In situ implantable DNA hydrogel for diagnosis and therapy of postoperative rehemorrhage following intracerebral hemorrhage surgery.

Postoperative rehemorrhage following intracerebral hemorrhage surgery is intricately associated with a high mortality rate, yet there is now no effective clinical treatment. In this study, we developed a hemoglobin (Hb)-responsive in situ implantable DNA hydrogel comprising Hb aptamers cross-linked with two complementary chains and encapsulating deferoxamine mesylate (DFO). Functionally, the hydrogel generates signals upon postoperative rehemorrhage by capturing Hb, demonstrating a distinctive "self-diagnosis" capability. In addition, the ongoing capture of Hb mediates the gradual disintegration of the hydrogel, enabling the on-demand release of DFO without compromising physiological iron-dependent functions. This process achieves self-treatment by inhibiting the ferroptosis of neurocytes. In a collagenase and autologous blood injection model-induced mimic postoperative rehemorrhage model, the hydrogel exhibited a 5.58-fold increase in iron absorption efficiency, reducing hematoma size significantly (from 8.674 to 4.768 cubic millimeters). This innovative Hb-responsive DNA hydrogel not only offers a therapeutic intervention for postoperative rehemorrhage but also provides self-diagnosis feedback, holding notable promise for enhancing clinical outcomes.

Regulation of cancer cell ferroptosis by PTRF/Cavin-1.

Ovarian cancer, marked by high rate of recurrence, novel therapeutic strategies are needed to improve patient outcome. One of the potential strategies is inducing ferroptosis in ovarian cancer cells. Ferroptosis is an iron-dependent, lipid peroxidation-driven mode of cell death primarily occurring on the cell membrane. PTRF, an integral component of the caveolae structures located on the cell membrane, is involved in a multitude of physiological processes, including but not limited to, endocytosis, signal transduction, and lipid metabolism. This study elucidates the relationship between PTRF and ferroptosis in ovarian cancer, offering a fresh perspective for the development of new therapeutic strategies. We knocked down PTRF employing siRNA in the ovarian cancer cell lines HEY and SKOV3, following which we stimulated ferroptosis with Erastin (Era). Our research indicates that the lack of PTRF sensitizes cancer cells to ferroptosis, likely by altering membrane stability and tension, thereby affecting signal pathways related to ferroptosis, such as lipid and atherosclerosis, fluid shear stress, and atherosclerosis. Our findings provide new insights for developing new treatments for ovarian cancer.

A Variable Stiffness Bioinspired Swallowing Gripper Based on Particle Jamming.

As the chameleon tongue swallows the food, it wraps the entrapped meat around the food, ensuring that it is completely enclosed and preventing it from falling off. Inspired by swallow behavior, this article introduces the design, manufacture, modeling, and experimentation of a variable stiffness swallowing gripper (VSSG). The VSSG is comprised of an intimal membrane, an adventitial membrane, and an internal medium of particles and liquid water. This gripper integrates swallowing behavior with a particle jamming mechanism, exhibiting both soft and rigid state. In the soft state, it gently swallows objects by folding its intimal and adventitial membranes. In the rigid state, the bearing capacity is enhanced by promoting particle jamming phenomenon through pumping out liquid water. Therefore, the proposed gripper has the capability to mitigate the issue of extrusion force applied on the object, while simultaneously enhancing the load-bearing capacity of swallowing gripper. In this article, the swallowing principle of the VSSG is analyzed, the mathematical model of the holding force and extrusion force is deduced, and preliminary experiments are carried out to verify the actual gripping effect of the gripper. The experimental results demonstrate that the VSSG can successfully swallow objects of different shapes in the soft state, exhibiting excellent flexibility and adaptability. The carrying capacity of the gripper in the rigid state increased approximately twofold compared with its soft state. In addition, several swallowing grippers with different filling medium were comparatively studied, and the results show that the VSSG has a large load-bearing capability.

Preoperative prediction of microvascular invasion classification in hepatocellular carcinoma based on clinical features and MRI parameters.

Microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is a critical pathological factor and the degree of MVI influences treatment decisions and patient prognosis. The present study aimed to predict the MVI classification based on preoperative MRI features and clinical parameters. The present retrospective cohort study included 150 patients (training cohort, n=108; validation cohort, n=42) with pathologically confirmed HCC. Clinical and imaging characteristics data were collected from Shengli Oilfield Central Hospital (Dongying, China). Univariate and multivariate logistic regression analyses were conducted to assess the association of clinical variables and MRI parameters with MVI (grade M1 and M2) and the M2 classification. Nomograms were developed based on the predictive factors of MVI and the M2 classification. The discrimination capability, calibration and clinical usefulness of the nomograms were evaluated. Multivariate analysis revealed an association between the Lens culinaris agglutinin-reactive fraction of α-fetoprotein, protein induced by vitamin K absence-II and tumor margin and MVI-positive status, while peritumoral enhancement and tumor size were demonstrated to be marginal predictors, but were also included in the nomogram. However, among MVI-positive patients, only peritumoral hypointensity and tumor size were demonstrated to be risk factors for the M2 classification. The nomograms, incorporating these variables, exhibited a strong ability to discriminate between MVI-positive and MVI-negative patients with HCC in both the training and validation cohort [area under the curve (AUC), 0.877 and 0.914, respectively] and good performance in predicting the M2 classification in the training and validation cohorts (AUC, 0.720 and 0.782, respectively). Nomograms incorporating clinical parameters and preoperative MRI features demonstrated promising potential as straightforward and effective tools for predicting MVI and the M2 classification in patients with HCC. Such predictive tools could aid in the judicious selection of optimal clinical treatments.

Role of the Clinical Features and MRI Parameters on Ki-67 Expression in Hepatocellular Carcinoma Patients: Development of a Predictive Nomogram.

PURPOSE: To develop a nomogram using clinical features and the MRI parameters for preoperatively predicting the expression of Ki-67 in patients with hepatocellular carcinoma (HCC). METHODS: One hundred and forty patients (training cohorts: n = 108; validation cohorts: n = 32) with confirmed HCC were investigated. Mann-Whitney U test, independent sample t-test, and chi-squared test were used to analyze the continuous and categorical variables. Univariate and multivariate logistic regression analyses were performed to examine the clinical variables and parameters from MRI associated with Ki-67 expression. As a result, a nomogram was developed based on these associations in patients with HCC. The performance of the nomogram was evaluated using the area under the receiver operating characteristic curve (AUC) and calibration curves. RESULTS: In the training set, multivariable logistic regression analysis revealed that lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) levels, protein induced by vitamin K absence or antagonist-II (PIVKA-II) levels, and tumor shape were independent predictors for Ki-67 expression (p < 0.05). These three variables and the apparent diffusion coefficient (ADC) value were used to establish a nomogram, while the ADC value was found to be a marginal significant predictor. The model demonstrated a strong ability to discriminate Ki-67 expression in both the training and validation cohorts (AUC = 0.862, 0.877). CONCLUSION: A non-invasive preoperative prediction method, which incorporates MRI variables and clinical features was developed, and showed effectiveness in evaluating Ki-67 expression in HCC patients.

Neutrophil hitchhiking nanoparticles enhance bacteria-mediated cancer therapy via NETosis reprogramming.

Bacteria have shown great potential in anti-tumor treatment, and an attenuated strain of Salmonella named VNP20009 has been shown to be safe in clinical trials. However, colonized bacteria recruit neutrophils into the tumor, which release NETs to capture and eliminate bacteria, compromising bacterial-based tumor treatment. In this study, we report a neutrophil hitchhiking nanoparticles (SPPS) that block the formation of NET to enhance bacteria-mediated tumor therapy. In the 4 T1 tumor-bearing mouse model, following 24 h of bacterial therapy, there was an approximately 3.0-fold increase in the number of neutrophils in the bloodstream, while the amount of SPPS homing to tumor tissue through neutrophil hitchhiking increased approximately 2.0-fold. It is worth noting that the NETs in tumors significantly decreased by approximately 2.0-fold through an intracellular ROS scavenging-mediated NETosis reprogramming, thereby increasing bacterial vitality by 1.9-fold in tumors. More importantly, the gene drug (siBcl-2) loaded in SPPS can be re-encapsulated in apoptotic bodies by reprogramming neutrophils from NETosis to apoptosis, and enable the redelivery of drugs to tumor cells, further boosting the antitumor efficacy with a synergistic effect, resulting in about 98% tumor inhibition rate and 90% survival rate.

Toxicological impacts of microplastics on virulence, reproduction and physiological process of entomopathogenic nematodes.

Microplastics have emerged as significant and concerning pollutants within soil ecosystems. Among the soil biota, entomopathogenic nematodes (EPNs) are lethal parasites of arthropods, and are considered among the most effective biological agents against pests. Infective juveniles (IJs) of EPNs, as they navigate the soil matrix scavenging for arthropod hosts to infect, they could potentially encounter microplastics. Howver, the impact of microplastics on EPNs has not been fully elucidated yet. We addressed this gap by subjecting Steinernema feltiae EPNs to polystyrene microplastics (PS-MPs) with various sizes, concentrations, and exposure durations. After confirming PS-MP ingestion by S. feltiae using fluorescent dyes, we found that the PS-MPs reduced the survival, reproduction, and pathogenicity of the tested EPNs, with effects intensifying for smaller PS-MPs (0.1-1 µm) at higher concentrations (105 µg/L). Furthermore, exposure to PS-MPs triggered oxidative stress in S. feltiae, leading to increased reactive oxygen species levels, compromised mitochondrial membrane potential, and increased antioxidative enzyme activity. Furthermore, transcriptome analyses revealed PS-MP-induced suppression of mitochondrial function and oxidative phosphorylation pathways. In conclusion, we show that ingestion of PS-MPs by EPNs can compromise their fitness, due to multple toxicity effects. Our results bear far-reaching consequences, as the presence of microplastics in soil ecosystems could undermine the ecological role of EPNs in regulating pest populations.