.