Effect of easy cupping combined with pelvic floor electrical stimulation and Kegel exercise and pelvic floor muscle surface electromyography on symptoms improvement in women with stress urinary incontinence.

This study aimed to evaluate the effectiveness of easy cupping combined with pelvic floor electrical stimulation and Kegel exercises in treating female patients with stress urinary incontinence (SUI). Ninety SUI patients were randomly assigned to two groups: the control group (pelvic floor electrical stimulation + Kegel exercises) and the experimental group (easy cupping + pelvic floor electrical stimulation + Kegel exercises). Outcomes assessed included pelvic floor muscle strength, urinary incontinence, urinary leakage, pelvic floor muscle surface electromyography, adverse effects, and patient satisfaction before and after treatment. Results showed significant improvements in pelvic floor muscle strength, International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICI-Q-SF) scores, and urinary leakage in both groups, with the experimental group showing greater improvements (P < 0.05). The experimental group also had higher pelvic floor muscle potential values and a greater total effective rate (P < 0.05). No significant differences in adverse effects were noted between groups, and patient satisfaction was higher in the experimental group (P < 0.05). In conclusion, the combination of easy cupping with pelvic floor electrical stimulation and Kegel exercises effectively enhances pelvic floor muscle strength, reduces urinary leakage, and improves patient satisfaction in women with stress urinary incontinence.

Cette étude visait à évaluer l'efficacité des ventouses faciles combinées à la stimulation électrique du plancher pelvien et aux exercices de Kegel dans le traitement des patientes souffrant d'incontinence urinaire d'effort (IUE). Quatre-vingt-dix patients SUI ont été répartis au hasard en deux groupes : le groupe témoin (stimulation électrique du plancher pelvien + exercices de Kegel) et le groupe expérimental (ventouses faciles + stimulation électrique du plancher pelvien + exercices de Kegel). Les résultats évalués comprenaient la force musculaire du plancher pelvien, l'incontinence urinaire, les fuites urinaires, l'électromyographie de la surface des muscles du plancher pelvien, les effets indésirables et la satisfaction des patients avant et après le traitement. Les résultats ont montré des améliorations significatives de la force musculaire du plancher pelvien, des scores de la Consultation internationale sur l'incontinence (ICI-Q-SF) et des fuites urinaires dans les deux groupes, le groupe expérimental montrant de plus grandes améliorations (P < 0,05). Le groupe expérimental présentait également des valeurs de potentiel musculaire du plancher pelvien plus élevées et un taux effectif total plus élevé (P < 0,05). Aucune différence significative dans les effets indésirables n'a été notée entre les groupes et la satisfaction des patients était plus élevée dans le groupe expérimental (P < 0,05). En conclusion, la combinaison de ventouses faciles avec la stimulation électrique du plancher pelvien et les exercices de Kegel améliore efficacement la force musculaire du plancher pelvien, réduit les fuites urinaires et améliore la satisfaction des patientes souffrant d'incontinence urinaire d'effort.

Effect of Hypothermia Preventive Nursing on Perioperative Coagulation Function and Stress Response in Elderly Patients Undergoing Total Hip Replacement.

Background: Total hip replacement (THR) is a surgical procedure in which all or part of the hip joint is replaced with an artificial hip joint to rebuild the motor function of the joint. Objective: To explore the impacts of hypothermia preventive nursing on perioperative coagulation function and stress response in elderly patients undergoing THR. Method: A total of 124 elderly patients who underwent THR from February 2020 to February 2023 were included and assigned to the control group (CG) and observation group (OG). Patients in the CG were provided with routine intraoperative nursing, and patients in the OG were given hypothermia preventive nursing. Results: In contrast to the CG, the postoperative temperature in the OG was elevated, and the awakening time and extubation time in the OG were shorter (P < .05). After operation, prothrombin time, thrombin time, fibrinogen along with D-dimer levels in the CG were higher (P < .05), while those in the OG did not change (P > .05). After the operation, epinephrine and norepinephrine levels in both groups were elevated, with levels being lower in OG than CG (P < .05). The occurrence of hypothermia and postoperative chills in the OG was decreased compared to the CG (P < .05). The nursing satisfaction of patients in the OG was higher compared to the CG (P < .05). After nursing, the scores of physical function, social function, material function, and mental health in the OG were higher than GC (P < .05). Conclusion: Hypothermia preventive nursing during operation can effectively maintain the stable coagulation function of patients, reduce the stress response, decrease the occurrence of chills and hypothermia during the operation, and promote the quality of life, especially in elderly patients with THR, which has a specific nursing role for elderly patients undergoing THR, and thus has certain clinical application value.

Revealing chemistry-structure-function relationships in shark vertebrae across length scales.

Shark cartilage presents a complex material composed of collagen, proteoglycans, and bioapatite. In the present study, we explored the link between microstructure, chemical composition, and biomechanical function of shark vertebral cartilage using Polarized Light Microscopy (PLM), Atomic Force Microscopy (AFM), Confocal Raman Microspectroscopy, and Nanoindentation. Our investigation focused on vertebrae from Blacktip and Shortfin Mako sharks. As typical representatives of the orders Carcharhiniformes and Lamniformes, these species differ in preferred habitat, ecological role, and swimming style. We observed structural variations in mineral organization and collagen fiber arrangement using PLM and AFM. In both sharks, the highly calcified corpus calcarea shows a ridged morphology, while a chain-like network is present in the less mineralized intermedialia. Raman spectromicroscopy demonstrates a relative increase of glucosaminocycans (GAGs) with respect to collagen and a decrease in mineral-rich zones, underlining the role of GAGs in modulating bioapatite mineralization. Region-specific testing confirmed that intravertebral variations in mineral content and arrangement result in distinct nanomechanical properties. Local Young's moduli from mineralized regions exceeded bulk values by a factor of 10. Overall, this work provides profound insights into a flexible yet strong biocomposite, which is crucial for the extraordinary speed of cartilaginous fish in the worlds' oceans. STATEMENT OF SIGNIFICANCE: Shark cartilage is a morphologically complex material composed of collagen, sulfated proteoglycans, and calcium phosphate minerals. This study explores the link between microstructure, chemical composition, and biological mechanical function of shark vertebral cartilage at the micro- and nanometer scale in typical Carcharhiniform and Lamniform shark species, which represent different vertebral mineralization morphologies, swimming styles and speeds. By studying the intricacies of shark vertebrae, we hope to lay the foundation for biomimetic composite materials that harness lamellar reinforcement and tailored stiffness gradients, capable of dynamic and localized adjustments during movement.

Harnessing 3D Printing and Electrospinning for Multiscale Hybrid Patches Mimicking the Native Myocardium.

Engineered cardiac tissues show potential for regenerative therapy in ischemic heart disease. Yet, selection of soft biomaterials for scaffold manufacturing is primarily influenced by empirical and compositional factors, raising concerns about arrhythmic risks due to poor electrophysiological integration. Addressing this, we developed multiscale hybrid myocardial patches mimicking native myocardium's structural and biomechanical attributes, utilizing 3D printing and electrospinning techniques. We compared three patch types: pure silicone and silicone-poly(lactic-co-glycolic acid) (PLGA) with random (S-PLGA-R) and aligned (S-PLGA-A) fibers. S-PLGA-A patches with fiber orientation angles of 95-115° are achieved by applying a secondary electrical field using two parallel aluminum enhancers. With bulk and localized moduli of 350-750 and 13-20 kPa resembling the native myocardium, S-PLGA-A patches demonstrate a sarcomere length of 2.1 ± 0.2 µm, ≥50% higher strain motions and diastolic phase, and a 50-70% slower rise of calcium handling compared to the other two patches. This enhanced maturation and improved synchronization phenomena are attributed to efficient force transmission and reduced stress concentration due to mechanical similarity and linear propagation of electrical signals. This study presents a promising strategy for advancing regenerative cardiac therapies by harnessing the capabilities of 3D printing and electrospinning, providing a proof-of-concept for their effectiveness.

Frictional resistance and delamination mechanisms in 2D tungsten diselenide revealed by multi-scale scratch andin-situobservations.

Friction phenomena in two-dimensional (2D) materials are conventionally studied at atomic length scales in a few layers using low-load techniques. However, the advancement of 2D materials for semiconductor and electronic applications requires an understanding of friction and delamination at a few micrometers length scale and hundreds of layers. To bridge this gap, the present study investigates frictional resistance and delamination mechanisms in 2D tungsten diselenide (WSe2) at 10µm length and 100-500 nm depths using an integrated atomic force microscopy (AFM), high-load nanoscratch, andin-situscanning electron microscopic (SEM) observations. AFM revealed a heterogenous distribution of frictional resistance in a single WSe2layer originating from surface ripples, with the mean increasing from 8.7 to 79.1 nN as the imposed force increased from 20 to 80 nN. High-loadin-situnano-scratch tests delineated the role of the individual layers in the mechanism of multi-layer delamination under an SEM. Delamination during scratch consists of stick-slip motion with friction force increasing in each successive slip, manifested as increasing slope of lateral force curves with scratch depth from 10.9 to 13.0 (× 103) Nm-1. Delamination is followed by cyclic fracture of WSe2layers where the puckering effect results in adherence of layers to the nanoscratch probe, increasing the local maximum of lateral force from 89.3 to 205.6µN. This establishment of the interconnectedness between friction in single-layer and delamination at hundreds of layers harbors the potential for utilizing these materials in semiconductor devices with reduced energy losses and enhanced performance.

Quantum Dots on a String: In Situ Observation of Branching and Reinforcement Mechanism of Electrospun Fibers.

Immobilization of quantum dots (QDs) on fiber surfaces has emerged as a robust approach for preserving their functional characteristics while mitigating aggregation and instability issues. Despite the advancement, understanding the impacts of QDs on jet-fiber evolution during electrospinning, QDs-fiber interface, and composites functional behavior remains a knowledge gap. The study adopts a high-speed imaging methodology to capture the immobilization effects on the QDs-fiber matrix. In situ observations reveal irregular triangular branches within the QDs-fiber matrix, exhibiting distinctive rotations within a rapid timeframe of 0.00667 ms. The influence of FeQDs on Taylor cone dynamics and subsequent fiber branching velocities is elucidated. Synthesis phenomena are correlated with QD-fiber's morphology, crystallinity, and functional properties. PAN-FeQDs composite fibers substantially reduced (50-70%) nano-fibrillar length and width while their diameter expanded by 17%. A 30% enhancement in elastic modulus and reduction in adhesion force for PAN-FeQDs fibers is observed. These changes are attributed to chemical and physical intertwining between the FeQDs and the polymer matrix, bolstered by the shifts in the position of C≡N and C═C bonds. This study provides valuable insights into the quantum dot-fiber composites by comprehensively integrating and bridging jet-fiber transformation, fiber structure, nanomechanics, and surface chemistry.

Improving the development of human engineered cardiac tissue by gold nanorods embedded extracellular matrix for long-term viability.

A myocardial infarction (MI), commonly called a heart attack, results in the death of cardiomyocytes (CMs) in the heart. Tissue engineering provides a promising strategy for the treatment of MI, but the maturation of human engineered cardiac tissue (hECT) still requires improvement. Conductive polymers and nanomaterials have been incorporated into the extracellular matrix to enhance the mechanical and electrical coupling between cardiac cells. Here we report a simple approach to incorporate gold nanorods (GNRs) into the fibrin hydrogel to form a GNR-fibrin matrix, which is used as the major component of the extracellular matrix for forming a 3D hECT construct suspended between two flexible posts. The hECTs made with GNR-fibrin hydrogel showed markers of maturation such as higher twitch force, synchronous beating activity, sarcomere maturation and alignment, t-tubule network development, and calcium handling improvement. Most importantly, the GNR-hECTs can survive over 9 months. We envision that the hECT with GNRs holds the potential to restore the functionality of the infarcted heart.

Unfolded protein response signature unveils novel insights into breast cancer prognosis and tumor microenvironment.

BACKGROUND: The critical role of the unfolded protein response (UPR) in tumorigenesis is widely acknowledged, yet the precise molecular mechanisms underlying its contribution to breast cancer (BC) have not been fully elucidated. The present study aimed to comprehensively explore the expression characteristics and prognostic significance of UPR-related genes in breast cancer METHODS: The transcriptome and clinical data of breast cancer were acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, respectively. Differential expression analysis was conducted on UPR-related genes, and the resulting genes were employed for consensus clustering analysis. A breast cancer prognosis risk model was constructed using univariate, least absolute shrinkage and selection operator (LASSO), and multivariable Cox regression analyses. Difference in survival outcomes between groups were analyzed Kaplan-Meier survival analysis, and receiver operating characteristic (ROC) curve was used to assess predictive performance. The relationship between the risk model and clinical-pathological characteristics, immune infiltration, immunotherapy response, and drug sensitivity was assessed. RESULTS: Differential expression analysis identified 10 UPR-related genes that were differentially expressed in breast cancer. Using the expression matrix of these genes, two molecular subtypes of breast cancer were characterized, which displayed significant differences in prognostic and immune infiltration characteristics. Drawing from the gene expression profiles that distinguish between the molecular subtypes, a prognostic risk scoring model comprising eight genes was developed. This model stratified BC patients from both the training and validation cohorts into high-risk and low-risk groups. Patients in the low-risk group had better prognoses, while those with advanced clinical stage and T stage exhibited higher risk scores. The high- and low-risk groups exhibited notable disparities in immune cell infiltration and the expression of multiple immune checkpoint-related genes. Additionally, the low-risk group demonstrated elevated immunophenoscore, Merck18, CD274, and CAF scores compared to the high-risk group, along with a lesser sensitivity to chemotherapy drugs. These results suggest that patients within the low-risk group may potentially benefit more from immunotherapy and chemotherapy interventions. CONCLUSIONS: This study developed a novel UPR-derived risk signature, which could robustly predict the survival outcome, immune microenvironment, and chemotherapy response of patients with breast cancer.

Understanding spatiotemporal mechanical behavior, viscoelasticity, and functions of stem cell-derived cardiomyocytes.

Understanding myocytes' spatiotemporal mechanical behavior and viscoelasticity is a long-standing challenge as it plays a critical role in regulating structural and functional homeostasis. To probe the time-dependent viscoelastic behaviors of cardiomyocytes with cross-linked polymer networks, we measure stem cell-derived cardiomyocyte's (hiPSC-CM) deformation, adhesion, and contractility using atomic force microscopy (AFM) nanoindentation, fluidic micropipette, and digital image correlation (DIC). Our results show a cytoplasm load of 7-14 nN, a de-adhesion force of 0.1-1 nN, and an adhesion force between two hiPSC-CMs of 50-100 nN with an interface energy of 0.45 pJ. Based on the load-displacement curve, we model its dynamic viscoelasticity and discover its intimate associations with physiological properties. Cell detaching and contractile modeling demonstrate cell-cell adhesion and beating related strains manifesting viscoelastic behavior, highlighting viscoelasticity plays the primary role in governing hiPSC-CM spatiotemporal mechanics and functions. Overall, this study provides valuable information about the mechanical properties, adhesion behaviors, and viscoelasticity of single hiPSC-CM, shedding light on mechanical-structure relationships and their dynamic responses to mechanical stimuli and spontaneous contraction.

COVID-19 mortality prediction using ensemble learning and grey wolf optimization.

COVID-19 is now often moderate and self-recovering, but in a significant proportion of individuals, it is severe and deadly. Determining whether individuals are at high risk for serious disease or death is crucial for making appropriate treatment decisions. We propose a computational method to estimate the mortality risk for patients with COVID-19. To develop the model, 4,711 reported cases confirmed as SARS-CoV-2 infections were used for model development. Our computational method was developed using ensemble learning in combination with a genetic algorithm. The best-performing ensemble model achieves an AUCROC (area under the receiver operating characteristic curve) value of 0.7802. The best ensemble model was developed using only 10 features, which means it requires less medical information so that the diagnostic cost may be reduced while the prognostic time may be improved. The results demonstrate the robustness of the used method as well as the efficiency of the combination of machine learning and genetic algorithms in developing the ensemble model.

High throughput screening system for engineered cardiac tissues.

Introduction: Three dimensional engineered cardiac tissues (3D ECTs) have become indispensable as in vitro models to assess drug cardiotoxicity, a leading cause of failure in pharmaceutical development. A current bottleneck is the relatively low throughput of assays that measure spontaneous contractile forces exerted by millimeter-scale ECTs typically recorded through precise optical measurement of deflection of the polymer scaffolds that support them. The required resolution and speed limit the field of view to at most a few ECTs at a time using conventional imaging. Methods: To balance the inherent tradeoff among imaging resolution, field of view and speed, an innovative mosaic imaging system was designed, built, and validated to sense contractile force of 3D ECTs seeded on a 96-well plate. Results: The system performance was validated through real-time, parallel contractile force monitoring for up to 3 weeks. Pilot drug testing was conducted using isoproterenol. Discussion: The described tool increases contractile force sensing throughput to 96 samples per measurement; significantly reduces cost, time and labor needed for preclinical cardiotoxicity assay using 3D ECT. More broadly, our mosaicking approach is a general way to scale up image-based screening in multi-well formats.

Bridging the Gap in Ashby's Map for Soft Material Properties for Tissue Engineering.

Ashby's map's role in rationally selecting materials for optimal performance is well-established in traditional engineering applications. However, there is a major gap in Ashby's maps in selecting materials for tissue engineering, which are very soft with an elastic modulus of less than 100 kPa. To fill the gap, we create an elastic modulus database to effectively connect soft engineering materials with biological tissues such as the cardiac, kidney, liver, intestine, cartilage, and brain. This soft engineering material mechanical property database is created for widely applied agarose hydrogels based on big-data screening and experiments conducted using ultra-low-concentration (0.01-0.5 wt %) hydrogels. Based on that, an experimental and analysis protocol is established for evaluating the elastic modulus of ultra-soft engineering materials. Overall, we built a mechanical bridge connecting soft matter and tissue engineering by fine-tuning the agarose hydrogel concentration. Meanwhile, a soft matter scale (degree of softness) is established to enable the manufacturing of implantable bio-scaffolds for tissue engineering.

Dynamic Control of Contractile Force in Engineered Heart Tissue.

Three-dimensional engineered heart tissues (EHTs) derived from human induced pluripotent stem cells (iPSCs) have become an important resource for both drug toxicity screening and research on heart disease. A key metric of EHT phenotype is the contractile (twitch) force with which the tissue spontaneously beats. It is well-known that cardiac muscle contractility - its ability to do mechanical work - depends on tissue prestrain (preload) and external resistance (afterload). OBJECTIVES: Here, we demonstrate a technique to control afterload while monitoring contractile force exerted by EHTs. METHODS: We developed an apparatus that can regulate EHT boundary conditions using real-time feedback control. The system is comprised of a pair of piezoelectric actuators that can strain the scaffold and a microscope that can measure EHT force and length. Closed loop control allows dynamic regulation of effective EHT boundary stiffness. RESULTS: When controlled to switch instantaneously from auxotonic to isometric boundary conditions, EHT twitch force immediately doubled. Changes in EHT twitch force as a function of effective boundary stiffness were characterized and compared to twitch force in auxotonic conditions. CONCLUSION: EHT contractility can be regulated dynamically through feedback control of effective boundary stiffness. SIGNIFICANCE: The capacity to alter the mechanical boundary conditions of an engineered tissue dynamically offers a new way to probe tissue mechanics. This could be used to mimic afterload changes that occur naturally in disease, or to improve mechanical techniques for EHT maturation.

Revealing nanomechanical deformation at the interface and degradation in all-thin-film inorganic electrochromic devices.

Recently, progress in electrochromic (EC) devices has been made in optimizing electrode and device configurations and performance. However, the ion insertion/de-insertion induced charge transfer (CT) nanomechanical effect has remained unexplored, i.e., repetitive electrode size changes at the nanoscale and stress/strain generated during electrochemical cycling, which is the focus of this work due to its intimate correlation with the elastic and plastic deformation at the interface. Considering the intervalence electrons, excellent electrochemical kinetics, and dramatic color changes, tungsten oxide (WO3) and nickel oxide (NiO) films are configured as the EC cathode and anode materials, respectively, within a full device. Upon extended cycles (>10 000), the void generation and delamination that occurred at the interface account for performance decay. Encouraged by the findings, nanoindentation mechanical tests and electrical kelvin probe force microscopy were employed to investigate the CT induced effects at the interface. There is a dramatic increase of up to 45% in the elastic Young's modulus in colored/charged WO3 at ∼40 mC cm-2. The correlation between CT and synergistic mechanical effect is interpreted by the Lippman equation. Interestingly, despite the charged state (colored; lithiated) with a relatively flat morphology bringing an ∼3.4 times higher electrostatic surface potential, the electrical work function unexpectedly decreases, arising from the dominant effect of the dipole layer potential over the chemical potential. The interatomic cohesive energy and equilibrium distance increase bury the seeds for mechanical deformation in the long run. This work provides fundamental insights into electro-chemo mechanics and interdisciplinary concerted interfacial effects at the nano/atomic level. The dependence of surface potential, stress, work function, and cohesive energy on electrochemical kinetics has been interpreted.

Localized Nanoindentation Paradigm for Revealing Sutured Tissue Interface Mechanics and Integrity.

This study investigates the nanoindentation technique to elucidate the quasi-static and dynamic stress response at the wounded and sutured tissue interface. In vitro modeling and wound healing analysis enable an understanding of sutured tissue interface integrity, modulus, and stability using an artificial abdominal wall model. Sutured tissues with simple interrupted suturing (SIS) demonstrated a 35-40% higher modulus than simple continuous suturing (SCS). High-density suturing with a suture space of 2.5 mm exhibited a 2-fold higher modulus than low-density suturing with a suture space of 5 mm. The elastic modulus of the sutured pad immersed in deionized water was ∼70-95% of the dry condition. The dynamic stress data indicate that long-term body motions-triggered stress instability at the wound interface was affected by suturing style and density. The pivotal factors determining wound healing are quasi-static and dynamic modulus at the sutured interface, which is intimately associated with patient pain, wound complications, healing speed, and blood flow. The proposed method and data are an original approach to addressing wound healing, contributing to patient well-being and identifying, interpreting, and breaking the drawn-out debates in the suturing field.

Membrane Remodeling of Human-Engineered Cardiac Tissue by Chronic Electric Stimulation.

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) show immature features, but these are improved by integration into 3D cardiac constructs. In addition, it has been demonstrated that physical manipulations such as electrical stimulation (ES) are highly effective in improving the maturation of human-engineered cardiac tissue (hECT) derived from hiPSC-CMs. Here, we continuously applied an ES in capacitive coupling configuration, which is below the pacing threshold, to millimeter-sized hECTs for 1-2 weeks. Meanwhile, the structural and functional developments of the hECTs were monitored and measured using an array of assays. Of particular note, a nanoscale imaging technique, scanning ion conductance microscopy (SICM), has been used to directly image membrane remodeling of CMs at different locations on the tissue surface. Periodic crest/valley patterns with a distance close to the sarcomere length appeared on the membrane of CMs near the edge of the tissue after ES, suggesting the enhanced transverse tubulation network. The SICM observation is also supported by the fluorescence images of the transverse tubulation network and α-actinin. Correspondingly, essential cardiac functions such as calcium handling and contraction force generation were improved. Our study provides evidence that chronic subthreshold ES can still improve the structural and functional developments of hECTs.

Direct Observation of Adhesion and Mechanical Behavior of a Single Poly(lactic-co-glycolic acid) (PLGA) Fiber Using an In Situ Technique for Tissue Engineering.

Nanometer- and submicrometer-sized fiber have been used as scaffolds for tissue engineering, because of their fundamental load-bearing properties in synergy with mechano-transduction. This study investigates a single biodegradable poly(lactic-co-glycolic acid) (PLGA) fiber's load-displacement behavior utilizing the nanoindentation technique coupled with a high-resolution in situ imaging system. It is demonstrated that a maximum force of ∼3 µN in the radial direction and displacement of at least 150% of fiber diameter should be applied to acquire the fiber's macroscopic mechanical properties for tissue engineering. The adhesion behavior of a single fiber is captured using a high-resolution camera. The digital image correlation (DIC) technique is adopted to quantify the adhesion force (∼25 µN) between the fiber and the tip. Adhesion force has also been quantified for the fiber after immersing in phosphate-buffered saline (PBS) to mimic the bioenvironment. A 4-fold increase in adhesion force after PBS treatment was observed due to water penetration and hydrolysis on the fiber's surface. A high similarity between mechanical properties of a single fiber and native tissues (elastic modulus of 10-25 kPa) and superior adhesion force (25-107.25 µN) was observed, which is excellent for promoting cell-matrix communication. Overall, this study examines the mechanics of a single fiber using innovative indentation and imaging processing techniques, disclosing its profound and striking roles in tissue engineering.

MDL-800, the SIRT6 Activator, Suppresses Inflammation via the NF-κB Pathway and Promotes Angiogenesis to Accelerate Cutaneous Wound Healing in Mice.

Sirtuin 6 (SIRT6) is an NAD+-dependent deacetylase belonging to the sirtuin family. It has been shown to participate in wound healing and some inflammation-related disorders. However, the effect of MDL-800, a highly efficient and selective SIRT6 activator, on wound healing and inflammation has not been reported. Therefore, this study investigated whether MDL-800 confers anti-inflammatory effects and promotes wound healing and uncovered the molecular mechanisms involved. This was achieved using mouse models of full-thickness wounds. Results showed that MDL-800 significantly downregulated inflammation by attenuating the release of inflammatory mediators and improved collagen deposition and neovascularization of wounds, thereby accelerating cutaneous wound healing. Furthermore, MDL-800 significantly downregulated expression levels of TNF-α and IL-6 in the dorsal skin tissue of mice via the NF-κB pathway. These results demonstrated that MDL-800 exerted anti-inflammatory and prohealing effects, indicating that the SIRT6/NF-κB/IκB signaling pathway may play an important role in wound healing.

Directional dependence on concomitant pressure and volume increases during left ventricular filling.

Myocardial infarction continues to be a leading cause of mortality and morbidity globally. A major challenge post-myocardial infarction is scar tissue growth, which eventually can lead to heart failure. Cardiovascular regenerative strategies to minimize scar tissue growth and promote cardiac tissue formation are currently being actively pursued via the development of cardiac patches. However, the patch must have viscoelastic properties that mimic healthy cardiac tissues to facilitate proper cardiac patch-to-cell communications. To this end, we investigated the tissue microstructure and the stress relaxation properties of the porcine left ventricle (LV) along its long and short axes using a nanoindentation technique. We found significantly higher collagen density along the long axis than the short axis (p < 0.05). We then identified a much more rapid stress relaxation along the porcine LV's short axis compared to its long axis during the diastolic filling timeframe. Therefore, these findings show that concomitant LV pressure and volume increases from blood filling during diastole are directional dependent, with its short axis responsible for increase in LV volume and the long axis responsible for increase in LV pressure. These directional-dependent stress relaxation properties are essential in the design of structurally, bio-mimetic cardiac patches to support cardiac function and regeneration.

The Obesity-Related Metabolic Gene HSD17B8 Protects Against Breast Cancer: High RNA/Protein Expression Means a Better Prognosis.

BACKGROUND The incidence of breast cancer is increasing annually. Obesity and metabolism are considered risk factors for breast cancer. Discovery of obesity- and metabolism-related breast cancer prognostic genes is imminent. MATERIAL AND METHODS We screened metabolism-related genes (MRG) from KEGG and downloaded the obese female dataset GSE151839 from GEO, which screened differentially-expressed genes (DEGs), seen as female obesity-related genes. The intersection of MRGs and DEGs was obesity-related metabolic genes (OMGs), verified by enrichment analysis. After downloading breast cancer data from TCGA, univariate Cox regression and log-rank P analyses were used to screen hub OMGs related to breast cancer prognosis. ROC curve and Kaplan-Meier (KM) plotter, GEPIA, and GENT2 databases were used to verify the hub OMGs at the RNA level. CPTAC and HLA databases were used to verify the hub OMGs at the protein level. RESULTS We screened 33 OMGs. The results of univariate Cox regression and log-rank P analysis showed 3 of 33 OMGs (ABCA1, LPIN1, HSD17B8) were associated with the prognosis of breast cancer patients. After verification with ROC, KM-plotter, and GEPIA, only HSD17B8 was related to breast cancer prognosis (overall/disease-free survival). Results of GENT2 showed the RNA expression of HSD17B8 in breast cancer subtypes with poor prognosis is significantly lower than that with good prognosis. Results of CPTAC and HLA databases showed that the protein expression level of HSD17B8 in breast cancer tissues was significantly lower than that in adjacent normal tissues. CONCLUSIONS HSD17B8 is a protective gene against breast cancer. The higher the expression of HSD17B8, the better the prognosis of breast cancer patients.