Circadian rhythms and breast cancer: from molecular level to therapeutic advancements.

BACKGROUND AND OBJECTIVES: Circadian rhythms, the endogenous biological clocks that govern physiological processes, have emerged as pivotal regulators in the development and progression of breast cancer. This comprehensive review delves into the intricate interplay between circadian disruption and breast tumorigenesis from multifaceted perspectives, encompassing biological rhythms, circadian gene regulation, tumor microenvironment dynamics, and genetic polymorphisms. METHODS AND RESULTS: Epidemiological evidence underscores the profound impact of external factors, such as night shift work, jet lag, dietary patterns, and exercise routines, on breast cancer risk and progression through the perturbation of circadian homeostasis. The review elucidates the distinct roles of key circadian genes, including CLOCK, BMAL1, PER, and CRY, in breast cancer biology, highlighting their therapeutic potential as molecular targets. Additionally, it investigates how circadian rhythm dysregulation shapes the tumor microenvironment, fostering epithelial-mesenchymal transition, chronic inflammation, and immunosuppression, thereby promoting tumor progression and metastasis. Furthermore, the review sheds light on the association between circadian gene polymorphisms and breast cancer susceptibility, paving the way for personalized risk assessment and tailored treatment strategies. CONCLUSIONS: Importantly, it explores innovative therapeutic modalities that harness circadian rhythms, including chronotherapy, melatonin administration, and traditional Chinese medicine interventions. Overall, this comprehensive review emphasizes the critical role of circadian rhythms in the pathogenesis of breast cancer and highlights the promising prospects for the development of circadian rhythm-based interventions to enhance treatment efficacy and improve patient outcomes.

Glucosamine inhibits myoblast proliferation and differentiation, and stimulates myotube atrophy through distinct signal pathways.

Glucosamine (GlcN) is one of the dietary supplements used in the treatment of osteoarthritis. Endogenously, GlcN is synthesized from glucose through the hexosamine pathway. In addition to ameliorating arthritis, several biological functions of GlcN have been reported, including insulin resistance in skeletal muscle. However, the regulatory role of GlcN in skeletal muscle development is not clear. We therefore investigated the effect of GlcN on myoblast proliferation, differentiation, and myotube development and their underlying mechanisms in C2C12 cells. Myoblast proliferation was measured by MTT assay. The expressions of MyoD, myogenin (MyoG), and myosin heavy chain (MyHC) were identified as determinants of myoblast differentiation. Expressions of atrogin-1 and muscle RING-finger protein-1 (MuRF-1) were identified as markers of myotube atrophy. The results show that treatment with GlcN significantly reduced myoblast proliferation and phosphorylation of Stat3 and S6K. These findings suggest that GlcN can inhibit growth of myoblasts through inhibiting phosphorylation of Stat3 and S6K. In addition, GlcN significantly suppressed the expression of MyoD, MyoG, and MyHC, as well as myotube formation. Pretreatment of C2C12 myoblast cells with ER stress inhibitors significantly blocked GlcN-inhibited MyHC expression and myotube formation. It can be concluded that GlcN suppressed myogenic differentiation via a pathway that involved ER stress. Moreover, GlcN decreased myotube diameter and expression of MyHC, as well as increased MuRF-1 in C2C12 myotubes. Meanwhile, GlcN also reduced the expressions of phosphorylated Akt and mTOR were stimulated after GlcN treatment in C2C12 myotubes. Thus, GlcN induced skeletal muscle atrophy by inhibiting the protein synthesis pathway. Chronic GlcN infusion also caused skeletal muscle atrophy in mice. In conclusion, GlcN regulated important stages of skeletal muscle development through different signaling pathways.

Gold as a Promising Electrode Material for LiNbO3-on-Insulator (LNOI) SH-SAW Resonators: An Experimental Study.

The need for wideband radio frequency front ends (RFFEs) with next-generation wireless protocols highlights the importance of electromechanical coupling [Formula: see text]. The hetero acoustic layered (HAL) surface acoustic wave (SAW) resonator with aluminum (Al) electrodes has shown superior performance compared to conventional SAW devices. Despite gold (Au) having excellent conductivity and stable properties, its high acoustic absorption and low phase velocity have made it less favorable for electrodes. This work demonstrates that high-performance shear horizontal (SH)-SAW resonators can be fabricated on the lithium niobate-on-insulator (LNOI) platform using a setup specifically designed for an Au electrodes. Experimental validation shows that the device achieves a high quality factor (Q) over 870, excellent [Formula: see text] up to 40%, and operates around 765 MHz. Unwanted transverse spurious modes are suppressed through adequate electrode design, and the temperature stability of LNOI SH-SAW with Au electrodes is discussed. This study highlights gold's potential as an electrode material for high [Formula: see text], clean spectrum, and wideband applications.

Fixation technique of biodegradable magnesium alloy suture anchor in the rotator cuff repair of the shoulder in a goat model: a technical note.

BACKGROUND: Shoulder disorders, particularly rotator cuff tears, are prevalent musculoskeletal conditions related to aging. Although the widely used suture anchor technique provides strong mechanical support to the tendon, it is associated with a risk of postoperative tendon retearing. The conventionally used titanium alloys can affect the interpretation of magnetic resonance imaging. Degradable magnesium alloys possess excellent biocompatibility, similar mechanical property to the bone, and stimulating bone formation ability from Mg2+. The purpose of this experiment was to develop innovative magnesium-based suture anchors to enhance rotator cuff repair by improving fixation materials, and to evaluate their feasibility in a goat model. METHODS: We developed fluoridized ZK60 suture anchors as the implantation material for two goats, who underwent rotator cuff repair surgery on both shoulders. Computed tomography (CT) and histological analysis were performed at 12 weeks postoperatively, and the results were compared between the magnesium and titanium alloy groups. Additionally, a hematological examination was conducted, which included assessments of red blood cells, white blood cells, platelets, coagulation function, liver function, kidney function, and magnesium ion concentration. RESULTS: The 12-week postoperative CT images showed intact MgF2 ZK60 suture anchors, effectively reconnecting the infraspinatus tendon to the humeral head. The anchors became less visible on CT scans, indicating absorption by surrounding tissues. New bone formation in the MgF2 group surpassed that in the Ti group, demonstrating superior osseointegration. The similarity between cortical bone and magnesium reduced stress-shielding and promoted bone regeneration. Histological analysis revealed successful tendon healing with MgF2 anchors, while the Ti group showed discontinuous interfaces and reduced collagen secretion. Hematological examination showed stable liver, renal function, and magnesium ion levels. CONCLUSIONS: The findings indicate that MgF2-coated suture anchors are feasible for rotator cuff repair and potentially other orthopedic applications. We hope that magnesium alloy anchors can become the solution for rotator cuff tendon repair surgery.

Finite Element Analysis Model for Assessing Expansion Patterns from Surgically Assisted Rapid Palatal Expansion.

Surgically assisted rapid palatal expansion (SARPE) was introduced to release bony resistance to facilitate skeletal expansion in skeletally mature patients. However, asymmetric expansion between the left and right sides has been reported in 7.52% of all SARPE patients, of which 12.90% had to undergo a second surgery for correction. The etiologies leading to asymmetric expansion remain unclear. Finite element analysis has been used to evaluate the stress associated with SARPE in the maxillofacial structures. However, as a collision of the bone at the LeFort I osteotomy sites occurs only after a certain amount of expansion, most of the existing models do not truly represent the force distribution, given that the expansion amount of these existing models rarely exceeds 1 mm. Therefore, there is a need to create a novel finite element model of SARPE that could perform a clinically required amount of expander activation for further analysis of the expansion patterns of the hemimaxillae in all three dimensions. A three-dimensional (3D) skull model from cone beam computed tomography (CBCT) was imported into Mimics and converted into mathematical entities to segment the maxillary complex, maxillary first premolars, and maxillary first molars. These structures were transferred into Geomagic for surface smoothing and cancellous bone and periodontal ligament creation. The right half of the maxillary complex was then retained and mirrored to create a perfectly symmetrical model in SolidWorks. A Haas expander was constructed and banded to the maxillary first premolars and first molars. Finite element analysis of various combinations of buccal osteotomies at different angles with 1 mm clearance was performed in Ansys. A convergence test was conducted until the desired amount of expansion on both sides (at least 6 mm in total) was achieved. This study lays the foundation for evaluating how buccal osteotomy angulation influences the expansion patterns of SARPE.

Influence of Spin Coating and Dip Coating with Gelatin/Hydroxyapatite for Bioresorbable Mg Alloy Orthopedic Implants: In Vitro and In Vivo Studies.

Suitable biomechanical properties, good biocompatibility, and osteoconductivity of a degradable magnesium (Mg) alloy make it a potential material for orthopedic implants. The main limitation of Mg is its high corrosion rate in the human body. Surface modification is necessary to improve the Mg corrosion resistance. In this work, a polymeric layer of gelatin/nanohydroxyapatite (Gel/nHA) was coated on a ZK60 Mg alloy by dip coating and spin coating to test the corrosion resistance and biocompatibility in vitro and in vivo. The results from the in vitro test revealed that the coated groups reduced the corrosion rate with the corrosion current density by 59 and 81%, from 31.22 to 12.83 µA/cm2 and 5.83 µA/cm2 in the spin coating and dip coating groups, respectively. The dip coating group showed better corrosion resistance than the spin coating group with the lowest released hydrogen content (17.5 mL) and lowest pH value (8.23) and reducing the current density by 45%. In vitro, the relative growth rate was over 75% in all groups tested with MG63, demonstrating that the Mg substrate and coating materials were within the safety range. The dip coating and spin coating groups enhanced the cell proliferation with significantly higher OD values (3.3, 3.0, and 2.5, respectively) and had better antihemolysis and antiplatelet adhesion abilities than the uncoated group. The two coating methods showed no difference in the cellular response, cell migration, hemolysis, and platelet adhesion test. In in vivo tests in rats, the dip coating group also showed a higher corrosion resistance with a lower corrosion rate and mass loss than the spin coating group. In addition, the blood biochemistry and histopathology results indicated that all materials used in this study were biocompatible with living subjects. The present research confirmed that the two methods have no noticeable difference in cell and organ response but the corrosion resistance of dip coating was higher than that of spin coating either in vitro or in vivo.

Functional and structural properties of cardiotoxin isomers produced by blocking negatively charged groups.

In this study, we investigated the functional roles of Asp40, Asp57, and C-terminal Asn60 in Naja atra cardiotoxin 3 (CTX3) structure and function by modifying these three carboxyl groups with semicarbazide. The conjugation of the carboxyl groups with semicarbazide produced two conformational isomers whose gross and fine structures were different from those of CTX3. The blocking of the carboxyl groups increased the structural flexibility of CTX3 in response to trifluoroethanol-induced effect. Despite presenting modest to no effect on decreasing the induction of permeability in zwitterionic phospholipid vesicles, the carboxyl group-modified CTX3 showed a marked reduction in its permeabilizing effect on anionic phospholipid vesicles in comparison to that of the native protein. Compared with native CTX3, carboxyl group-modified CTX3 exhibited lower activity in inducing membrane leakage in U937 cells. The CD spectra of lipid-bound toxins and the color transition of polydiacetylene/lipid assay showed that the membrane interaction mode of CTX3 was distinctly changed by the modification in the carboxyl groups. Given that the selective modification of Asp40 does not cause the conformational isomerization of CTX3, our data indicate that the carboxyl groups in Asp57 and Asn60 are essential in maintaining the structural topology of CTX3. Furthermore, modification of carboxyl groups changes the interdependence between the infrastructure and the global conformation of CTX3 in modulating membrane permeabilizing activity.

Status of Asp29 and Asp40 in the Interaction of Naja atra Cardiotoxins with Lipid Bilayers.

It is widely accepted that snake venom cardiotoxins (CTXs) target the plasma membranes of cells. In the present study, we investigated the role of Asp residues in the interaction of Naja atra cardiotoxin 1 (CTX1) and cardiotoxin 3 (CTX3) with phospholipid bilayers using chemical modification. CTX1 contains three Asp residues at positions 29, 40, and 57; CTX3 contains two Asp residues at positions 40 and 57. Compared to Asp29 and Asp40, Asp57 was sparingly modified with semi-carbazide, as revealed by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass and mass/mass analyses. Thus, semi-carbazide-modified CTX1 (SEM-CTX1) mainly contained modified Asp29 and Asp40, while SEM-CTX3 contained modified Asp40. Compared to that of native toxins, trifluoroethanol easily induced structural transition of SEM-CTX1 and SEM-CTX3, suggesting that the structural flexibility of CTXs was constrained by Asp40. Modification of Asp29 and Asp40 markedly promoted the ability of CTX1 to induce permeability of cell membranes and lipid vesicles; CTX3 and SEM-CTX3 showed similar membrane-damaging activity. Modification of Asp residues did not affect the membrane-binding capability of CTXs. Circular dichroism spectra of SEM-CTX3 and CTX3 were similar, while the gross conformation of SEM-CTX1 was distinct from that of CTX1. The interaction of CTX1 with membrane was distinctly changed by Asp modification. Collectively, our data suggest that Asp29 of CTX1 suppresses the optimization of membrane-bound conformation to a fully active state and that the function of Asp40 in the structural constraints of CTX1 and CTX3 is not important for the manifestation of membrane-perturbing activity.

The effects of ultrasonic agitation on supercritical CO2 copper electroplating.

Applying ultrasound to the electroplating process can improve mechanical properties and surface roughness of the coating. Supercritical electroplating process can refine grain to improve the surface roughness and hardness. However, so far there is no research combining the above two processes to explore its effect on the coating. This study aims to use ultrasound (42kHz) in supercritical CO2 (SC-CO2) electroplating process to investigate the effect of ultrasonic powers and supercritical pressures on the properties of copper films. From the results it was clear that higher ultrasonic irradiation resulted in higher current efficiency, grain refinement, higher hardness, better surface roughness and higher internal stress. SEM was also presented to verify the correctness of the measured data. The optimal parameters were set to obtain the deposit at pressure of 2000psi and ultrasonic irradiation of 0.157W/cm3. Compared with SC-CO2 electroplating process, the current efficiency can be increased from 77.57% to 93.4%, the grain size decreases from 24.34nm to 22.45nm, the hardness increases from 92.87Hv to 174.18Hv, and the surface roughness decreases from 0.83µm to 0.28µm. Therefore, this study has successfully integrated advantages of ultrasound and SC-CO2 electroplating, and proved that applied ultrasound to SC-CO2 electroplating process can significantly improve the mechanical properties of the coating.

Who Is Using Outdoor Fitness Equipment and How? The Case of Xihu Park.

Outdoor fitness equipment (OFE) placed in public parks has the potential to encourage physical activity. However, little is known about OFE users and use patterns. This study employed onsite and video observations of OFE usage to describe user characteristics and patterns in Xihu Park. Results indicate that OFE in this park attracted considerable use, particularly in the early morning and late afternoon. During these peak-hour observations, approximately 12 users per hour used the OFE, with the majority being females and seniors. The triple arm stretch and air walker were the most popular stations. However, most OFE users interacted with less than three of the available six OFE stations. Furthermore, users spent an average of less than nine minutes on all OFE stations combined. While OFE equipment was well-used in this urban park, it appears users did not interact with OFE at rates to produce a sufficient bout or level of physical activity during their park visit. Further investigations of OFE are encouraged to determine their health impact.

Perceptual quality-regulable video coding system with region-based rate control scheme.

In this paper, we discuss a region-based perceptual quality-regulable H.264 video encoder system that we developed. The ability to adjust the quality of specific regions of a source video to a predefined level of quality is an essential technique for region-based video applications. We use the structural similarity index as the quality metric for distortion-quantization modeling and develop a bit allocation and rate control scheme for enhancing regional perceptual quality. Exploiting the relationship between the reconstructed macroblock and the best predicted macroblock from mode decision, a novel quantization parameter prediction method is built and used to achieve the target video quality of the processed macroblock. Experimental results show that the system model has only 0.013 quality error in average. Moreover, the proposed region-based rate control system can encode video well under a bitrate constraint with a 0.1% bitrate error in average. For the situation of the low bitrate constraint, the proposed system can encode video with a 0.5% bit error rate in average and enhance the quality of the target regions.