TMCO1 regulates cell proliferation, metastasis and EMT signaling through CALR, promoting ovarian cancer progression and cisplatin resistance.

This study aimed to explore the involvement of Transmembrane and coiled-coil domains 1 (TMCO1) in ovarian cancer progression and its regulatory mechanisms in cisplatin resistance. Using the GEPIA database, we analyzed TMCO1 expression in ovarian cancer and normal tissues. In a cohort of 99 ovarian cancer patients, immunohistochemistry and immunofluorescence were employed to assess TMCO1 expression in tumor and adjacent tissues, correlating findings with clinical and pathological characteristics. TMCO1 overexpression and knockout cell models were constructed, and their impact on non-cisplatin-resistant (SK-OV-3) and cisplatin-resistant (SK-OV-3-CDDP) ovarian cancer cells was investigated through cloning, wound healing, Fluo 4, and Transwell experiments. Knocking down CALR and VDAC1 was performed to examine their effects on TMCO1, cell proliferation, and malignant markers. Subcutaneous tumor models in nude mice elucidated the in vivo role of TMCO1 in tumor growth. Expression levels of CALR, VDAC1, angiogenesis indicators (CD34), and epithelial-mesenchymal transition (EMT) markers were evaluated. TMCO1 expression in ovarian cancer tissue significantly differed from normal tissue, correlating with survival rates. TMCO1 overexpression was associated with lymph node metastases, late FIGO stage, and larger tumors. TMCO1 promoted proliferation, calcium ion elevation, cytoskeletal remodeling, and metastasis in SK-OV-3 and SK-OV-3-CDDP cells, upregulating VDAC1, CALR, Vimentin, N-cadherin, ß-catenin, and downregulating E-cadherin. Silencing TMCO1 inhibited cell growth, proliferation, and angiogenesis in vivo, suppressing the expression of CALR, VDAC1, Vimentin, N-cadherin, and ß-catenin. Overall, this study highlighted TMCO1 as a crucial regulator in ovarian cancer progression, influencing VDAC1 through CALR and impacting diverse cellular processes, offering potential as a targeted therapeutic strategy for ovarian cancer.

The interaction between particles and vascular endothelium in blood flow.

Particle-based drug delivery systems have shown promising application potential to treat human diseases; however, an incomplete understanding of their interactions with vascular endothelium in blood flow prevents their inclusion into mainstream clinical applications. The flow performance of nano/micro-sized particles in the blood are disturbed by many external/internal factors, including blood constituents, particle properties, and endothelium bioactivities, affecting the fate of particles in vivo and therapeutic effects for diseases. This review highlights how the blood constituents, hemodynamic environment and particle properties influence the interactions and particle activities in vivo. Moreover, we briefly summarized the structure and functions of endothelium and simulated devices for studying particle performance under blood flow conditions. Finally, based on particle-endothelium interactions, we propose future opportunities for novel therapeutic strategies and provide solutions to challenges in particle delivery systems for accelerating their clinical translation. This review helps provoke an increasing in-depth understanding of particle-endothelium interactions and inspires more strategies that may benefit the development of particle medicine.

Clinicopathological analysis of rosette-forming glioneuronal tumors.

BACKGROUND: This study aimed to investigate the clinicopathological characteristics, diagnostic indicators, and critical factors for the differential diagnosis of rosette-forming glioneuronal tumor (RGNT). PATIENTS AND METHODS: This retrospective study included six surgically treated RGNT cases. We analyzed and summarized their clinical manifestations, radiological features, histological morphology, immunophenotype, and molecular genetic changes, supplemented with a literature review. RESULTS: The patients comprised four males and two females with a mean age of 35 years. The tumors were located in the cerebellum (two cases); the fourth ventricle, quadrigeminal cistern, and third ventricle (one case each); and the fourth ventricle and brainstem (one case). Clinical manifestations included headaches in four cases, left eyelid ptosis in one case, and one asymptomatic case only identified during physical examination. Microscopically, the tumor cells were uniform in size and were marked by rosette-like or pseudorosette-like structures around the neuropil and blood vessels. Immunohistochemistry revealed biphasic patterns. The central neuropil components of the rosette-like structures around the neuropil and the pseudorosette structures of the perivascular regions expressed Syn, while the cells surrounding the rosettes expressed Olig2 and not GFAP. GFAP and S-100 were expressed in the glial components but not in the rosette or pseudorosette regions. The Ki-67 proliferation index was typically low. Molecular genetic analysis showed that the main molecular changes involved FGFR1 mutation accompanied by PIK3R1 mutation. None of the patients received chemoradiotherapy postoperatively. Follow-up durations varied between 4 and 23 months with no recorded recurrence or metastasis. CONCLUSION: RGNT is a comparatively rare mixed glioneuronal tumor that occurs in the midline structures. Its morphology shows certain overlaps with other low-grade neuroepithelial tumors. Identifying the rosettes around the neuropil is critical for morphological diagnosis, and the molecular identification of FGFR1 mutations accompanied by PIK3R1 mutations can facilitate diagnosis.

Efficacy of sensory-based static balance training on the balance ability, aging attitude, and perceived stress of older adults in the community: a randomized controlled trial.

BACKGROUND: This study explores the effect of sensory-based static balance training on the balance ability, aging attitude, and perceived stress of older adults in the community. It provides a practical basis for the in-depth implementation and revision of the community health management model. METHODS: A randomized controlled intervention study was conducted from 2022 to 2023. A total of 72 older adults were recruited and randomly divided into an intervention group (36 individuals) and a control group (36 individuals). Balance ability (measured by the Short Physical Performance Battery and One Leg Stand Test), aging attitudes, and perceived stress were assessed at baseline and at the 12-week and 24-week follow-ups. Repeated-measures ANOVA and generalized estimating equations were used to compare outcome measures. RESULTS: Sensory-based static balance training was beneficial for balance ability and aging attitude among participants in the intervention group. At the end of the intervention, participants in the intervention group showed significant improvements in SPPB scores and OLST scores compared with the control group (FSPPB = 12.347, P = 0.001, Waldχ2OLST = 45.530, P < 0.001), as well as significant differences in aging attitudes (FAAQ = 18.549, P < 0.001). Multiple comparisons at different time points in the intervention group reveal a significant intervention effect (FSPPB = 29.211, Waldχ2OLST = 80.428, FAAQ = 45.981, all P < 0.05). However, the difference in perceived stress before and after the intervention was not significant (FCPSS = 2.876, P = 0.095). CONCLUSIONS: Sensory-based static balance training significantly improved balance ability and aging attitudes among older adults in the community. The effect on perceived stress among older adults in the community was not significant. TRIAL REGISTRATION: Registered in the Chinese Clinic on 04/06/2022. The registration number is ChiCTR2200060541.

Nanotechnology of inhalable vaccines for enhancing mucosal immunity.

Vaccines are the cornerstone of world health. The majority of vaccines are formulated as injectable products, facing the drawbacks of cold chain transportation, needle-stick injuries, and primary systemic immunity. Inhalable vaccines exhibited unique advantages due to their small dose, easy to use, quick effect, and simultaneous induction of mucosal and systemic responses. Facing global pandemics, especially the coronavirus disease 2019 (COVID-19), a majority of inhalable vaccines are in preclinical or clinical trials. A better understanding of advanced delivery technologies of inhalable vaccines may provide new scientific insights for developing inhalable vaccines. In this review article, detailed immune mechanisms involving mucosal, cellular, and humoral immunity were described. The preparation methods of inhalable vaccines were then introduced. Advanced nanotechnologies of inhalable vaccines containing inhalable nucleic acid vaccines, inhalable adenovirus vector vaccines, novel adjuvant-assisted inhalable vaccines, and biomaterials for inhalable vaccine delivery were emphatically discussed. Meanwhile, the latest clinical progress in inhalable vaccines for COVID-19 and tuberculosis was discussed.

A Dose-Dependent Spatiotemporal Response of Angiogenesis Elicited by Zn Biodegradation during the Initial Stage of Bone Regeneration.

Zinc (Zn) plays a crucial role in bone metabolism and imbues biodegradable Zn-based materials with the ability to promote bone regeneration in bone trauma. However, the impact of Zn biodegradation on bone repair, particularly its influence on angiogenesis, remains unexplored. This study reveals that Zn biodegradation induces a consistent dose-dependent spatiotemporal response in angiogenesis,both in vivo and in vitro. In a critical bone defect model, an increase in Zn release intensity from day 3 to 10 post-surgery is observed. By day 10, the CD31-positive area around the Zn implant significantly surpasses that of the Ti implant, indicating enhanced angiogenesis. Furthermore,angiogenesis exhibits a distance-dependent pattern closely mirroring the distribution of Zn signals from the implant. In vitro experiments demonstrate that Zn extraction fosters the proliferation and migration of human umbilical vein endothelial cells and upregulates the key genes associated with tube formation, such as HIF-1α and VEGF-A, peaking at a concentration of 22.5 µM. Additionally, Zn concentrations within the range of 11.25-45 µM promote the polarization of M0-type macrophages toward the M2-type, while inhibiting polarization toward the M1-type. These findings provide essential insights into the biological effects of Zn on bone repair, shedding light on its potential applications.

Muscle-inspired soft robots based on bilateral dielectric elastomer actuators.

Muscle groups perform their functions in the human body via bilateral muscle actuation, which brings bionic inspiration to artificial robot design. Building soft robotic systems with artificial muscles and multiple control dimensions could be an effective means to develop highly controllable soft robots. Here, we report a bilateral actuator with a bilateral deformation function similar to that of a muscle group that can be used for soft robots. To construct this bilateral actuator, a low-cost VHB 4910 dielectric elastomer was selected as the artificial muscle, and polymer films manufactured with specific shapes served as the actuator frame. By end-to-end connecting these bilateral actuators, a gear-shaped 3D soft robot with diverse motion capabilities could be developed, benefiting from adjustable actuation combinations. Lying on the ground with all feet on the ground, a crawling soft robot with dexterous movement along multiple directions was realized. Moreover, the directional steering was instantaneous and efficient. With two feet standing on the ground, it also acted as a rolling soft robot that can achieve bidirectional rolling motion and climbing motion on a 2° slope. Finally, inspired by the orbicularis oris muscle in the mouth, a mouthlike soft robot that could bite and grab objects 5.3 times of its body weight was demonstrated. The bidirectional function of a single actuator and the various combination modes among multiple actuators together allow the soft robots to exhibit diverse functionalities and flexibility, which provides a very valuable reference for the design of highly controllable soft robots.

Clouclip combined with a questionnaire on the influence factors of myopia in children.

Purpose: To evaluate eye use behavior in myopic and non-myopic children objectively using Clouclip M2 device and subjectively using questionnaire and compare the results. The study also aimed to assess the relationships between ocular biometric parameters and refractive status. Methods: Clouclip M2 was used in monitoring eye use behavior and visual environment in children aged 9-11 years. The participants were monitored for 7 days. On the eighth day, data stored in the device were collected, relevant eye examination were conducted and survey questionnaire was administered. The paired sample t-test was used to compare the eye use behavior obtained objectively and subjectively. The relationships between ocular biometric parameters and refractive status were assessed using the Pearson's Correlation analysis. Results: Spherical equivalent refraction was significantly correlated with axial length, axial length to corneal radius, anterior chamber depth, lens thickness, and corneal radius (P < 0.05). The average time per day spent on near work, the maximum time for single near work, and the average near working distance were significantly lower, and the average total time spent on outdoor activities was significantly longer as determined by questionnaire method than that found using Clouclip M2. Logistic regression analysis revealed that prolonged near work, shorter working distance, presence of parental myopia, and lesser outdoor activities were significant risk factors for myopia. Conclusions: The childhood myopia is influenced by eye use behavior, eye use environment, and parental myopia. Results from this study further support that biometric and optical parameters of the eye determine refractive status. Being an objective method, Clouclip M2 provides an independent eye use behavior data which potentially are more reliable than obtained from subjective method. Our study provided a theoretical basis for myopia prevention and control in clinical practice.

miR­137 is a diagnostic tumor­suppressive miRNA that targets SPHK2 to promote M1­type tumor­associated macrophage polarization.

The present study investigated the expression level of microRNA (miR)-137 in glioma tissues and cell lines and explored its potential diagnostic significance as well as its function effects on glioma cells. miR-137 expression level was detected in glioma tissues using in situ hybridization, and in glioma cell lines using reverse transcription-quantitative PCR (RT-qPCR). The diagnostic significance of miR-137 in glioma was assessed using receiver operating characteristic curve analyses. Quantibody® Human Inflammation Array 1 was used to evaluate the impact of ectopic miR-137 expression on release of cytokines in glioma cell lines. IL-13, TNF-α and IFN-γ levels were detected using ELISA. To confirm that sphingosine kinase 2 (SPHK2) is a target of miR-137, RT-qPCR, western blot analysis and dual-luciferase assay were adopted. The results demonstrated that miR-137 expression was downregulated in both glioma tissues and cell lines. Downregulation of miR-137 was significantly associated with high grade gliomas. Additionally, it was found that overexpression of miR-137 reduced IL-13, but promoted TNFα and IFN-γ production. SPHK2 knockdown inhibited IL-13 release, promoted TNF-α and IFN-γ production. SPHK2 was a direct target of miR-137. Collectively, the results of the present study indicated that miR-137 expression plays a tumor-suppressive role in glioma. It is downregulated in glioma and may promote M1-type TAMs polarization, and may be a diagnostic biomarker and potential therapeutic strategy for glioma treatment in the future.

A Combination of Deep-Sea Water and Fucoidan Alleviates T2DM through Modulation of Gut Microbiota and Metabolic Pathways.

Fucoidan and deep-sea water (DSW) are attractive marine resources for treating type 2 diabetes (T2DM). In this study, the regulation and mechanism associated with the co-administration of the two were first studied using T2DM rats, induced by a high fat diet (HFD) and streptozocin (STZ) injection. Results demonstrate that, compared to those with DSW or FPS alone, the orally administered combination of DSW and FPS (CDF), especially the high dose (H-CDF), could preferably inhibit weight loss, decrease levels of fasting blood glucose (FBG) and lipids, and improve hepatopancreatic pathology and the abnormal Akt/GSK-3ß signaling pathway. The fecal metabolomics data show that H-CDF could regulate the abnormal levels of metabolites mainly through the regulation of linoleic acid (LA) metabolism, bile acid (BA) metabolism, and other related pathways. Moreover, H-CDF could adjust the diversity and richness of bacterial flora and enrich bacterial groups, such as Lactobacillaceae and Ruminococcaceae UCG-014. In addition, Spearman correlation analysis illustrated that the interaction between the gut microbiota and BAs plays an essential role in the action of H-CDF. In the ileum, H-CDF was verified to inhibit activation of the farnesoid X receptor (FXR)-fibroblast growth factor 15 (FGF15) pathway, which is regulated by the microbiota-BA-axis. In conclusion, H-CDF enriched Lactobacillaceae and Ruminococcaceae UCG-014, thereby changing BA metabolism, linoleic acid metabolism, and other related pathways, as well as enhancing insulin sensitivity and improving glucose and lipid metabolism.

Natural Exponential and Three-Dimensional Chaotic System.

Existing chaotic system exhibits unpredictability and nonrepeatability in a deterministic nonlinear architecture, presented as a combination of definiteness and stochasticity. However, traditional two-dimensional chaotic systems cannot provide sufficient information in the dynamic motion and usually feature low sensitivity to initial system input, which makes them computationally prohibitive in accurate time series prediction and weak periodic component detection. Here, a natural exponential and three-dimensional chaotic system with higher sensitivity to initial system input conditions showing astonishing extensibility in time series prediction and image processing is proposed. The chaotic performance evaluated theoretically and experimentally by Poincare mapping, bifurcation diagram, phase space reconstruction, Lyapunov exponent, and correlation dimension provides a new perspective of nonlinear physical modeling and validation. The complexity, robustness, and consistency are studied by recursive and entropy analysis and comparison. The method improves the efficiency of time series prediction, nonlinear dynamics-related problem solving and expands the potential scope of multi-dimensional chaotic systems.

Molecularly imprinted polymers based on calcined rape pollen and deep eutectic solvents for efficient sinapic acid extraction from rapeseed meal extract.

Substances that possess hierarchical and interconnected porous features are ideal choices for acting as skeletons to synthesize surface molecularly imprinted polymers (MIPs). In this work, rape pollen, a waste of biological resources, was calcined and a porous mesh material with a high specific surface area was obtained. The cellular material was adopted as a supporting skeleton to synthesize high-performance MIPs (CRPD-MIPs). The CRPD-MIPs presented an ultrathin imprinted layered structure, with an enhanced adsorption capacity for sinapic acid (154 mg g-1) relative to the non-imprinted polymers. The CRPD-MIPs also exhibited good selectivity (IF = 3.24) and a fast kinetic adsorption equilibrium (60 min). This method exhibited a good linear relationship (R2 = 0.9918) from 0.9440 to 29.26 µg mL-1, and the relative recoveries were 87.1-92.3%. The proposed CRPD-MIPs based on hierarchical and interconnected porous calcined rape pollen may be a valid program for the selective extraction of a particular ingredient from complicated actual samples.

Primary intraosseous Rosai-Dorfman disease: An analysis of clinicopathologic characteristics, molecular genetics, and prognostic features.

Background: Rosai-Dorfman disease (RDD) is a rare histiocytic proliferative disorder of uncertain pathogenesis. Most patients present with proliferation in the lymph nodes manifesting as adenopathy; however, RDD may primarily arise in a variety of extranodal sites, including the bone, which is a great challenge in the diagnosis. The clinicopathological characteristics and prognostic features of primary intraosseous RDD have not been well characterized. Methods: We retrospectively analyzed the clinicopathologic and prognostic features of four cases of primary intraosseous RDD during the past 10 years in our hospital, with a review of an additional 62 cases with complete follow-up data from the literature. Results: Primary intraosseous RDD was identified in 0.14% (4/2,800) of total bone biopsies performed at our institution over the study period. According to our retrospective analysis, a total of 18 cases of primary lymph node, skin, or other non-osseous site-based RDD were diagnosed in our hospital. The ages of the 66 total patients ranged from 1.5 to 76 years, with a median age of 25 years. There were 31 male and 35 female patients, with a male-to-female ratio of 0.89:1. Primary intraosseous RDD occurred most often in the bones of the extremities (60.6%, 40/66), with the proximal tibia being the most common location; 39.4% (26/66) of the cases arose in the axial skeleton, predominantly in the vertebra and craniofacial bones. Solitary masses and multiple tumors were present in 84.8% (56/66) and 15.2% (10/66) of the cases, respectively. Pain of the affected area was the most common presenting symptom. Radiographically, the lesions were lytic with well-defined and usually sclerotic margins. Immunohistochemistry showed that large histiocytes from patients with RDD were positive for OCT2, in addition to S100 and CD68. Molecular tests were performed in seven reported cases and four of our cases. All the 11 cases were non-decalcified. PCR results showed that there were no BRAF-V600E, KRAS, or NRAS mutations in primary intraosseous RDD; only one case with both RDD and Langerhans cell histiocytosis showed BRAF-V600E mutation. The survival data showed that 22.7% (15/66) of the patients experienced recurrences or developed RDD at distant sites during the follow-up period (median follow-up, 13 months; range, 1-106 months). The 5-year progression-free survival (PFS) of the patients with primary intraosseous RDD was 57.5%. We found that there was a significant difference in PFS between female and male patients (p = 0.031). However, there was no statistically significant difference in PFS between patients with solitary masses and multiple tumors (p = 0.698). Similarly, no statistically significant differences in PFS were found between the different age groups (p = 0.908) or tumor locations (p = 0.728). Conclusion: Primary intraosseous RDD is an extremely rare disease. The diagnosis of RDD may be quite challenging because of its non-specific clinical presentation and imaging. Immunohistochemistry showed that large histiocytes were positive for OCT2 in addition to S100 and CD68, which may be helpful for differential diagnosis. Molecular detection showed that RDD may be related to the MAPK pathway, though these results are also ultimately not specific. The pathogenesis of RDD is yet to be elucidated, but recent studies suggest possible clonality of hyperproliferative histiocytes.

Intracavity generation of glioma stem cell-specific CAR macrophages primes locoregional immunity for postoperative glioblastoma therapy.

Glioblastoma multiforme (GBM) remains incurable despite aggressive implementation of multimodal treatments after surgical debulking. Almost all patients with GBM relapse within a narrow margin around the initial resected lesion due to postsurgery residual glioma stem cells (GSCs). Tracking and eradicating postsurgery residual GSCs is critical for preventing postoperative relapse of this devastating disease, yet effective strategies remain elusive. Here, we report a cavity-injectable nanoporter-hydrogel superstructure that creates GSC-specific chimeric antigen receptor (CAR) macrophages/microglia (MΦs) surrounding the cavity to prevent GBM relapse. Specifically, we demonstrate that the CAR gene-laden nanoporter in the hydrogel can introduce GSC-targeted CAR genes into MΦ nuclei after intracavity delivery to generate CAR-MΦs in mouse models of GBM. These CAR-MΦs were able to seek and engulf GSCs and clear residual GSCs by stimulating an adaptive antitumor immune response in the tumor microenvironment and prevented postoperative glioma relapse by inducing long-term antitumor immunity in mice. In an orthotopic patient-derived glioblastoma humanized mouse model, the combined treatment with nanoporter-hydrogel superstructure and CD47 antibody increased the frequency of positive immune responding cells and suppressed the negative immune regulating cells, conferring a robust tumoricidal immunity surrounding the postsurgical cavity and inhibiting postoperative glioblastoma relapse. Therefore, our work establishes a locoregional treatment strategy for priming cancer stem cell-specific tumoricidal immunity with broad application in patients suffering from recurrent malignancies.

Cell Recognition Using BP Neural Network Edge Computing.

This exploration is to solve the efficiency and accuracy of cell recognition in biological experiments. Neural network technology is applied to the research of cell image recognition. The cell image recognition problem is solved by constructing an image recognition algorithm. First, with an in-depth understanding of computer functions, as a basic intelligent algorithm, the artificial neural network (ANN) is widely used to solve the problem of image recognition. Recently, the backpropagation neural network (BPNN) algorithm has developed into a powerful pattern recognition tool and has been widely used in image edge detection. Then, the structural model of BPNN is introduced in detail. Given the complexity of cell image recognition, an algorithm based on the ANN and BPNN is used to solve this problem. The BPNN algorithm has multiple advantages, such as simple structure, easy hardware implementation, and good learning effect. Next, an image recognition algorithm based on the BPNN is designed and the image recognition process is optimized in combination with edge computing technology to improve the efficiency of algorithm recognition. The experimental results show that compared with the traditional image pattern recognition algorithm, the recognition accuracy of the designed algorithm for cell images is higher than 93.12%, so it has more advantages for processing the cell image algorithm. The results show that the BPNN edge computing can improve the scientific accuracy of cell recognition results, suggesting that edge computing based on the BPNN has a significant practical value for the research and application of cell recognition.

SOX30 Overexpression Reflects Tumor Invasive Degree, Lymph Node Metastasis and Predicts Better Survival in Colorectal Cancer Patients: A Long-Term Follow-Up Cohort Study.

Aims: Sex-determining region Y-box containing gene 30 (SOX30) takes part in the progression of several cancers, while its clinical engagement in colorectal cancer (CRC) is obscure. Therefore, this study aimed to explore the association of SOX30 with clinicopathological features and prognosis in CRC patients. Methods: Tumor and adjacent noncancerous specimens of 195 CRC patients who received resection were acquired. Furthermore, an immunohistochemistry assay was performed to detect SOX30 protein expression in these specimens; meanwhile, SOX30 mRNA expression was determined by reverse transcription-quantitative polymerase chain reaction assay in 95 out of 195 specimens. Moreover, clinical characteristics and survival data (follow-up duration median (range): 71.0 (7.0-95.0) months) of CRC patients were gathered. Results: SOX30 protein and mRNA expressions were both decreased in CRC tumor tissue compared to adjacent tissue (both P < 0.001). Furthermore, a negative correlation was found in tumor SOX30 protein expression with tumor size (P = 0.049), lymph node (LYN) metastasis (P = 0.018), T stage (P = 0.001), N stage (P = 0.034), and TNM stage (P = 0.001); tumor SOX30 mRNA expression was also negatively correlated with LYN metastasis (P = 0.001), T stage (P = 0.019), N stage (P = 0.004), and TNM stage (P < 0.001). Furthermore, tumor SOX30 protein expression was positively correlated with overall survival (OS) (P = 0.017), while tumor SOX30 mRNA expression was not correlated with OS (P = 0.070). Multivariate Cox's regression analysis illustrated that tumor SOX30 protein high expression was an independent factor for favorable OS (hazard ratio: 0.525, P = 0.034). Conclusions: SOX30 has potential as a biomarker for the progression and prognostication of CRC, which might improve the management of CRC.

Honokiol Induces Ferroptosis by Upregulating HMOX1 in Acute Myeloid Leukemia Cells.

Acute myeloid leukemia (AML) is one of the malignant hematological cancers with high mortality. Finding a more effective and readily available treatment is of the utmost importance. Here, we aimed to identify the anti-leukemia effect of a natural small molecule compound honokiol on a panel of AML cell lines, including THP-1, U-937, and SKM-1, and explored honokiol's potential biological pathways and mechanisms. The results showed that honokiol decreased the viability of the targeted AML cells, induced their cell cycle arrest at G0/G1 phase, and inhibited their colony-formation capacity. Honokiol also triggers a noncanonical ferroptosis pathway in THP-1 and U-937 cells by upregulating the level of intracellular lipid peroxide and HMOX1 significantly. Subsequent studies verified that HMOX1 was a critical target in honokiol-induced ferroptosis. These results reveal that honokiol is an effective anti-leukemia agent in AML cell lines and may be a potential ferroptosis activator in AML.

The evaluation of levosimendan in patients with acute myocardial infarction related ventricular septal rupture undergoing cardiac surgery: a prospective observational cohort study with propensity score analysis.

STUDY OBJECTIVE: The purpose of the present study was to evaluate the efficacy of levosimendan in patients with acute myocardial infarction related ventricular septal rupture (AMI-VSR) underwent cardiac surgery. DESIGN: Prospective observational cohort study with propensity score analysis. PATIENTS: There were 261 patients with AMI-VSR in our study. After 1:1 propensity matching, 106 patients (53 levosimendan and 53 control) were selected in the matched cohort. INTERVENTIONS: None. MEASUREMENTS: Patients who received levosimendan were assigned to the levosimendan group (n = 164). The patients who were not received were levosimendan assigned to the control group (n = 97). The levosimendan was initiated immediately after cardiopulmonary bypass. Then, it has been maintained during the postoperative 3 days. The poor outcomes were identified as follows: death and postoperative complications (postoperative stroke, low cardiac output syndromeneeded mechanical circulatory support after surgery, acute kidney injury (≥ stage III), postoperative infection or septic shock, new developed atrial fibrillation or ventricular arrhythmias). MAIN RESULTS: Before matching, the control group had more length of ICU stay (6.69 ± 3.90 d vs. 5.20 ± 2.24 d, p < 0.001) and longer mechanical ventilation time (23 h, IQR: 16-53 h vs. 16 h, IQR: 11-23 h, p < 0.001). Other postoperative outcomes have not shown significant differences between two groups. After matching, no significant difference was found between both groups for all postoperative outcomes. The Kaplan-Meier survivul estimate and log-rank test showed that the 90-day survival had no significant differences between two groups before and after matching. CONCLUSION: Our study found that a low-dose infusion of levosimendan in AMI-VSR patients underwent surgical repair did not associated with positively affect to postoperative outcomes.

Origami-inspired folding assembly of dielectric elastomers for programmable soft robots.

Origami has become an optimal methodological choice for creating complex three-dimensional (3D) structures and soft robots. The simple and low-cost origami-inspired folding assembly provides a new method for developing 3D soft robots, which is ideal for future intelligent robotic systems. Here, we present a series of materials, structural designs, and fabrication methods for developing independent, electrically controlled origami 3D soft robots for walking and soft manipulators. The 3D soft robots are based on soft actuators, which are multilayer structures with a dielectric elastomer (DE) film as the deformation layer and a laser-cut PET film as the supporting flexible frame. The triangular and rectangular design of the soft actuators allows them to be easily assembled into crawling soft robots and pyramidal- and square-shaped 3D structures. The crawling robot exhibits very stable crawling behaviors and can carry loads while walking. Inspired by origami folding, the pyramidal and square-shaped 3D soft robots exhibit programmable out-of-plane deformations and easy switching between two-dimensional (2D) and 3D structures. The electrically controllable origami deformation allows the 3D soft robots to be used as soft manipulators for grasping and precisely locking 3D objects. This work proves that origami-inspired fold-based assembly of DE actuators is a good reference for the development of soft actuators and future intelligent multifunctional soft robots.