In Situ Sprayed Exosome-Cross-Linked Gel as Artificial Lymph Nodes for Postoperative Glioblastoma Immunotherapy.

One key challenge in postoperative glioblastoma immunotherapy is to guarantee a potent and durable T-cell response, which is restricted by the immunosuppressive microenvironment within the lymph nodes (LNs). Here, we develop an in situ sprayed exosome-cross-linked gel that acts as an artificial LN structure to directly activate the tumor-infiltrating T cells for prevention of glioma recurrence. Briefly, this gel is generated by a bio-orthogonal reaction between azide-modified chimeric exosomes and alkyne-modified alginate polymers. Particularly, these chimeric exosomes are generated from dendritic cell (DC)-tumor hybrid cells, allowing for direct and robust T-cell activation. The gel structure with chimeric exosomes as cross-linking points avoids the quick clearance by the immune system and thus prolongs the durability of antitumor T-cell immunity. Importantly, this exosome-containing immunotherapeutic gel provides chances for ameliorating functions of antigen-presenting cells (APCs) through accommodating different intracellular-acting adjuvants, such as stimulator of interferon genes (STING) agonists. This further enhances the antitumor T-cell response, resulting in the almost complete elimination of residual lesions after surgery. Our findings provide a promising strategy for postsurgical glioma immunotherapy that warrants further exploration in the clinical arena.

Stress response of Microcystis aeruginosa to chlorine during transportation: The significance of surface-adsorbed organic matter.

The desorption of surface-adsorbed organic matter (S-AOM) without damaging algal cells was reported to be the key to destabilizing Microcystis aeruginosa (M. aeruginosa) cells while avoiding intracellular organic matter (IOM) release in our previous study. However, a temporal effect was found from spontaneous and continuous damage to algal cells even after quenching. This study aims to demonstrate the mechanism of the temporal inactivation effect and the stress response exhibited by chlorine-oxidized algal cells, and finally guide the prechlorination process for algae-laden water at water sources. Chlorine was proved to cause oxidative stress to M. aeruginosa cells, and result in a rapid increase in intracellular reactive oxygen species (ROS) levels. S-AOM appeared to have a protective effect on algal cells against oxidative damage, as evidenced by the maintenance of algal cell integrity and activated antioxidant enzymes. In addition, the activity of Caspase 3, a key protease for the execution of programmed cell death (PCD), was significantly enhanced during prechlorination. Cellular chromatin condensation and DNA fragmentation occurred in the early stages of PCD in algal cells. Therefore, the pre-treatment of algae-laden water at water sources, even with low chlorine doses, can induce a risk of significant algal cell death during the water transfer process due to activation of the PCD process, resulting in a higher health risk for drinking water. These findings indicate that both the dosage of chlorine and the duration of the transportation process should be considered during the prechlorination of algae-laden water, which can provide an important basis for avoiding increasing the risk to drinking water safety.

Diagnostic efficacy of tract-specific diffusion tensor imaging in cervical spondylotic myelopathy with electrophysiological examination validation.

PURPOSE: This study aimed to investigate the effectiveness of tract-specific diffusion tensor imaging (DTI) metrics in identifying the responsible segments for neurological dysfunction in cervical spondylotic myelopathy (CSM). METHODS: The study encompassed nineteen participants diagnosed with CSM, including 10 males and 9 females. Additionally, a control group consisting of ten healthy caregivers (5 males and 5 females) were recruited with no symptoms and no compressions on magnetic resonance imaging (MRI). All participants underwent a comprehensive physical examination, MRI assessment, and DTI examination conducted by a senior chief physician. Several parameters were collected from the MR images, including the aspect ratio (defined as the anteroposterior diameter / the transverse diameter of the corresponding segment's spinal cord), transverse ratio (defined as the transverse diameter of the corresponding segment's spinal cord / the transverse diameter of the spinal cord at C2/3), and T2 high signal of the spinal cord. Furthermore, quantitative DTI metrics, such as axial diffusivity (AD), mean diffusivity (MD), radial diffusivity (RD), and fractional anisotropy (FA), were calculated using automatic region-of-interest (ROI) analysis for both whole spinal cord column and dorsal column. Receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic efficacy of the aspect ratio, transverse ratio, and DTI parameters. The area under the curve (AUC), sensitivity, and specificity were calculated. Intraoperative spinal cord electrophysiological examination was performed as the objective measure of spinal cord function during surgery. RESULTS: As determined by electrophysiological examination, neurological dysfunction was found in 2 patients due to C3/4 compression, in 10 patients due to C4/5 compression, in 6 patients due to C5/6 compression, and in 1 patient due to C6/7 compression. The modified Japanese Orthopedic Association scale (mJOA) was 12.71 ± 1.55 in the CSM group, with 4.87 ± 0.72 for sensory nerve function and 5.05 ± 1.35 for motor nerve function. For the control group, none of the volunteers had neurological dysfunction. T2 high signal was found at the most stenotic segment in 13 patients of the CSM group. Considering all the cervical segments, the aspect ratio (AUC = 0.823, P = 0.001, Sensitivity = 68.42%, Specificity = 82.47%) was more capable of determining the responsible segment than transverse ratio (AUC = 0.661, P = 0.027, Sensitivity = 68.42%, Specificity = 67.01%). AD, MD, and RD were significantly higher while FA was significantly lower in the responsible segment than in the irresponsible segment (P < 0.05). The AUC of DTI-Dorsal column parameters (AD, MD, RD, FA) was larger than the corresponding parameters of the DTI (Whole spinal cord). AD of DTI-Dorsal Column possessed the greatest efficacy (AUC = 0.823, sensitivity = 84.21%, specificity = 77.32%) to determine the responsible segment, larger than AD of DTI-Whole spinal cord (AUC = 0.822, P = 0.001, Sensitivity = 89.47%, Specificity = 77.32%), aspect ratio (AUC = 0.823, P = 0.001, Sensitivity = 68.42%, Specificity = 82.47%) and transverse ratio (AUC = 0.661, P = 0.027, Sensitivity = 68.42%, Specificity = 67.01%). Subgroup analysis revealed that the diagnostic efficacy of DTI and MRI parameters was influenced by cervical spine segment. CONCLUSIONS: When considering all cervical segments, AD from the DTI-Dorsal Column exhibited the most significant potential in identifying responsible segments. This potential was found to be superior to that of DTI-Whole spinal cord, aspect ratio, the most stenotic segment, T2 high signals, transverse ratio, motor nerve dysfunction, and sensory nerve dysfunction. The diagnostic effectiveness of both DTI and MRI parameters was notably influenced by the specific cervical spine segment.