Engineered exosomes with enhanced stability and delivery efficiency for glioblastoma therapy.

Due to the blood-brain barrier (BBB), the application of chemical drugs for glioblastoma treatment is severely limited. Recently, exosomes have been widely applied for drug delivery to the brain. However, the differences in brain targeting efficiency among exosomes derived from different cell sources, as well as the premature drug leakage during circulation, still limit the therapeutic efficacy. Here, we designed a functional oligopeptide-modified exosome loaded with doxorubicin (Pep2-Exos-DOX) for glioblastoma treatment. BV2 mouse microglial cell line was selected as the exosome source due to the favorable BBB penetration. To avoid drug release in the circulation, a redox-response oligopeptide was designed for incorporation into the membranes of exosomes to lock the drug during circulation. The enrichment of the drug in glioblastoma was confirmed. Pharmacodynamic evaluation showed Pep2-Exos-DOX possessed significant anti-cancer activity against glioblastoma as well as relative biosafety. This exosome-based drug delivery system modified with redox-response oligopeptides provides us a novel strategy for brain diseases treatment.

Effects of short-term florfenicol exposure on the gene expression pattern, midgut microbiota, and metabolome in the lepidopteran model silkworm (Bombyx mori).

Florfenicol (FF), an alternative veterinary antibiotic for chloramphenicol, has been widely utilized in livestock breeding to prevent and treat bacterial diseases. However, the toxicological effects of FF have yet to be fully disclosed. The domesticated silkworm (Bombyx mori), a lepidopteran model, was selected to assess the toxicological effects of FF dietary exposure with multi-omics. The findings showed that high-dose (250 µg/L) FF exposure increased the whole cocoon weight. High-dose FF exposure affected the species richness and community diversity of the microbiota in the silkworm midgut. Biochemical processes and innate immunity were impacted by FF exposure. The KEGG pathways impacted by the midgut microbiota and their metabolites were compared, and several pathways were found to be related to the two ecosystems. In addition, the innate immunity and lipid metabolism pathways were impacted, and some of the differentially expressed genes were enriched in these pathways. These related pathways may involve crosstalk between the midgut microbiota shift, midgut biological functions, and global gene expression. Therefore, our study also advances the application of the silkworm larval model in assessing antibiotic metabolic toxicity and provides novel insights into the potential risks of FF.

Heuristic Path Search and Multi-Attribute Decision-Making-Based Routing Method for Vehicular Safety Messages.

Efficient routing in urban vehicular networks is essential for timely and reliable safety message transmission, and the selection of paths and relays greatly affects the quality of routing. However, existing routing methods usually face difficulty in finding the globally optimal transmission path due to their greedy search strategies or the lack of effective ways to accurately evaluate relay performance in intricate traffic scenarios. Therefore, we present a vehicular safety message routing method based on heuristic path search and multi-attribute decision-making (HMDR). Initially, HMDR utilizes a heuristic path search, focusing on road section connectivity, to pinpoint the most favorable routing path. Subsequently, it employs a multi-attribute decision-making (MADM) technique to evaluate candidate relay performance. The subjective and objective weights of the candidate relays are determined using ordinal relationship analysis and the Criteria Importance Through Intercriteria Correlation (CRITIC) weighting methods, respectively. Finally, the comprehensive utility values of the candidate relays are calculated in combination with the link time and the optimal relay is selected. In summary, the proposed HMDR method is capable of selecting the globally optimal transmission path, and it comprehensively considers multiple metrics and their relationships when evaluating relays, which is conducive to finding the optimal relay. The experimental results show that even if the path length is long, the proposed HMDR method gives preference to the path with better connectivity, resulting in a shorter total transmission delay for safety messages; in addition, HMDR demonstrates faster propagation speed than the other evaluated methods while ensuring better one-hop distance and one-hop delay. Therefore, it helps to improve the performance of vehicular safety message transmission in intricate traffic scenarios, thus providing timely data support for secure driving.

Technology Trends for Massive MIMO towards 6G.

At the dawn of the next-generation wireless systems and networks, massive multiple-input multiple-output (MIMO) in combination with leading-edge technologies, methodologies, and architectures are poised to be a cornerstone technology. Capitalizing on its successful integration and scalability within 5G and beyond, massive MIMO has proven its merits and adaptability. Notably, a series of evolutionary advancements and revolutionary trends have begun to materialize in recent years, envisioned to redefine the landscape of future 6G wireless systems and networks. In particular, the capabilities and performance of future massive MIMO systems will be amplified through the incorporation of cutting-edge technologies, structures, and strategies. These include intelligent omni-surfaces (IOSs)/intelligent reflecting surfaces (IRSs), artificial intelligence (AI), Terahertz (THz) communications, and cell-free architectures. In addition, an array of diverse applications built on the foundation of massive MIMO will continue to proliferate and thrive. These encompass wireless localization and sensing, vehicular communications, non-terrestrial communications, remote sensing, and inter-planetary communications, among others.

The effects of short-term dietary exposure to SiO2 nanoparticle on the domesticated lepidopteran insect model silkworm (Bombyx mori): Evidence from the perspective of multi-omics.

Silicon dioxide nanoparticles (nSiO2) are one of the widely utilized nanoparticle (NPSs) materials, and exposure to nSiO2 is ubiquitous. With the increasing commercialization of nSiO2, the potential risk of nSiO2 release to the health and the ecological environment have been attracted more attention. In this study, the domesticated lepidopteran insect model silkworm (Bombyx mori) was utilized to evaluate the biological effects of dietary exposure to nSiO2. Histological investigations showed that nSiO2 exposure resulted in midgut tissue injury in a dose-dependent manner. Larval body mass and cocoon production were reduced by nSiO2 exposure. ROS burst was not triggered, and the activities of antioxidant enzymes were induced in the midgut of silkworm exposure to nSiO2. RNA-sequencing revealed that the differentially expressed genes induced by nSiO2 exposure were predominantly enriched into xenobiotics biodegradation and metabolism, lipid, and amino acid metabolism pathways. 16 S rDNA sequencing revealed that nSiO2 exposure altered the microbial diversity in the gut of the silkworm. Metabolomics analysis showed that the combined uni- and multivariate analysis identified 28 significant differential metabolites from the OPLS-DA model. These significant differential metabolites were predominantly enriched into the metabolic pathways, including purine metabolism and tyrosine metabolism and so. Spearman correlation analysis and the Sankey diagram established the relationship between microbe and metabolites, and some genera may play crucial and pleiotropic functions in the interaction between microbiome and host. These findings indicated that nSiO2 exposure could impact the dysregulation of genes related to xenobiotics metabolism, gut dysbiosis, and metabolic pathways and provided a valuable reference for assessing nSiO2 toxicity from a multi-dimensional perspective.

Clinical Analysis of Macular Choroidal Thickness in Pseudoexfoliative Glaucoma and Primary Open-Angle Glaucoma.

PURPOSE: To evaluate the differences in macular choroidal thickness and volume among patients with pseudoexfoliative glaucoma (PXG), patients with primary open-angle glaucoma (POAG), and controls. METHODS: A total of 50 PXG patients (50 eyes) and 56 POAG patients (56 eyes) were selected as the PXG group and the POAG group, respectively, in this case-control study. A total of 54 age-, gender-, IOP-, and axial length-matched healthy individuals (54 eyes) were selected as the control group. Enhanced-depth imaging-optical coherence tomography (EDI-OCT) was used to measure and analyze the choroidal thicknesses and volumes in 9 macular regions of all subjects. RESULTS: The choroidal thicknesses in the central subfield (CSM), temporal inner macula (TIM), inferior inner macula (IIM), and temporal outer macula (TOM) and the mean macular choroidal thickness were significantly thinner in the PXG group than in the control group (all P < 0.05). The choroidal volumes in the TIM, IIM, and TOM and the mean macular choroidal volume were significantly smaller in the PXG group than in the control group (all P < 0.05). The choroidal thicknesses in the CSM and IIM and the mean macular choroidal thickness were significantly thinner in the PXG group than in the POAG group (all P < 0.05). The choroidal volumes in the IIM and TOM and the mean macular choroidal volume were significantly smaller in the PXG group than in the POAG group (all P < 0.05). Multivariable linear regression analysis showed that the mean macular choroidal thickness was significantly thinner in association with older subjects and longer axial length eyes. There was no association between the macular choroidal thickness of various macular regions and visual field mean defect (MD) in groups PXG and POAG (all P > 0.05). CONCLUSIONS: The macular choroidal thicknesses and volumes (inferior and temporal) in PXG patients were thinner and smaller than those in POAG patients and healthy individuals. The role of choroidal thickness changes in the course of PXG remains unclear. A future prospective study is needed to better define these changes in PXG patients.

Clinical observation of macular choroidal thickness in primary chronic angle-closure glaucoma.

PURPOSE: To comparatively analyze differences in macular choroidal thickness and volume in primary chronic angle-closure glaucoma (PACG) eyes. METHODS: Thirty-one PACG patients were sequentially selected for this case-control study. Thirty-one eyes with PACG were included in group A, 31 fellow eyes were included in group B, and group C included 67 normal eyes. Enhanced-depth imaging optical coherence tomography (EDI-OCT) was used to measure choroidal thickness and volume. RESULTS: The choroidal thicknesses and volumes of the central subfield macula (CSM), nasal inner macula (NIM), temporal inner macula (TIM), inferior inner macula (IIM), temporal outer macula (TOM), inferior outer macula (IOM), and mean macula (MM) in group A were all higher than those in group C (P < 0.05). The choroidal thicknesses and volumes of the NIM, superior inner macula (SIM), IIM, nasal outer macula (NOM), and MM in group B were all higher than those in group C (P < 0.05). No statistically significant differences were found between groups A and B (P > 0.05). The choroidal thicknesses of different macular regions in group A were not correlated with the mean defect (MD). CONCLUSION: Increased macular choroidal thickness may be a common anatomical characteristic of PACD eyes. Macular choroidal thickness is not a good marker for assessing PACG severity.

Correlation Analysis between Macular Choroidal Thickness and Visual Field Mean Defect in Primary Open-Angle Glaucoma.

PURPOSE: To evaluate the differences in macular choroidal thickness and volume between patients with primary open-angle glaucoma (POAG) and healthy controls to assess the correlation between macular choroidal thickness and visual field mean defect (MD). METHODS: Case-control study. A total of 101 patients (101 eyes) with POAG who were hospitalized in our hospital and 102 healthy subjects (102 eyes) matched by age, sex, and axial length were consecutively selected as the POAG group and the control group, respectively. The macular choroidal thickness and volume in nine regions were measured in all subjects by enhanced-depth imaging optical coherence tomography (EDI-OCT). RESULTS: The mean thicknesses of the choroid in the macular area in the POAG group and healthy group were 207.97 ± 62.83 µm and 208.24 ± 47.97 µm, and the mean volumes were 0.63 ± 0.19 µm3 and 0.64 ± 0.14 µm3. There were no significant differences in macular choroidal thickness, volumes of various macular regions, or mean choroidal thickness or volume between the POAG and healthy groups (all p > 0.05). The macular choroidal thickness of various macular regions was not correlated with visual field MD in the POAG group (all p > 0.05). CONCLUSION: The macular choroidal thicknesses and volumes in POAG patients were not significantly different from those in healthy individuals. The macular choroidal thickness was not correlated with MD in POAG patients. Therefore, macular choroidal thickness is not an appropriate parameter to evaluate damage caused by POAG, and the role of the macular choroid thickness in POAG needs to be further investigated.