Remote coupling of electrical and mechanical cues by diurnal photothermal irradiation synergistically promotes bone regeneration.

Recapitulating the natural extracellular physical microenvironment has emerged as a promising method for tissue regeneration, as multiple physical interventions, including ultrasound, thermal and electrical therapy, have shown great potential. However, simultaneous coupling of multiple physical cues to highly bio-mimick natural characteristics for improved tissue regeneration still remains formidable. Coupling of intrinsic electrical and mechanical cues has been regarded as an effective way to modulate tissue repair. Nevertheless, precise and convenient manipulation on coupling of mechano-electrical signals within extracellular environment to facilitate tissue regeneration remains challengeable. Herein, a photothermal-sensitive piezoelectric membrane was designed for simultaneous integration of electrical and mechanical signals in response to NIR irradiation. The high-performance mechano-electrical coupling under NIR exposure synergistically triggered the promotion of osteogenic differentiation of stem cells and enhances bone defect regeneration by increasing cellular mechanical sensing, attachment, spreading and cytoskeleton remodeling. This study highlights the coupling of mechanical signals and electrical cues for modulation of osteogenesis, and sheds light on alternative bone tissue engineering therapies with multiple integrated physical cues for tissue repair.

Dietary patterns and the risk of tuberculosis-drug-induced liver injury: a cohort study.

Background and purpose: Nutrition is associated with tuberculosis drug-induced liver injury (TBLI). How dietary patterns relate to tuberculosis drug-induced liver injury is still unknown. The objective of this study is to explore the relation between dietary patterns and the risk of tuberculosis drug-induced liver injury. Methods: This cohort study was conducted at two hospitals in Shandong Province, China, between 2011 and 2013. A total of 605 tuberculosis patients were included in the final analysis. The blood aspartate aminotransferase or alanine aminotransferase level was monitored through the 6-month tuberculosis treatment. The semi-quantitative food frequency questionnaires were used to survey dietary intake in the second month of the tuberculosis treatment. The China Healthy Diet Index (CHDI), which was previously validated in the Chinese population, was used as an a priori dietary pattern. A posteriori dietary patterns were extracted by principal component analysis (PCA). Results: The CHDI was negatively associated with the risk of liver injury [adjusted odds ratio (aOR) per standard deviation (SD) (95% CI): 0.61 (0.40-0.94)] and liver dysfunction [aOR per SD (95% CI): 0.47 (0.35-0.64)] in the multivariate logistic model. A positive association between "Organ meat, poultry, and vegetable oil" dietary pattern scores (extracted by PCA) and the risk of liver injury [aOR (95% CI): 3.02 (1.42-6.41)] and liver dysfunction [aOR (95% CI): 1.83 (1.09-3.05)] was observed. Conclusion: In conclusion, a high CHDI score was a protective factor for tuberculosis drug-induced liver injury, while the "Organ meat, poultry, and vegetable oil" dietary pattern, which was rich in organ meat, poultry, and vegetable oil and low in vegetables, was an independent risk factor for tuberculosis drug-induced liver injury.

Risk Factors of Poststroke Cognitive Impairment: A Meta-Analysis.

OBJECTIVE: To explore the potential risk factors of post stroke cognitive impairment (PSCI) by conducting a meta-analysis. METHODS: Literature search was performed in databases (PubMed, Embase, Web of Science, CNKI) using keywords of PSCI. Cochrane ROB tool was adopted for evaluating the quality of the included studies. Afterwards, data was independently extracted by 2 investigators. Heterogeneity was quantified across studies by Chi-squared-based Q statistic test and I2 statistic. The random-effects model or fixed-effects model was employed to compute the pooled estimates depends on whether the heterogeneity was significant (I2 > 50% or P < .05) or not. Publication bias was evaluated by the funnel plot and Egger's test. Sensitivity analysis was accomplished through eliminating studies 1 at a time to evaluate the stability of the pooled estimates. RESULTS: 23 high-quality studies with 13322 patients were included. Compared with patients with no cognitive impairment, PSCI was more likely to develop in the elderly (pooled MD = 3.58, 95% CI = [1.82, 5.34]), female (pooled RR = 1.23, 95% CI = [1.07, 1.41]), or less-educated (pooled MD = -1.63, 95% CI = [-2.96, -.31]) patients with a history of hypertension (pooled RR = 1.07, 95% CI = [1.03, 1.11]), diabetes mellitus (pooled RR = 1.10, 95% CI = [1.03, 1.17]), atrial fibrillation (pooled RR = 1.38, 95% CI = [1.10, 1.74]), or stroke (pooled RR = 1.36, 95% CI = [1.09, 1.70]). Smoking did not affect the development of PSCI in patients (pooled RR = .96, 95% CI = [.78, 1.19]). Ischemic heart disease and region represented the sources of significant heterogeneity across studies. The pooled estimates were robust, and no publication bias was seen. CONCLUSION: Age, gender, education, hypertension, diabetes mellitus, atrial fibrillation, and stroke were the risk factors of PSCI. Controlling these risk factors can help prevent PSCI.

Realizing the Efficient Dissolution of Drag Reducer upon pH-Induced Demulsification of Inverse Polymer Emulsion.

The increasing exploitation of fossil resources needs to shift people's attention to developing unconventional reservoir resources. Polyacrylamide-based emulsion drag reducers can effectively reduce the turbulence of fracturing fluid and improve oil recovery, but their release effect is poor, which limits their practical application. Here, we constructed a pH-responsive inverse polymer emulsion of poly(acrylamide-2-acrylamido-2-methylpropanesulfonic acid). Interestingly, HOA/Tween 80 exhibits remarkable pH-responsive behavior, which enables the monomer emulsion to change the type of emulsion under pH stimulation. Our results propose that the P(AM-AMPS) polymer emulsion is eluted with the same aqueous phase as the W/O P(AM-AMPS) polymer emulsion, thereby achieving the effect of drag reduction. P(AM-AMPS) can be rapidly released from the inverse polymer emulsion within 70 s upon pH stimulation, the drag reduction rate of which was 60.4%. Obviously, the inverse polymer emulsion prepared by a pH-responsive surfactant not only has good stability but also can achieve rapid release of the polymer upon pH stimulation, which supplies an interesting indication to explain why a balance exists between the stability of the emulsion and release of P(AM-AMPS).

A holistic platform for accelerating sorbent-based carbon capture.

Reducing carbon dioxide (CO2) emissions urgently requires the large-scale deployment of carbon-capture technologies. These technologies must separate CO2 from various sources and deliver it to different sinks1,2. The quest for optimal solutions for specific source-sink pairs is a complex, multi-objective challenge involving multiple stakeholders and depends on social, economic and regional contexts. Currently, research follows a sequential approach: chemists focus on materials design3 and engineers on optimizing processes4,5, which are then operated at a scale that impacts the economy and the environment. Assessing these impacts, such as the greenhouse gas emissions over the plant's lifetime, is typically one of the final steps6. Here we introduce the PrISMa (Process-Informed design of tailor-made Sorbent Materials) platform, which integrates materials, process design, techno-economics and life-cycle assessment. We compare more than 60 case studies capturing CO2 from various sources in 5 global regions using different technologies. The platform simultaneously informs various stakeholders about the cost-effectiveness of technologies, process configurations and locations, reveals the molecular characteristics of the top-performing sorbents, and provides insights on environmental impacts, co-benefits and trade-offs. By uniting stakeholders at an early research stage, PrISMa accelerates carbon-capture technology development during this critical period as we aim for a net-zero world.

Advances in biomaterials for oral-maxillofacial bone regeneration: spotlight on periodontal and alveolar bone strategies.

The intricate nature of oral-maxillofacial structure and function, coupled with the dynamic oral bacterial environment, presents formidable obstacles in addressing the repair and regeneration of oral-maxillofacial bone defects. Numerous characteristics should be noticed in oral-maxillofacial bone repair, such as irregular morphology of bone defects, homeostasis between hosts and microorganisms in the oral cavity and complex periodontal structures that facilitate epithelial ingrowth. Therefore, oral-maxillofacial bone repair necessitates restoration materials that adhere to stringent and specific demands. This review starts with exploring these particular requirements by introducing the particular characteristics of oral-maxillofacial bones and then summarizes the classifications of current bone repair materials in respect of composition and structure. Additionally, we discuss the modifications in current bone repair materials including improving mechanical properties, optimizing surface topography and pore structure and adding bioactive components such as elements, compounds, cells and their derivatives. Ultimately, we organize a range of potential optimization strategies and future perspectives for enhancing oral-maxillofacial bone repair materials, including physical environment manipulation, oral microbial homeostasis modulation, osteo-immune regulation, smart stimuli-responsive strategies and multifaceted approach for poly-pathic treatment, in the hope of providing some insights for researchers in this field. In summary, this review analyzes the complex demands of oral-maxillofacial bone repair, especially for periodontal and alveolar bone, concludes multifaceted strategies for corresponding biomaterials and aims to inspire future research in the pursuit of more effective treatment outcomes.

Study on an Automatic Classification Method for Determining the Malignancy Grade of Glioma Pathological Sections Based on Hyperspectral Multi-Scale Spatial-Spectral Fusion Features.

This study describes a novel method for grading pathological sections of gliomas. Our own integrated hyperspectral imaging system was employed to characterize 270 bands of cancerous tissue samples from microarray slides of gliomas. These samples were then classified according to the guidelines developed by the World Health Organization, which define the subtypes and grades of diffuse gliomas. We explored a hyperspectral feature extraction model called SMLMER-ResNet using microscopic hyperspectral images of brain gliomas of different malignancy grades. The model combines the channel attention mechanism and multi-scale image features to automatically learn the pathological organization of gliomas and obtain hierarchical feature representations, effectively removing the interference of redundant information. It also completes multi-modal, multi-scale spatial-spectral feature extraction to improve the automatic classification of glioma subtypes. The proposed classification method demonstrated high average classification accuracy (>97.3%) and a Kappa coefficient (0.954), indicating its effectiveness in improving the automatic classification of hyperspectral gliomas. The method is readily applicable in a wide range of clinical settings, offering valuable assistance in alleviating the workload of clinical pathologists. Furthermore, the study contributes to the development of more personalized and refined treatment plans, as well as subsequent follow-up and treatment adjustment, by providing physicians with insights into the underlying pathological organization of gliomas.

The Oncolytic virus VT1092M and an Anti-PD-L1 antibody synergize to induce systemic antitumor immunity in a murine bilateral tumor model.

This study investigated the synergistic potential of an oncolytic herpes simplex virus armed with interleukin 12 (VT1092M) in combination with immune checkpoint inhibitors for enhancing antitumor responses. The potential of this combination treatment to induce systemic antitumor immunity was assessed using bilateral subcutaneous tumor and tumor re-challenge mouse models. The antitumor efficacy of various OV and ICI treatment combinations and the underlying mechanisms were explored through diverse analytical techniques, including flow cytometry and RNA sequencing. Using VT1092M, either alone or in combination with an anti-PD-L1 antibody, significantly reduced the sizes of both the injected and untreated abscopal tumors in a bilateral tumor mouse model. The combination therapy demonstrated superior antitumor efficacy to the other treatment conditions tested, which was accompanied by an increase in T cell numbers and CD8+T cell activation. Results from the survival and tumor re-challenge experiments showed that the combination therapy elicited long-term, tumor-specific immune responses, which were associated with tumor clearance and prolonged survival. Immune cell depletion assays identified CD8+T cells as the crucial mediators of systemic antitumor immunity during combination therapy. In conclusion, the combination of VT1092M and PD-L1 blockade emerged as a potent inducer of antitumor immune responses, surpassing the efficacy of each monotherapy. This synergistic approach holds promise for achieving robust and sustained antitumor immunity, with potential implications for preventing tumor metastasis in patients with cancer.

Polarization evolution on higher and hybrid-order Poincaré spheres with coaxial polarization holograms.

Based on the tensor polarization holography theory, we propose a simple and convenient method in the recording material, phenanthrenequinone-doped polymethylmethacrylate, to generate beams on higher and hybrid-order Poincaré spheres, and realize their polarization evolution on the spheres by combining the recorded phase with the Pancharatnam-Berry phase. By simultaneously adjusting the polarization azimuth angle and relative phase of the recorded waves, independent phase-shifts can be imparted onto two orthogonal circular polarization states in reconstruction process of polarization holography. The beams on basic Poincaré sphere are transformed into that on arbitrary higher or hybrid-order Poincaré spheres. We get the Poincaré spheres' type and polarization distribution of the reconstructed wave by interferometry and polarizer, and the results match well with the theoretical predictions.

The specificities, influencing factors, and medical implications of bone circadian rhythms.

Physiological processes within the human body are regulated in approximately 24-h cycles known as circadian rhythms, serving to adapt to environmental changes. Bone rhythms play pivotal roles in bone development, metabolism, mineralization, and remodeling processes. Bone rhythms exhibit cell specificity, and different cells in bone display various expressions of clock genes. Multiple environmental factors, including light, feeding, exercise, and temperature, affect bone diurnal rhythms through the sympathetic nervous system and various hormones. Disruptions in bone diurnal rhythms contribute to the onset of skeletal disorders such as osteoporosis, osteoarthritis and skeletal hypoplasia. Conversely, these bone diseases can be effectively treated when aimed at the circadian clock in bone cells, including the rhythmic expressions of clock genes and drug targets. In this review, we describe the unique circadian rhythms in physiological activities of various bone cells. Then we summarize the factors synchronizing the diurnal rhythms of bone with the underlying mechanisms. Based on the review, we aim to build an overall understanding of the diurnal rhythms in bone and summarize the new preventive and therapeutic strategies for bone disorders.

Hyperspectral imaging for in situ visual assessment of Industrial-Scale ginseng.

In industrial production, the timely assessment of ginseng-derived ingredients is crucial and requires nondestructive techniques for identifying and analyzing composition. Hyperspectral imaging (HSI) effectively visualizes the three-dimensional spatial distribution of phytochemicals in dried ginseng. This study explores the in-situ prediction and visualization of moisture content (MC) and ginsenoside content (GC) in thermally processed ginseng using dual-band HSI. We collected hyperspectral images from 216 raw ginseng samples, which underwent dimensionality reduction, noise reduction, and feature enhancement via Principal Component Analysis (PCA) and Minimum Noise Separation (MNF). Linear regression models were developed following these pretreatments and evaluated using a validation set. The PCA-based models demonstrated superior performance over those based on MNF, especially in predicting GC in the near-infrared (NIR) spectrum. Similarly, models predicting MC in the visible spectrum showed favorable results. HSI enables rapid generation of distribution maps, facilitating real-time imaging for commercial applications. Repeated drying cycles and increased duration primarily affect the textural characteristics and visible color of the ginseng surface, without significantly altering its intrinsic properties. The deployment of this predictive model alongside real-time content inversion using HSI technology holds promise for integrating visual and intelligent quality monitoring in the trade of valuable herbal commodities.

Social Isolation, Loneliness, and Risk of Microvascular Complications Among Individuals With Type 2 Diabetes Mellitus.

RATIONALE & OBJECTIVE: Social disconnection has been associated with poor cardiometabolic health. This study sought to investigate the associations of social isolation and loneliness with diabetic microvascular complications (DMC) among individuals with type 2 diabetes mellitus (T2DM) and compare these associations to those related to traditional risk factors. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: A total of 24,297 UK Biobank participants with T2DM and no DMC at baseline. EXPOSURE: Social isolation and loneliness measured using self-reported questionnaires. OUTCOME: The incidence of DMC defined as a composite of diabetic kidney disease, diabetic retinopathy, or diabetic neuropathy. ANALYTICAL APPROACH: Multivariable cause-specific hazards regression. To compare the relative importance of social disconnection with other established factors, the R2 values of the Cox models were calculated. RESULTS: During a median follow-up of 12.6 years, 5,530 patients were documented to develop DMC (3,458 with diabetic kidney disease, 2,255 with diabetic retinopathy, and 1,146 with diabetic neuropathy). The highest level of social isolation was associated with an increased risk of any DMC component (most vs. least: HR: 1.13; 95% CI: 1.05-1.22), especially diabetic kidney disease (HR: 1.14, 95% CI: 1.04-1.25) and neuropathy (HR: 1.31, 95% CI: 1.11-1.53). Any level of loneliness was associated with an increased risk of any DMC component (HR: 1.12; 95% CI: 1.02-1.23) and diabetic kidney disease (HR: 1.16, 95% CI: 1.03-1.30). Social isolation and loneliness exhibited associations with DMC comparable to other conventional risk factors including smoking, blood pressure, and physical activity. LIMITATIONS: Limited generalizability related to the composition of participants in the UK Biobank Study. CONCLUSIONS: Social isolation and loneliness were independently associated with a higher risk of incident DMC among individuals with T2DM, with comparable importance to other traditional risk factors. These findings underscore social isolation and loneliness as novel and potentially modifiable risk factors for DMC.

Localized, highly efficient secretion of signaling proteins by migrasomes.

Migrasomes, enriched with signaling molecules such as chemokines, cytokines and angiogenic factors, play a pivotal role in the spatially defined delivery of these molecules, influencing critical physiological processes including organ morphogenesis and angiogenesis. The mechanism governing the accumulation of signaling molecules in migrasomes has been elusive. In this study, we show that secretory proteins, including signaling proteins, are transported into migrasomes by secretory carriers via both the constitutive and regulated secretion pathways. During cell migration, a substantial portion of these carriers is redirected to the rear of the cell and actively transported into migrasomes, driven by the actin-dependent motor protein Myosin-5a. Once at the migrasomes, these carriers fuse with the migrasome membrane through SNARE-mediated mechanisms. Inhibiting migrasome formation significantly reduces secretion, suggesting migrasomes as a principal secretion route in migrating cells. Our findings reveal a specialized, highly localized secretion paradigm in migrating cells, conceptually paralleling the targeted neurotransmitter release observed in neuronal systems.

Swertiamarin relieves radiation-induced intestinal injury by limiting DNA damage.

Radiotherapy is the conventional treatment for pelvic abdominal tumors. However, it can cause some damage to the small intestine and colorectal, which are very sensitive to radiation. Radiation-induced intestinal injury (RIII) affects the prognosis of radiotherapy, causing sequelae of loss of function and long-term damage to patients' quality of life. Swertiamarin is a glycoside that has been reported to prevent a variety of diseases including but not limited to diabetes, hypertension, atherosclerosis, arthritis, malaria, and abdominal ulcers. However, its therapeutic effect and mechanism of action on RIII have not been established. We investigated whether swertiamarin has a protective effect against RIII. In this article, we use irradiator to create cellular and mouse models of radiation damage. Preventive administration of swertiamarin could reduce ROS and superoxide anion levels to mitigate the cellular damage caused by radiation. Swertiamarin also attenuated RIII in mice, as evidenced by longer survival, less weight loss and more complete intestinal barrier. We also found an increase in the relative abundance of primary bile acids in irradiated mice, which was reduced by both FXR agonists and swertiamarin, and a reduction in downstream interferon and inflammatory factors via the cGAS-STING pathway to reduce radiation-induced damage.

Critical role of the gut microbiota in immune responses and cancer immunotherapy.

The gut microbiota plays a critical role in the progression of human diseases, especially cancer. In recent decades, there has been accumulating evidence of the connections between the gut microbiota and cancer immunotherapy. Therefore, understanding the functional role of the gut microbiota in regulating immune responses to cancer immunotherapy is crucial for developing precision medicine. In this review, we extract insights from state-of-the-art research to decipher the complicated crosstalk among the gut microbiota, the systemic immune system, and immunotherapy in the context of cancer. Additionally, as the gut microbiota can account for immune-related adverse events, we discuss potential interventions to minimize these adverse effects and discuss the clinical application of five microbiota-targeted strategies that precisely increase the efficacy of cancer immunotherapy. Finally, as the gut microbiota holds promising potential as a target for precision cancer immunotherapeutics, we summarize current challenges and provide a general outlook on future directions in this field.

Mendelian randomization identifies causal effects of major depressive disorder on accelerated aging.

BACKGROUND: Evidence links major depressive disorder (MDD) with aging, but it's unclear if MDD accelerates aging and what factors mediate this transition. METHODS: Two-sample Mendelian randomization (MR) analyses were applied to estimate the causal association between MDD and frailty index (FI), telomere length (TL), and appendicular lean mass (ALM) from available genome-wide association studies in populations of European ancestry. Furthermore, we conducted mediation MR analyses to assess the mediating effects of 31 lifestyle factors or diseases on the causal relationship between MDD and aging. RESULTS: MDD was significantly causally associated with increased FI (ßIVW = 0.23, 95 % CI = 0.18 to 0.28, p = 1.20 × 10-17), shorter TL (ßIVW = -0.04, 95 % CI = -0.07 to -0.01, p = 0.01), and decreased ALM (ßIVW = -0.07, 95 % CI = -0.11 to -0.03, p = 3.54 × 10-4). The mediation analysis through two-step MR revealed smoking initiation (9.09 %), hypertension (6.67 %) and heart failure (5.36 %) mediated the causal effect of MDD on FI. Additionally, alcohol use disorders and alcohol dependence on the causal relationship between MDD and TL were found to be 17.52 % and 17.13 % respectively. LIMITATIONS: Confounding, statistical power, and Euro-centric focus limit generalization. CONCLUSION: Overall, individuals with MDD may be at a higher risk of experiencing premature aging, and this risk is partially influenced by the pathways involving smoking, alcohol use, and cardiovascular health. It underscores the importance of early intervention and comprehensive health management in individuals with MDD to promote healthy aging and overall well-being.

Homozygous variant in DRC3 (LRRC48) gene causes asthenozoospermia and male infertility.

Human infertility affects 10-15% of couples. Asthenozoospermia accounts for 18% of men with infertility and is a common male infertility phenotype. The nexin-dynein regulatory complex (N-DRC) is a large protein complex in the sperm flagellum that connects adjacent doublets of microtubules. Defects in the N-DRC can disrupt cilia/flagellum movement, resulting in primary ciliary dyskinesia and male infertility. Using whole-exome sequencing, we identified a pathological homozygous variant of the dynein regulatory complex subunit 3 (DRC3) gene, which expresses leucine-rich repeat-containing protein 48, a component of the N-DRC, in a patient with asthenozoospermia. The variant ENST00000313838.12: c.644dup (p. Glu216GlyfsTer36) causes premature translational arrest of DRC3, resulting in a dysfunctional DRC3 protein. The patient's semen count, color, and pH were normal according to the reference values of the World Health Organization guidelines; however, sperm motility and progressive motility were reduced. DRC3 protein was not detected in the patient's sperm and the ultrastructure of the patient's sperm flagella was destroyed. More importantly, the DRC3 variant reduced its interaction with other components of the N-DRC, including dynein regulatory complex subunits 1, 2, 4, 5, 7, and 8. Our data not only revealed the essential biological functions of DRC3 in sperm flagellum movement and structure but also provided a new basis for the clinical genetic diagnosis of male infertility.

Folic acid protects against isoniazid-induced liver injury via the m6A RNA methylation of cytochrome P450 2E1 in mice.

Background: Cytochrome P450 2E1 (CYP2E1) converts isoniazid (INH) to toxic metabolites and is critical in INH-induced liver injury. The aim is to investigate the effect of folic acid (FA) on CYP2E1 and INH-induced liver injury. Methods: Male Balb/c mice were used. The mice in the control group only received an AIN-93M diet. The AIN-93M diet was supplemented with 0.66 g INH/kg diet for the mice in the INH and FA groups. The mice in the FA group were treated with additional 0.01 g FA/kg diet. The one-carbon cycle metabolites, the expressions of CYP2E1 and the DNA and RNA methylation levels were detected to reveal the potential mechanism. Results: FA treatment significantly reduced the alanine aminotransferase level and alleviated the liver necrosis. The mRNA and protein expressions of CYP2E1 were significantly lower in the FA group than those in the INH group. The N6-methyladenosine RNA methylation level of Cyp2e1 significantly increased in the FA group compared with the INH group, while the DNA methylation levels of Cyp2e1 were similar between groups. Additionally, the liver S-adenosyl methionine (SAM)/S-adenosyl homocysteine (SAH) was elevated in the FA group and tended to be positively correlated with the RNA methylation level of Cyp2e1. Conclusion: FA alleviated INH-induced liver injury which was potentially attributed to its inhibitory effect on CYP2E1 expressions through enhancing liver SAM/SAH and RNA methylation.

Purification and Biochemical Characterization of a Novel Fibrinolytic Enzyme from Culture Supernatant of Coprinus comatus.

A novel fibrinolytic enzyme was produced by the liquid fermentation of Coprinus comatus. The enzyme was purified from the culture supernatant by hydrophobic interactions, gel filtration, and ion exchange chromatographies. It was purified by 241.02-fold, with a specific activity of 3619 U/mg and a final yield of 10.02%. SDS-PAGE analysis confirmed the purity of the enzyme, showing a single band with a molecular weight of 19.5 kDa. The first nine amino acids of the N-terminal of the purified enzyme were A-T-Y-T-G-G-S-Q-T. The enzyme exhibited optimal activity at a temperature of 42 °C and pH 7.6. Its activity was significantly improved by Zn2+, K+, Ca2+, Mn2+, and Mg2+ while being inhibited by Fe2+, Fe3+, Al2+, and Ba2+. The activity of the enzyme was completely inhibited by ethylenediamine tetraacetic acid (EDTA), and it was also dose-dependently inhibited by phenylmethylsulfonyl fluoride (PMSF) and soy trypsin inhibitor (SBTI). However, inhibitors such as N-α-tosyl-L-phenylalanine chloromethyl ketone (TPCK), aprotinin, and pepstatin did not significantly affect its activity, suggesting that the enzyme was a serine-like metalloproteinase. The enzyme acted as both a plasmin-like fibrinolytic enzyme and a plasminogen activator, and it also exhibited the capability to hydrolyze fibrinogen and fibrin. In vitro, it demonstrated the ability to dissolve blood clots and exhibit anticoagulant properties. Furthermore, it was found that the enzyme prolonged activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT), and reduced the levels of fibrinogen (FIB) and prothrombin activity (PA). Based on these studies, the enzyme has great potential to be developed as a natural agent for the prevention and treatment of thrombotic diseases.

The prognostic value of co-expression of stemness markers CD44 and CD133 in endometrial cancer.

Objective: The purpose of this study was to investigate the correlation between stemness markers (CD44 and CD133) and clinical pathological features, and to further explore the prognostic value of co-expression of CD44 & CD133 in endometrial cancer (EC). Methods: Clinical data of stage I-III EC patients who underwent initial surgical treatment at two large tertiary medical centers from 2015 to 2020 were retrospectively collected. Cohen's kappa coefficient was used to show the consistency of the expression between CD44 and CD133. The correlation between co-expression of CD44 & CD133 and prognosis of EC patients was explored using univariate and multivariate Cox regression analysis. Then, the prognosis models for early-stage (stage I-II) EC patients were constructed. Finally, stratified analysis was performed for EC patients in high-intermediate-risk and high-risk groups, Kaplan-Meier analysis was used to compare the survival differences between patients with and without adjuvant therapy in different co-expression states (low expression, mixed expression, high expression) of CD44 & CD133. Results: A total of 1168 EC patients were included in this study. The consistency of the expression between CD44 and CD133 was 70.5%, the kappa coefficient was 0.384. High expression of CD44 & CD133 was associated with early FIGO stage (P=0.017), superficial myometrial invasion (P=0.017), and negative lymphatic vessel space invasion (P=0.017). Cox regression analysis showed that the co-expression of CD44 & CD133 was significantly correlated with the prognosis of early-stage (stage I-II) patients (P=0.001 for recurrence and P=0.005 for death). Based on this, the nomogram models were successfully constructed to predict the prognosis of early-stage EC patients. Meanwhile, Kaplan-Meier analysis showed that patients with adjuvant therapy had a better overall prognosis than those without adjuvant therapy in high-intermediate-risk and high-risk groups. However, there was no statistically significant difference in survival between patients with and without adjuvant therapy in high expression of CD44 & CD133 group (P=0.681 for recurrence, P=0.621 for death). Conclusion: High expression of CD44 & CD133 was closely related to the adverse prognosis of early-stage EC patients. Meanwhile, patients with high expression of CD44 & CD133 may not be able to achieve significant survival benefits from adjuvant therapy.