Biosynthesis and Anticancer Activity of Genistein Glycoside Derivatives.

As a beneficial natural flavonoid, genistein has demonstrated a wide range of biological functions via regulating a number of targets and signaling pathways, such as anti-cancer, antioxidant, antibacterial, antiinflammatory, antifungal, antiviral, iron chelation, anti-obesity, anti-diabetes, and anti-hypertension. PubMed/Medline and Web of Science were searched using appropriate keywords until the end of December 2023. Despite its many potential benefits, genistein's clinical application is limited by low hydrophilicity, poor solubility, and suboptimal bioavailability due to its structure. These challenges can be addressed through the conversion of genistein into glycosides. Glycosylation of active small molecules may enhance their solubility, stability, and biological activity. In recent years, extensive research has been conducted on the synthesis, properties, and anticancer activity of glycoconjugates. Previous reviews were devoted to discussing the biological activities of genistin, with a little summary of the biosynthesis and the structure-activity relationship for their anticancer activity of genistein glycoside derivatives. Therefore, we summarized recent advances in the biosynthesis of genistein glycosylation and discussed the antitumor activities of genistein glycoside derivatives in a structure-activity relationship, which may provide important information for further development of genistein derivatives.

Inhibiting autophagy enhanced mitotic catastrophe-mediated anticancer immune responses by regulating the cGAS-STING pathway.

Given the limitations of the response rate and efficacy of immune checkpoint inhibitors (ICIs) in clinical applications, exploring new therapeutic strategies for cancer immunotherapy is necessary. We found that 5-(3,4,5-trimethoxybenzoyl)-4-methyl-2-(p-tolyl)imidazole (BZML), a microtubule-targeting agent, exhibited potent anticancer activity by inducing mitotic catastrophe in A549/Taxol and L929 cells. Nuclear membrane disruption and nuclease reduction provided favorable conditions for cGAS-STING pathway activation in cells with mitotic catastrophe. Similar results were obtained in paclitaxel-, docetaxel- and doxorubicin-induced mitotic catastrophe in various cancer cells. Notably, the surface localization of CALR and MHC-I and the release of HMGB1 were also significantly increased in cells with mitotic catastrophe, but not in apoptotic cells, suggesting that mitotic catastrophe is an immunogenic cell death. Furthermore, activated CD8+T cells enhanced the anticancer effects originating from mitotic catastrophe induced by BZML. Inhibiting the cGAS-STING pathway failed to affect BZML-induced mitotic catastrophe but could inhibit mitotic catastrophe-mediated anticancer immune effects. Interestingly, the expression of p-TBK1 first increased and then declined; however, autophagy inhibition reversed the decrease in p-TBK1 expression and enhanced mitotic catastrophe-mediated anticancer immune effects. Collectively, the inhibition of autophagy can potentiate mitotic catastrophe-mediated anticancer immune effects by regulating the cGAS-STING pathway, which explains why the anticancer immune effects induced by chemotherapeutics have not fully exerted their therapeutic efficacy in some patients and opens a new area of research in cancer immunotherapy.

Study on human-SRL synchronized walking based on coupled impedance.

Introduction: Supernumerary robotic limbs (SRL) is a novel category of wearable robotics. Unlike prostheses (compensation for human limbs) and exoskeletons (augmentation of human limbs), SRL focuses on expanding human limbs and enhancing human activities, perception, and operation through the mutual collaboration of mechanical limbs and human limbs. The SRL of lower limbs are attached to the human waist, synchronized with the human walking in the forward direction, and can carry weight independently in the vertical direction. Methods: In order to enhance the synchronization performance of the human-machine system during walking and minimize interference with human gait, it is essential to investigate the coupling dynamics within the human-SRL system. To facilitate our research, this paper focuses on relatively ideal working conditions: level road surfaces, no additional weight-bearing on the SRL, and humans walking in a straight line without any turns. We build upon the passive dynamic walking theory and utilize the human-SRL system model established by MIT to develop a coupling system model. Through numerical simulations, we identify the optimal values for the stiffness and damping coefficients of the human-machine connection. Additionally, we have designed the wheel-legged SRL structure and constructed the SRL control system for experimental validation. Results: It is found that a better synchronization of the human-machine walking process can be achieved by configuring suitable spring and damping units in the human-machine connection part. Discussion: In this study, we explored the concept of SRL and its potential benefits for enhancing human motion, conducting simulations and experiments based on the coupled dynamics of human-SRL systems. The results indicate that by equipping the human-machine connection component with suitable spring and damping units, synchronization during the walking process can be improved.

Perspectives and mechanisms for targeting mitotic catastrophe in cancer treatment.

Mitotic catastrophe is distinct from other cell death modes due to unique nuclear alterations characterized as multi and/or micronucleation. Mitotic catastrophe is a common and virtually unavoidable consequence during cancer therapy. However, a comprehensive understanding of mitotic catastrophe remains lacking. Herein, we summarize the anticancer drugs that induce mitotic catastrophe, including microtubule-targeting agents, spindle assembly checkpoint kinase inhibitors, DNA damage agents and DNA damage response inhibitors. Based on the relationships between mitotic catastrophe and other cell death modes, we thoroughly evaluated the roles played by mitotic catastrophe in cancer treatment as well as its advantages and disadvantages. Some strategies for overcoming its shortcomings while fully utilizing its advantages are summarized and proposed in this review. We also review how mitotic catastrophe regulates cancer immunotherapy. These summarized findings suggest that the induction of mitotic catastrophe can serve as a promising new therapeutic approach for overcoming apoptosis resistance and strengthening cancer immunotherapy.

Association between axial length and HDL in children: a hospital-based cross-sectional study.

BACKGROUND: To analyze the relationship between axial length and levels of high-density lipoprotein (HDL) cholesterol in children. METHODS: A retrospective, hospital-based cross-sectional research with 69 right eyes from 69 children who underwent health examination by Zhejiang Provincial People's Hospital was carried out. The participants were split into three groups: Group A (axial length < = 23 mm), Group B (axial length 23-24 mm), and Group C (axial length > 24 mm). Demographic epidemiological information, blood biochemical parameters and ophthalmic characteristics including refractive status and ocular geometric parameters were obtained and analyzed. RESULTS: 69 right eyes from 69 patients (25 males and 44 females) with a median age of 10.00 years old (IQR: 8.00-11.00 years) were included in the study. Within Group A, there were a total of 17 individuals; Group B consisted of 22 individuals; Group C included 30 individuals. The mean axial length of three groups was 22.148(0.360), 23.503(0.342) and 24.770(0.556) mm, respectively (p < 0.0001). The mean HDL levels were significantly different in three groups are 1.824(0.307), 1.485(0.253) and 1.507 (0.265) mmol/L, respectively. By applying a Pearson Coefficient, we evaluated the association between axial length and HDL and discovered that there was a statistically significant (p = 0.00025) and adverse (R = -0.43) association between axial length and HDL. CONCLUSIONS: We concluded from our study that there was a significantly inverse relationship between axial length and the levels of HDL in children.

Comparison of Aurolab Aqueous Drainage Implant with Ahmed Glaucoma Valve for Refractory Glaucoma: A Meta-Analysis.

BACKGROUND: Ahmed glaucoma valve (AGV) is a common surgical method for the treatment of refractory glaucoma.Aurolab aqueous drainage implant (AADI) is a novel surgical method which has been applied in clinical practice in recent years. OBJECTIVE: The purpose of this study was to compare the efficacy and safety of the AADI and the AGV for the treatment of refractory glaucoma. METHODS: We comprehensively searched four databases, including PubMed, Embase, Web of Science, and the Cochrane Library databases, selecting the relevant studies. The continuous variables, namely, intraocular pressure reduction (IOPR) and a reduction in antiglaucoma medication (AGMR), were pooled by the weighted mean differences (WMDs), and the dichotomous outcomes, including success rates and complications, were pooled by the odds ratio (OR). RESULTS: A total of 825 eyes from 820 patients from six studies were included. The WMDs of the IOPR between the AADI and the AGV implant were 0.58 (95% CI: 0.07-1.09) at 3 months, 0.44 (95% CI: 0.11-0.77) at 6 months, 2.20 (95% CI: 0.63-3.77) at 12 months, and 3.24 (95% CI: 1.73-4.75) at follow-up endpoint. Significant difference was detected between the two groups at any point in time. The WMDs of the AGMR between the AADI and the AGV implant were 0.87 (95% CI: 0.61-1.13) at 6 months, 1.04 (95% CI: 0.66-1.42) at 12 months, and 0.93 (95% CI: 0.52-1.34) at the follow-up endpoint; the differences reached statistical significance at any point in time. The pooled ORs comparing the AADI with the AGV were 3.64 (95% CI: 2.44-5.45) for the complete success rate and 1.72 (95% CI: 1.24-2.39) for qualified success rate; significant difference was detected between the two groups. There were no significant differences between the AADI and the AGV implant on the rates of adverse events. CONCLUSIONS: The AADI is more effective in both its surgical success rate and reducing IOP and AGM. And the two implants may have comparable incidences of adverse events.

Anticancer activity of oleanolic acid and its derivatives modified at A-ring and C-28 position.

Oleanolic acid (OA) is a five-ring triterpenoid compound, which is widely present in plants. Due to a wide range of pharmacological activities, oleanolic acid has attracted more and more attention. However, oleanolic acid is insoluble in water and has low bioavailability, which limits its clinical application. In this review, we focus on summarizing the anti-cancer activity and mechanism of the A ring or C-28 carboxyl modified derivatives of OA since 2015, to determine the strength of its anti-cancer effectiveness and evaluate whether it could be used as a clinical anti-cancer drug.

Cost Function Determination for Human Lifting Motion via the Bilevel Optimization Technology.

Investigating the optimal control strategy involved in human lifting motion can provide meritorious insights on designing and controlling wearable robotic devices to release human low-back pain and fatigue. However, determining the latent cost function regarding this motion remains challenging due to the complexities of the human central nervous system. Recently, it has been discovered that the underlying cost function of a biological motion can be identified from an inverse optimization control (IOC) issue, which can be handled via the bilevel optimization technology. Inspired by this discovery, this work is dedicated to studying the underlying cost function of human lifting tasks through the bilevel optimization technology. To this end, a nested bilevel optimization approach is developed by integrating particle swarm optimization (PSO) with the direction collocation (DC) method. The upper level optimizer leverages particle swarm optimization to optimize weighting parameters among different predefined performance criteria in the cost function while minimizing the kinematic error between the experimental data and the result predicted by the lower level optimizer. The lower level optimizer implements the direction collocation method to predict human kinematic and dynamic information based on the human musculoskeletal model inserted into OpenSim. Following after a benchmark study, the developed method is evaluated by experimental tests on different subjects. The experimental results reveal that the proposed method is effective at finding the cost function of human lifting tasks. Thus, the proposed method could be regarded as a paramount alternative in the predictive simulation of human lifting motion.

Autophagy and cancer treatment: four functional forms of autophagy and their therapeutic applications.

Cancer is the leading cause of death worldwide. Drugs play a pivotal role in cancer treatment, but the complex biological processes of cancer cells seriously limit the efficacy of various anticancer drugs. Autophagy, a self-degradative system that maintains cellular homeostasis, universally operates under normal and stress conditions in cancer cells. The roles of autophagy in cancer treatment are still controversial because both stimulation and inhibition of autophagy have been reported to enhance the effects of anticancer drugs. Thus, the important question arises as to whether we should try to strengthen or suppress autophagy during cancer therapy. Currently, autophagy can be divided into four main forms according to its different functions during cancer treatment: cytoprotective (cell survival), cytotoxic (cell death), cytostatic (growth arrest), and nonprotective (no contribution to cell death or survival). In addition, various cell death modes, such as apoptosis, necrosis, ferroptosis, senescence, and mitotic catastrophe, all contribute to the anticancer effects of drugs. The interaction between autophagy and these cell death modes is complex and can lead to anticancer drugs having different or even completely opposite effects on treatment. Therefore, it is important to understand the underlying contexts in which autophagy inhibition or activation will be beneficial or detrimental. That is, appropriate therapeutic strategies should be adopted in light of the different functions of autophagy. This review provides an overview of recent insights into the evolving relationship between autophagy and cancer treatment.

Survivin suppression heightens BZML-induced mitotic catastrophe to overcome multidrug resistance by removing therapy-induced senescent A549/Taxol cells.

Mitotic catastrophe (MC) is a newly identified type of anticancer mechanism for multidrug resistance (MDR) prevention. However, the long cellular death process resulting from MC is not beneficial for anticancer treatment. BZML is a novel colchicine-binding site inhibitor which can overcome MDR by inducing MC; however, BZML-induced MC cells underwent a long cellular death process. Thus, to improve anticancer therapies based on drug-induced MC, BZML-induced MC was served as a model to further study the underlying molecular mechanisms in the process of MC. Here, BZML could induce p53-dependent senescence in A549/Taxol cells, a MDR cell line. This senescence was a secondary effect of MC in overcoming MDR. During MC, BZML-induced destruction of protein-degradation system contributed not only to an increase of p53 protein but also to the accumulation of survivin in nucleus of A549/Taxol cells. Importantly, the nuclear accumulation of survivin was not the inducer but the result of BZML-induced MC, and it promoted the survival of senescent cells. Moreover, it provided additional vulnerability and critical opportunities for sequentially applied therapies. Further, targeting survivin with YM155 accelerated the death of MC cells by timely eliminating therapy-induced senescent cells and strengthening the efficiency of BZML in overcoming MDR in A549/Taxol cells. Collectively, nuclear accumulation of survivin delayed cellular death during MC by promoting the survival of BZML-induced senescent A549/Taxol cells. Moreover, "one-two punch" approach to cancer treatment based on combination therapy with YM155 for survivin suppression might be a new strategy for potentiating MC to overcome MDR.

A Review on Metal-Organic Framework-Derived Porous Carbon-Based Novel Microwave Absorption Materials.

The development of microwave absorption materials (MAMs) is a considerable important topic because our living space is crowed with electromagnetic wave which threatens human's health. And MAMs are also used in radar stealth for protecting the weapons from being detected. Many nanomaterials were studied as MAMs, but not all of them have the satisfactory performance. Recently, metal-organic frameworks (MOFs) have attracted tremendous attention owing to their tunable chemical structures, diverse properties, large specific surface area and uniform pore distribution. MOF can transform to porous carbon (PC) which is decorated with metal species at appropriate pyrolysis temperature. However, the loss mechanism of pure MOF-derived PC is often relatively simple. In order to further improve the MA performance, the MOFs coupled with other loss materials are a widely studied method. In this review, we summarize the theories of MA, the progress of different MOF-derived PC­based MAMs, tunable chemical structures incorporated with dielectric loss or magnetic loss materials. The different MA performance and mechanisms are discussed in detail. Finally, the shortcomings, challenges and perspectives of MOF-derived PC­based MAMs are also presented. We hope this review could provide a new insight to design and fabricate MOF-derived PC-based MAMs with better fundamental understanding and practical application.

Effects of illness perceptions on health-related quality of life in patients with rheumatoid arthritis in China.

OBJECTIVES: For patients with rheumatoid arthritis (RA) in China, little is known of how their illness perceptions affect their health-related quality of life (HRQoL). The present study investigated associations between specific illness perceptions due to RA and HRQoL features. METHODS: For 191 patients with RA, illness perceptions were measured using the Brief Illness Perceptions Questionnaire (BIPQ) comprising 8 domains. HRQoL was determined with the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). Multivariate linear regression analyses were performed. RESULTS: The overall BIPQ of patients with RA was 49.09 ± 11.06. The highest and lowest scores were for concern (9.15 ± 1.81) and personal control (4.30 ± 2.52), respectively. Multivariate stepwise regression analyses showed that the overall BIPQ was significantly negatively associated with each HRQoL feature, and HRQoL total score (ß = - 0.343, P < 0.001, 95% CI - 7.080 to - 4.077). Positive associations between BIPQ features and HRQoL included personal control (ß = 0.119, P = 0.004, 95% CI 2.857-14.194) and treatment control (ß = 0.084, P = 0.029, 95% CI 0.640-12.391). Negative associations with HRQoL were identity (ß = - 0.105, P = 0.034, 95% CI - 13.159 to - 0.430) and emotional response (ß = - 0.207, P < 0.001, 95% CI - 18.334 to - 6.811). CONCLUSIONS: Patients with RA in China perceive their illness in ways that affect their HRQoL. These results suggest that strategies that target these perceptions may improve the quality of life of these patients.

Quality changes in high pressure processed tan mutton during storage.

The current study investigated the effects of high pressure (HP) treatment at 200 MPa and 500 MPa on quality characteristics of post-rigor tan mutton stored for 7 days at 4 °C, and textural changes were monitored during storage by means of the stress relaxation test. Application of 500 MPa high pressure significantly increased the elasticity and stiffness of meat after 7 days of storage (P < 0.05), accompanied by a lighter and less red appearance and markedly enhanced centrifugal loss during storage campared to untreated (P < 0.05). High pressure treatment at 200 MPa also substantially increased the lightness of samples throughout storage (P < 0.05), and showed a significant increase in stiffness at the end of storage (P < 0.05). Immunoblotting and electrophoresis (SDS-PAGE) analysis of key structural proteins revealed that myosin heavy chain denaturation began at 200 MPa, while actin denaturation occurred at 500 MPa. Troponin-T was continuously degraded in different treatments as storage progressed, and 200 MPa treatment and untreated represented similar degradation patterns, while 500 MPa treatment displayed more intense intact troponin-T at 38 kDa degradation. Results suggest that HP induced changes in cytoskeleton proteins, thereby affecting texture, water holding properties and lightness.

A cross-sectional survey of knowledge, attitude and practice associated with COVID-19 among undergraduate students in China.

BACKGROUND: The COVID-19 pandemic has become a great threat to public health, which has greatly impacted the study and life of undergraduate students in China. This study aims to perform a survey of their knowledge, attitude and practice (KAP) associated with COVID-19. METHODS: A cross-sectional survey was designed to gather information regarding the COVID-19 related KAP among undergraduates during the home isolation in the outbreak. Subjects were recruited from 10 universities in Shaanxi Province, China. Enrollees voluntarily submitted their answers to a pre-designed questionnaire online. RESULTS: A total of 872 subjects (female, 534; male, 338) were enrolled with ages from 17 to 25 years old. This cohort included 430 medical and 442 non-medical students, 580 freshmen and 292 higher school year students. There were 453 from public schools and 442 from private school, residing in 28 regions and provinces at the time of study. Results showed that appropriate knowledge was acquired by 82.34% subjects; the levels were significantly higher in undergraduates from public universities and medical majors than those from private schools and non-medical majors (p<0.05). 73.81% subjects reported positive attitudes; females showed significantly higher levels of positive attitudes than males (p<0.05). Proactive practice was found in 87.94% subjects. Using a common scoring method, the overall scores for Knowledge, Attitude and Practice were 4.12 ± 0.749 (range: 0 ~ 5), 8.54 ± 1.201 (range: 0 ~ 10), and 8.91 ± 1.431 (range: 0 ~ 10), respectively. There was a positive correlation between attitude and practice (r = 0.319, p < 0.05) in the whole study group. Total KAP score was 21.57 ± 2.291 (range: 0 ~ 25), which was significantly different between gender groups and major groups. CONCLUSIONS: Most undergraduates acquired necessary knowledge, positive attitude and proactive practice in response to COVID-19 outbreak; but their KAP scores significantly varied by gender, major and school types.

miR-125b Suppresses Proliferation and Invasion by Targeting MCL1 in Gastric Cancer.

Understanding the molecular mechanisms underlying gastric cancer progression contributes to the development of novel targeted therapies. In this study, we found that the expression levels of miR-125b were strongly downregulated in gastric cancer and associated with clinical stage and the presence of lymph node metastases. Additionally, miR-125b could independently predict OS and DFS in gastric cancer. We further found that upregulation of miR-125b inhibited the proliferation and metastasis of gastric cancer cells in vitro and in vivo. miR-125b elicits these responses by directly targeting MCL1 (myeloid cell leukemia 1), which results in a marked reduction in MCL1 expression. Transfection of miR-125b sensitizes gastric cancer cells to 5-FU-induced apoptosis. By understanding the function and molecular mechanisms of miR-125b in gastric cancer, we may learn that miR-125b has the therapeutic potential to suppress gastric cancer progression and increase drug sensitivity to gastric cancer.