Synthesis and cytotoxic evaluation of heterocyclic compounds by vinylic substitution of ketene dithioacetals.

N-heterocyclic compounds are important molecular scaffolds in the search for new drugs, since most drugs contain heterocyclic moieties in their molecular structure, and some of these classes of heterocycles are able to provide ligands for two or more biological targets. Ketene dithioacetals are important building blocks in organic synthesis and are widely used in the synthesis of N-heterocyclic compounds. In this work, we used double vinylic substitution reactions on ketene dithioacetals to synthesize a small library of heterocyclic derivatives and evaluated their cytotoxic activity in breast and ovarian cancer cells, identifying two benzoxazoles with good potency and selectivity. In silico predictions indicate that the two most active derivatives exhibit physicochemical properties within the range of drug-like compounds and showed potential to interact with HDAC8 and ERK1 cancer-related targets.

Rapidly and simply detecting Cr (VI) in aqueous media via a diketopyrrolopyrrole-based chemosensor with both high selectivity and low LOD.

BACKGROUND: The high toxicity of hexavalent chromium [Cr (VI)] could not only cause harmful effects on humans, including carcinogenicity, respiratory issues, genetic damage, and skin irritation, but also contaminate drinking water sources, aquatic ecosystems, and soil, impairing the reproductive capacity, growth, and survival of organisms. Due to these harmful effects, detecting toxic Cr (VI) is of great significance. However, the rapid, simple, and efficient detection at a low Cr (VI) concentration is extremely challenging, especially in an acidic condition (existing as HCrO4-) due to its low adsorption free energy. RESULTS: A diketopyrrolopyrrole-based small molecule (DPPT-PhSMe) is designed and characterized to act as a chemosensor, which allows a high selectivity to Cr (VI) at an acidic condition with a low limit of detection to 10-8 M that is two orders of magnitude lower than the cut of limit (1 µM) recommended by World Health Organization (WHO). Mechanism study indicates that the rich sulfur atoms enhance the affinity to HCrO4-. Combining with favorable features of diketopyrrolopyrrole, DPPT-PhSMe not only allows dual-mode detection (colorimetric and spectroscopic) to Cr (VI), but also enables disposable paper-based sensor for naked-eye detection to Cr (VI) from fully aqueous media. The investigation of DPPT-PhSMe chemosensor for the quantification of Cr (VI) in real life samples demonstrates a high reliability and accuracy with an average percentage recovery of 102.1 % ± 4 (n = 3). SIGNIFICANCE: DPPT-PhSMe represents the first diketopyrrolopyrrole-derived chemosensor for efficient detection to toxic Cr (VI), not only providing a targeted solution to the bottleneck of Cr (VI) detection in acidic conditions (existing as HCrO4-) caused by its low adsorption free energy, but also opening a new scenario for simple, selective, and efficient Cr (VI) detection with conjugated dye molecules.

Effect of Different Adhesive Resin and Composite Veneering Materials on Adhesion to Polyetheretherketone.

OBJECTIVE: To evaluate the effect of different adhesives and veneering resins on the shear bond strength (SBS) of polyetheretherketone (PEEK). METHODS: A total of 138 PEEK specimens were randomly divided into 6 groups according to adhesive material application: Control (C, no application), Adhese Universal (A) (Ivoclar Vivadent, Schaan, Liechtenstein), Gluma Bond Universal (G) (Heraeus Kulzer, South Bend, IN, USA), G-PremioBOND (P) (GC Corporation, Tokyo, Japan), Single Bond Universal (S) (3M, Saint Paul, MN, USA) and visio.link (V) (Bredent, Senden, Germany). Each adhesive group was divided into two subgroups according to the type of veneering material: Estenia direct composite (D) and Gradia Plus indirect composite (IN) (both GC Corporation). After the veneering process, the specimens were aged by thermal cycling. Kruskal-Wallis and Mann-Whitney U tests were used for SBS analysis (P < 0.05). RESULTS: The highest SBS results were obtained in the VIN group, followed by the VD, PD, GIN, AIN, AD, SIN, SD, PIN, GD, CIN and CD groups, respectively (P = 0.001). There were no significant differences in terms of the type of veneering composite when the same adhesive was applied (P > 0.05), except for Gluma Bond Universal (P = 0.009). All the adhesives tested showed clinically acceptable SBS results. CONCLUSION: Visio.link offered the highest adhesion to PEEK, whereas the tested universal adhesives may be used as an alternative to visio.link in clinical settings. It was determined that changing the veneer type has no statistical difference when the same adhesive material is used.

Comparative evaluation of bond strength and color stability of polyetheretherketone and zirconia layered with indirect composite before and after thermocycling: An in vitro study.

AIM: This study investigates the interaction of zirconia and polyetheretherketone (PEEK) with indirect composite in fixed dental prostheses. This investigation aimed to assess the shear bond strength (SBS) and color stability of zirconia and PEEK before and after aging, addressing critical concerns in dental restorative applications. SETTINGS AND DESIGN: The current in vitro study used 96 samples, 48 of which were divided into two groups, zirconia and PEEK, before and after thermocycling. A dual-axis chewing simulator was used for thermocycling. SBS was measured using a universal testing machine, and color stability was checked using a reflective spectrophotometer. MATERIALS AND METHODS: Ninety-six samples were categorized into zirconia and PEEK groups, each with subgroups undergoing thermocycling. Samples were prepared using computer-aided design/computer-aided manufacturing milling and veneered with composite resin. Thermocycling involved 10,000 cycles, simulating stress levels equivalent to approximately 1 year of clinical use. SBS was assessed using standardized tests. Stereomicroscopic analysis was performed to evaluate the type of failure. Color stability of the core materials with indirect composite was done using a spectrophotometer before and after aging. STATISTICAL ANALYSIS USED: Statistical analysis included paired t-tests and independent t-tests in SPSS software. RESULTS: The results revealed that SBS values for composite on PEEK decreased from 13.86 ± 0.164 MPa before thermocycling to 13.46 ± 0.185 MPa after thermocycling, with a significant difference (P < 0.005). However, both pre- and postthermocycling values for PEEK were higher than zirconia. The t-test confirmed the lower bond strength of composite to zirconia, with a noteworthy improvement after aging. Stereomicroscopic images revealed adhesive failure for the zirconia group and mixed (adhesive and cohesive) failure for the PEEK group. ΔE values were 3.21 ± 0.127 and 2.93 ± 0.142 for zirconia and PEEK groups, respectively (P < 0.005). CONCLUSION: Within the limitations of this study, it can be deduced that PEEK is a feasible substitute for zirconia when used in conjunction with indirect composite for the fabrication of dental prostheses.

Comparative evaluation on surface nanohardness, surface microhardness, surface roughness, and wettability of plant-based organic nanoparticle reinforced polyetheretherketone as an implant material - An in vitro study.

AIM: Synthetic inorganic materials are commonly used as reinforcing agents in polyetheretherketone (PEEK) composite, whereas natural organic plant-based reinforcing agents are negligible. Surface hardness, roughness, and wettability are indicative factors of osseointegration behavior to be used as an implant material. This study evaluated micro surface hardness (MSH), nano surface hardness (NSH), surface roughness (SR), and contact angle (CA) of PEEK-Azadirachta indica reinforced at 10 wt%, 20 wt%, and 30 wt%. SETTINGS AND DESIGN: This was an in vitro study. MATERIALS AND METHODS: Neem (A. indica) leaf nanoparticles were prepared and reinforced with PEEK powder at 10%, 20%, and 30% weight ratios by injection molding. Sixty specimens underwent the microhardness and CA testing using a digital microhardness tester, and CA goniometer, respectively, and later nanoindentation test to analyze the nanohardness and SR. STATISTICAL ANALYSIS USED: A one-way ANOVA test with a 95% confidence interval for MSH and NSH, SR, and CA was performed on the samples. A post hoc Bonferroni test was conducted (α = 0.05) to compare the groups. RESULTS: There was a significant increase in nanohardness (P = 0.000) with zero difference in microhardness (P = 0.514). The addition of 10 wt%, 20 wt%, and 30 wt% nanoparticles increased the SR value of the pure PEEK from 273.19 nm to 284.10 (3.99%), 296.91 (8.68%), and 287.54 (5.24%), respectively. In the analysis of the CA, CA 20% shows the lowest angle (63.69) with the highest for control specimens (82.39). There is an increase in the PEEK composite SR with a decrease in CA. CONCLUSIONS: The addition of plant-derived nanoparticles into the PEEK matrix has a significant impact on the hardness and hydrophobicity enhancing cell growth and osteoblastic differentiation during osseointegration of dental implants.

Effect of two esthetic digitally produced materials used in fabrication of extracoronal attachments on the stresses Induced in removable partial dentures.

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 µÎµ ± 24.56) and PE (-682.6 µÎµ ± 22.18). However, non statistically significant difference (p = 0.3122) was observed in the residual ridge between them; ZR (16.2 µÎµ ± 4.53) and PE (15 µÎµ ± 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.

Effect of conventional cigarette smoking and recent heated tobacco products on CAD/CAM restorative materials.

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. MATERIALS AND 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). CONCLUSION: 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).

Experimental Modeling of Cranial Injury and Defect Reconstruction Using Superconstructive Polymers (PEEK).

Experimental model of resection craniotomy with subsequent reconstruction of the defect with a polymer implant enables comprehensive assessment of functional and ultrastructural changes during replacement of the damaged tissue. Reconstruction of a skull defect was accompanied by transient motor disturbance in the acute period and did not cause functional disorders and neurological deficits in a delayed period. Histological examination of osteal and brain tissue revealed no pathological reactions that could be associated with the response to the chemical components of the implant.

Stereoselective Synthesis of meso- and l,l-Diaminopimelic Acids from Enone-Derived α-Amino Acids.

The stereoselective synthesis of meso-diaminopimelic acid (meso-DAP), the key cross-linking amino acid of the peptidoglycan cell wall layer in Gram-negative bacteria, and its biological precursor, l,l-DAP, is described. The key step involved stereoselective reduction of a common enone-derived amino acid by substrate- or reagent-based control. Overman rearrangement of the resulting allylic alcohols, concurrent alkene hydrogenation and trichloroacetamide reduction, and subsequent ruthenium-catalyzed arene oxidation completed the synthesis of each stereoisomer. The synthetic utility of this approach was demonstrated with the efficient preparation of an l,l-DAP-derived dipeptide.

Simultaneously Enhanced Catalytic Activity and Thermostability of a Baeyer-Villiger Monooxygenase from Oceanicola granulosus by Reshaping the Binding Pocket.

Enzymatic oxygenation of various cyclic ketones into lactones via Baeyer-Villiger monooxygenases (BVMOs) could provide a promising route for synthesizing fragrances and pharmaceutical ingredients. However, unsatisfactory catalytic activity and thermostability restricted their applications in the pharmaceutical and food industries. In this study, we successfully improved the catalytic activity and thermostability of a Baeyer-Villiger monooxygenase (OgBVMO) from Oceanicola granulosus by reshaping the binding pocket. As a result, mutant OgBVMO-Re displayed a 1.0- to 6.4-fold increase in the activity toward branched cyclic ketones tested, accompanied by a 3 °C higher melting point, and a 2-fold longer half-life time (t1/2 (45 °C)). Molecular dynamics simulations revealed that reshaping the binding pocket achieved strengthened motion correlation between amino acid residues, appropriate size of the substrate-binding pocket, beneficial surface characteristics, lower energy barriers, and shorter nucleophilic distance. This study well demonstrated the trade-off between the enzyme activity and thermostability by reshaping the substrate-binding pocket, paving the way for further engineering other enzymes.

Efficient Chemical Synthesis of Multi-Monoubiquitylated and Diubiquitylated Histones by the α-Halogen Ketone-Mediated Strategy.

The chemical synthesis of homogeneously ubiquitylated histones is a powerful approach to decipher histone ubiquitylation-dependent epigenetic regulation. Among the various methods, α-halogen ketone-mediated conjugation chemistry has recently been an attractive strategy to generate single-monoubiquitylated histones for biochemical and structural studies. Herein, we report the use of this strategy to prepare not only dual- and even triple-monoubiquitylated histones but also diubiquitin-modified histones. We were surprised to find that the synthetic efficiencies of multi-monoubiquitylated histones were comparable to those of single-monoubiquitylated ones, suggesting that this strategy is highly tolerant to the number of ubiquitin monomers installed onto histones. The facile generation of a series of single-, dual-, and triple-monoubiquitylated H3 proteins enabled us to evaluate the influence of ubiquitylation patterns on the binding of DNA methyltransferase 1 (DNMT1) to nucleosomes. Our study highlights the potential of site-specific conjugation chemistry to generate chemically defined histones for epigenetic studies.

Therapeutic Efficacy, Safety and Predictive Indicators of Eribulin Plus Anti-Angiogenic Medicine for Metastatic Breast Cancer.

OBJECTIVE: To evaluate the efficacy and safety of eribulin plus anti-angiogenic medicine in metastatic breast cancer (MBC), and explore the potential biomarkers. STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Medical Oncology, Xi'an International Medical Centre Hospital, Xi'an, China, from May 2022 to 2023. METHODOLOGY: A total of 40 MBC patients treated with eribulin were enrolled. Patients were divided into two groups based on whether they received eribulin monotherapy or combined therapy. Median progression-free survival (mPFS), the time from the start of erbium treatment to the time of disease progression, was calculated using the Kaplan-Meier method. RESULTS: The eribulin plus anti-angiogenic medicine treatment group had a significantly prolonged mPFS compared to the group without anti-angiogenic medicine treatment (7.0 months vs. 2.0 months, p <0.001). The multivariate analysis identified that the combination of anti-angiogenic therapy (HR = 0.043, p = 0.004) and the occurrence of grade 3-4 neutropenia after the treatment were two predictive factors for longer PFS (HR = 0.322, p = 0.009). In contrast, prior resistance to taxane was predictive of shorter PFS (HR = 4.583, p = 0.019). Other clinic-pathological factors were not significantly associated with PFS. Fisher's exact test showed no significant increase in treatment-related adverse events (all grades) after combination with anti-angiogenic medicine. CONCLUSION: The eribulin plus anti-angiogenic combination may act as a potential therapy for late-line MBC patients with clinically beneficial therapeutic effects. KEY WORDS: Metastatic breast cancer, Eribulin, Anti-angiogenic therapy, Predictive indicators of efficacy.

Tuneable thiol exchange linkers for traceless drug release applications in prodrugs and ADCs.

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.

[Research Progress of 3D-Printed Polyetheretherketone in Implantable Medical Devices].

Polyetheretherketone (PEEK) has emerged as a thermoplastic material of choice in the realm of implantable medical devices, owing to its high biocompatibility and exceptional mechanical strength. Despite its promise for custom-made medical devices, 3D-printed PEEK in orthopedics, trauma, and spinal implants has not yet achieved widespread application. This study outlines the properties of PEEK, 3D-printed PEEK-based composites, and their utilization in implantable medical devices, thereby fostering the development and regulation of next-generation medical devices.

[Development and Challenges of Additive Manufactured Customized Implant].

Additive manufacturing (3D printing) technology aligns with the direction of precision and customization in future medicine, presenting a significant opportunity for innovative development in high-end medical devices. Currently, research and industrialization of 3D printed medical devices mainly focus on nondegradable implants and degradable implants. Primary areas including metallic orthopaedic implants, polyether-ether-ketone (PEEK) bone implants, and biodegradable implants have been developed for clinical and industrial application. Recent research achievements in these areas are reviewed, with a discussion on the additive manufacturing technologies and applications for customized implants. Challenges faced by different types of implants are analyzed from technological, application, and regulatory perspectives. Furthermore, prospects and suggestions for future development are outlined.

Bioactivity, hemocompatibility, and inflammatory response of calcium incorporated sulfonated polyether ether ketone on mouse-derived bone marrow cells.

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.

Engineering the physical properties and photocatalytic activities of a ß-ketoenamine COF using continuous flow synthesis.

Covalent Organic Frameworks (COF) having conjugated backbone are an interesting class of metal-free, visible light active, heterogeneous photocatalysts. Interestingly, synthesis of COF using continuous flow process has emerged as an efficient, alternative method when compared to the traditional batch process. Here, we demonstrate the possibility to engineer the physical properties and hence the adsorption and catalytic activities of a ß-ketoenamine COF by varying monomer flow rate and microreactor design during the continuous flow synthesis. Crystallinity of the COF increases on varying the monomer flow rate from 100 (S-100) to 500 (S-500) and up to 1000 µLmin-1 (S-1000), in an S-shaped microreactor, resulting in an enhanced surface area: 525, 722 and 1119 m2g-1 respectively. The photophysical properties of the COF are also found to vary significantly with the change in flow synthesis conditions. S-1000 is characterized by the highest adsorption of MB, due to its high surface area and accessible pores. On the other hand, S-500 shows the highest photocurrent, a low recombination of photogenerated charges and the lowest charge transfer resistance. Thus, S-500 is found to be the best photocatalyst for the removal of a model pollutant (methylene blue, MB). Further, enhanced photocatalytic removal of MB using S-500 could be achieved by performing the photocatalysis in continuous flow.

The postoperative clinical effects of utilizing 3D printed (Ti6Al4V) interbody fusion cages in posterior lumbar fusion: A retrospective cohort study.

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 induces micronuclei and enhances the nuclear localization of cGAS in triple-negative breast cancer cells.

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 IFNß as predictive biomarkers for ERI sensitivity, providing valuable insights for personalized breast cancer treatment strategies.