Structure-Guided Design of Ferritin-Platinum Prodrugs for Targeted Therapy of Esophageal Squamous Cell Carcinoma.

Due to its intrinsic tumor-targeting attribute, limited immunogenicity, and cage architecture, ferritin emerges as a highly promising nanocarrier for targeted drug delivery. In the effort to develop ferritin cage-encapsulated cisplatin (CDDP) as a therapeutic agent, we found unexpectedly that the encapsulation led to inactivation of the drug. Guided by the structural information, we deciphered the interactions between ferritin cages and CDDP, and we proposed a potential mechanism responsible for attenuating the antitumor efficacy of CDDP encapsulated within the cage. Six platinum prodrugs were then designed to avoid the inactivation. The antitumor activities of these ferritin-platinum prodrug complexes were then evaluated in cells of esophageal squamous cell carcinoma (ESCC). Compared with free CDDP, the complexes were more effective in delivering and retaining platinum in the cells, leading to increased DNA damage and enhanced cytotoxic action. They also exhibited improved pharmacokinetics and stronger antitumor activities in mice bearing ESCC cell-derived xenografts as well as patient-derived xenografts. The successful encapsulation also illustrates the critical significance of comprehending the interactions between small molecular drugs and ferritin cages for the development of precision-engineered nanocarriers.

Substantial removal of four pesticide residues in three fruits with ozone microbubbles.

Developing a straightforward method to remove pesticide residues from fruits is essential for food safety. In this study, ozone microbubble treatment was performed on three fruits (strawberry, cherry, and apricot) to remove four pesticide residues (emamectin benzoate, azoxystrobin, boscalid, and difenoconazole) while comparing removal efficiency. The concentration of hydroxyl radicals in different washing orientations was homogeneous at a concentration ranging between 8.9 and 10.2 µmol·L-1. Under long washing time (18 min), strawberry, cherry, and apricot obtained higher removal rates of 51 %∼65 %, 51 %∼59 % and 24 %∼70 %, respectively. Moreover, scanning electron microscopy (SEM) and contact angle (CA) revealed that apricot has better hydrophobicity, leading to a higher pesticide removal of 45 âˆ¼ 84 % with less water and more vigorous washing. Notably, vitamin C content in fruits remain largely unchanged following ozone microbubble treatment. This study demonstrated the effectiveness of ozone microbubble treatment as pollution-free method for enhancing food safety by removing pesticide residues on fruits.

Analysis of the association between serum levels of 25(OH)D, retinol binding protein, and Cyclooxygenase-2 and the disease severity in patients with diabetic foot ulcers.

Diabetic foot ulcers (DFUs) pose significant clinical challenges, representing severe complications in diabetes mellitus patients and contributing to non-traumatic amputations. Identifying reliable biomarkers can optimize early diagnosis and improve therapeutic outcomes. This study focused on evaluating the association between serum levels of 25-hydroxyvitamin D [25-(OH)D], Serum Retinol Binding Protein (RBP), and Cyclooxygenase-2 (COX-2) in elderly DFU patients. A retrospective study involving 240 participants, from March 2020 to March 2023. The participants were segmented into three cohorts: 80 with DFUs, 80 diabetic patients without DFUs, and 80 healthy controls. Serum concentrations of the three biomarkers were assayed using methods like enzyme-linked immunosorbent assay (ELISA), chemiluminescence immunoassay, and an automated biochemistry analyser. Comparisons were made both between groups and within the DFU group based on disease severity. Statistical analysis revealed significant differences in biomarker levels across the groups (p < 0.05). COX-2 and RBP concentrations were highest in the DFU group, followed by the non-DFU diabetic group, and lowest in the control group. Conversely, 25(OH)D levels were highest in the control group, followed by the non-DFU diabetic group, and lowest in the DFU group. Within the DFU group, RBP and COX-2 levels increased with disease severity, while 25(OH)D levels decreased. These variations were especially pronounced in patients with the most severe Wagner grading. A significant positive correlation was observed between disease severity and levels of RBP (r = 0.651, p < 0.05) and COX-2 (r = 0.356, p < 0.05). Conversely, a significant negative correlation was identified between disease severity and 25(OH)D levels (r = -0.658, p < 0.05). Assessing 25(OH)D, RBP, and COX-2 serum levels offers a promising tool for evaluating the severity and progression of DFUs. Monitoring these biomarkers can enrich our understanding of the metabolic and inflammatory pathways of the disease and potentially refine therapeutic strategies.

Hemodynamic analysis of unilateral and bilateral renal artery stenosis based on fluid-structure interaction.

Renal artery stenosis (RAS) hypertension is a common type of secondary hypertension. This paper aimed to explore how unilateral renal artery stenosis (Uni-RAS) and bilateral renal artery stenosis (Bi-RAS) caused renovascular hypertension with the fluid-structure interaction (FSI) method. Based on a real RAS model, 20 ideal models with different stenosis degrees were established by modifying the stenosis segment. The hemodynamic parameters at different degrees of stenosis, mass flow rate (MFR), pressure drop (PD), fractional flow reserve (FFR), oscillatory shear index (OSI), and relative residence time (RRT), were numerically calculated by the computational fluid dynamics (CFD) method. The numerical results showed that RAS caused the decrease of MFR, and the increase of PD and the proportion of high OSI and high RRT. In the case of RAS, it could not be regarded as a reference indicator for causing renovascular hypertension that the value of FFR was greater than 0.9. In addition, the results of the statistical analysis indicated that Uni-RAS and Bi-RAS were statistically different for MFR, PD and the proportion of high RRT.

CD146 promotes malignant progression of breast phyllodes tumor through suppressing DCBLD2 degradation and activating the AKT pathway.

BACKGROUND: As a rapid-progressing tumor, breast malignant phyllodes tumors (PTs) are challenged by the lack of effective therapeutic strategies and suitable prognostic markers. This study aimed to clarify the role and mechanism of CD146 on promoting PTs malignant progression, and to identify a novel prognosis marker and treatment target of breast malignant PTs. METHODS: The expression and prognostic significance of CD146 in PTs was detected through single-cell RNA-sequencing (scRNA-seq), immunostaining, real-time PCR and other methodologies. Functional experiments including proliferation assay, colony formation assay, transwell assay, and collagen contraction assay were conducted to validate the role of CD146 in malignant progression of PTs. The efficacy of anti-CD146 monoclonal antibody AA98 against malignant PTs was corroborated by a malignant PT organoid model and a PT patient-derived xenograft (PDX) model. Transcriptome sequencing, proteomic analysis, co-immunoprecipitation, and pull-down assay was employed to identify the modulating pathway and additional molecular mechanism. RESULTS: In this study, the scRNA-seq analysis of PTs disclosed a CD146-positive characteristic in the α-SMA+ fibroblast subset. Furthermore, a progressive elevation in the level of CD146 was observed with the malignant progression of PTs. More importantly, CD146 was found to serve as an independent predictor for recurrence in PT patients. Furthermore, CD146 was found to augment the viability and invasion of PTs. Mechanistically, CD146 acted as a protective "shield" to prevent the degradation of Discoidin, CUB, and LCCL domain-containing protein 2 (DCBLD2), thereby activating the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway and enhancing malignant behaviors of PT cells. In the malignant PT organoid and PDX model, a significant suppression of malignant PT growth was observed after the application of AA98. CONCLUSIONS: These findings suggested that CD146 served as an efficacious marker for predicting PT malignant progression and showed promise as a prognosis marker and treatment target of breast malignant PTs. The study further unveiled the essential role of the CD146-DCBLD2/PI3K/AKT axis in the malignant progression of PTs.

Reactive oxidative species (ROS)-based nanomedicine for BBB crossing and glioma treatment: current status and future directions.

Glioma is the most common primary intracranial tumor in adults with poor prognosis. Current clinical treatment for glioma includes surgical resection along with chemoradiotherapy. However, the therapeutic efficacy is still unsatisfactory. The invasive nature of the glioma makes it impossible to completely resect it. The presence of blood-brain barrier (BBB) blocks chemotherapeutic drugs access to brain parenchyma for glioma treatment. Besides, tumor heterogeneity and hypoxic tumor microenvironment remarkably limit the efficacy of radiotherapy. With rapid advances of nanotechnology, the emergence of a new treatment approach, namely, reactive oxygen species (ROS)-based nanotherapy, provides an effective approach for eliminating glioma via generating large amounts of ROS in glioma cells. In addition, the emerging nanotechnology also provides BBB-crossing strategies, which allows effective ROS-based nanotherapy of glioma. In this review, we summarized ROS-based nanomedicine and their application in glioma treatment, including photodynamic therapy (PDT), photothermal therapy (PTT), chemodynamic therapy (CDT), sonodynamic therapy (SDT), radiation therapy, etc. Moreover, the current challenges and future prospects of ROS-based nanomedicine are also elucidated with the intention to accelerate its clinical translation.

A subpopulation of CD146+ macrophages enhances antitumor immunity by activating the NLRP3 inflammasome.

As one of the main tumor-infiltrating immune cell types, tumor-associated macrophages (TAMs) determine the efficacy of immunotherapy. However, limited knowledge about their phenotypically and functionally heterogeneous nature restricts their application in tumor immunotherapy. In this study, we identified a subpopulation of CD146+ TAMs that exerted antitumor activity in both human samples and animal models. CD146 expression in TAMs was negatively controlled by STAT3 signaling. Reducing this population of TAMs promoted tumor development by facilitating myeloid-derived suppressor cell recruitment via activation of JNK signaling. Interestingly, CD146 was involved in the NLRP3 inflammasome-mediated activation of macrophages in the tumor microenvironment, partially by inhibiting transmembrane protein 176B (TMEM176B), an immunoregulatory cation channel. Treatment with a TMEM176B inhibitor enhanced the antitumor activity of CD146+ TAMs. These data reveal a crucial antitumor role of CD146+ TAMs and highlight the promising immunotherapeutic approach of inhibiting CD146 and TMEM176B.

BGCP-based traffic data imputation and accident detection applications for the national trunk highway.

Facing the currently large quantity of intelligent transportation data, missing ones is often inevitable. Some previous works have shown the advantages of tensor decomposition-based approaches in solving multi-dimensional data imputation problems. However, a research gap still exists in examining the effect of applying these methods on imputation performance and their application to accident detection. Thus, referring to a two-month spatiotemporal traffic speed dataset, collected on the national trunk highway in Shandong, China, this paper employs the Bayesian Gaussian CANDECOMP/PARAFAC (BGCP) to impute missing speed data in different missing rates and missing scenarios. Moreover, the dataset is built while considering both the temporal and the road functions. Applying the generated results of data imputation in accident detection is also of the main targets of this work. Thus, while combining multiple sources of data, such as traffic operation status and weather, eXtreme Gradient Boosting (XGBoost) is deployed to build accident detection models. The generated results show that the BGCP model can produce accurate imputations even under temporally correlated data corruption. Added to that, it is also suggested that, when there are continuous periods of missing speed data (missing rate greater than 10%), pre-processing of data imputation is imperative to maintain the accuracy of accident detection. Thus, the objective of this work is to provide insights into traffic management and academics when performing spatiotemporal data imputation tasks.

Cyproheptadine hydrochloride inhibits African swine fever viral replication in vitro.

African swine fever (ASF) is an infectious disease caused by the African swine fever virus (ASFV), and has a high mortality rate. It has caused serious socioeconomic consequences worldwide. Currently, there are no available commercial vaccines or antiviral drug interventions. D1133L is one of the key genes for ASFV replication and antiviral drug screening. In this study, a virtual screening software program, PyRx, was used to screen libraries of compounds against the potential drug target D1133L. Twelve compounds with a high affinity for ASFV D1133L were screened, and cyproheptadine hydrochloride (periactin) was identified as a candidate drug. The periactin has little cytotoxicity, and which dose-dependently inhibited ASFV replication in vitro. Further research indicated that periactin could significantly down-regulate D1133L at the transcriptional and protein levels with RT-qPCR and western blot methods. This study has provided important candidate drugs for the prevention and treatment of ASF, as well as biological materials and new fields of view for the research and development of vaccines and drugs for ASFV.

Amino acid ionic liquid-based magnetic dispersive solid-phase extraction for benzimidazole residue analysis in fruit juice and human serum based on theoretical screening.

The theoretical screening and design of green solvents to reduce organic solvents and to develop green and efficient sample pretreatment methods have attracted extensive attention. Here, benzimidazoles (BZDs) with potential reproductive toxicity were used as target compounds, and amino acid ionic liquids (AAILs) were designed and selected via a theoretical calculation. With the functionalized AAIL as monomers, and POSS as the crosslinking agent, novel specific magnetic nanoparticles (Fe3O4@SiO2@MAPs@AAIL-POSS) were prepared and used to develop the magnetic dispersive solid-phase extraction (MDSPE) of trace BZDs from fruit juice and human serum. In the evaluation of the method, Fe3O4@SiO2@MAPs@AAIL-POSS showed specific adsorption, recyclable ability, high adsorption efficiency, a good recovery rate, and a low coefficient of variation. In addition, the adsorption behavior of Fe3O4@SiO2@MAPs@AAIL-POSS on BZDs was verified by investigating the kinetic and thermodynamic of the adsorption process. The study design provides ideas for green rapid detection methods of other food pollutants.

Effect of Scanning Speed on Properties of Laser Surface Remelted 304 Stainless Steel.

In order to study the microstructure and properties of stainless steel after laser surface remelting, based on the theory of laser surface remelting, a simulation model of nanosecond-pulsed laser surface remelted stainless steel was established to study the evolution law of the Marangoni force of the molten pool during laser surface remelting. A single-lane laser remelting experiment was performed to study the variation of the scanning speed on the remelting width, roughness, and layer microtopography. The "S" scanning path was used to remelt the stainless steel surface to investigate the bonding force between the remelted layer and the substrate, the hardness, microscopic morphology, and corrosion resistance. The results show that the viscosity of the liquid metal in the molten pool increases with the increase of the scanning speed. Larger liquid viscosity and smaller surface tension temperature gradients promote a weaker flow of liquid metal, which reduces the velocity of the liquid metal flow in the molten pool. With the increase of scanning speed, the remelting width gradually decreases, but the roughness gradually increases. When the element content of Cr increases, the element content of Fe and O decreases. The surface is covered with an oxide film, the main components of which are oxides of Cr and Fe, the remelted layer is greater than that of the substrate, and the corrosion resistance is improved. Laser surface remelting technology can improve the structure and properties of 304 stainless steel.

Characteristics of salivary microbiota in children with obstructive sleep apnea: A prospective study with polysomnography.

Objectives: The present study aimed to investigate the characteristics of salivary microbiota of children with obstructive sleep apnea (OSA) and to assess longitudinal alterations in salivary microbiota before and after adenotonsillectomy. Methods: A set of cross-sectional samples consisted of 36 OSA children (17 boys and 19 girls, 7.47 ± 2.24 years old) and 22 controls (9 boys and 13 girls, 7.55 ± 2.48 years old) were included in the study, among which eight OSA children (five boys and three girls, 8.8 ± 2.0 years old) who underwent treatment of adenotonsillectomy were followed up after 1 year. Saliva samples were collected, and microbial profiles were analyzed by bioinformatics analysis based on 16S rRNA sequencing. Results: In cross-sectional samples, the OSA group had higher α-diversity as estimated by Chao1, Shannon, Simpson, Pielou_e, and observed species as compared with the control group (p < 0.05). ß-Diversity based on the Bray-Curtis dissimilarities (p = 0.004) and Jaccard distances (p = 0.001) revealed a significant separation between the OSA group and control group. Nested cross-validated random forest classifier identified the 10 most important genera (Lactobacillus, Escherichia, Bifidobacterium, Capnocytophaga, Bacteroidetes_[G-7], Parvimonas, Bacteroides, Klebsiella, Lautropia, and Prevotella) that could differentiate OSA children from controls with an area under the curve (AUC) of 0.94. Linear discriminant analysis effect size (LEfSe) analysis revealed a significantly higher abundance of genera such as Prevotella (p = 0.027), Actinomyces (p = 0.015), Bifidobacterium (p < 0.001), Escherichia (p < 0.001), and Lactobacillus (p < 0.001) in the OSA group, among which Prevotella was further corroborated in longitudinal samples. Prevotella sp_HMT_396 was found to be significantly enriched in the OSA group (p = 0.02) with significantly higher levels as OSA severity increased (p = 0.014), and it had a lower abundance in the post-treatment group (p = 0.003) with a decline in each OSA child 1 year after adenotonsillectomy. Conclusions: A significantly higher microbial diversity and a significant difference in microbial composition and abundance were identified in salivary microbiota of OSA children compared with controls. Meanwhile, some characteristic genera (Prevotella, Actinomyces, Lactobacillus, Escherichia, and Bifidobacterium) were found in OSA children, among which the relationship between Prevotella spp. and OSA is worth further studies.

The Effects of Heat Treatment on Microstructure and Mechanical Properties of Selective Laser Melting 6061 Aluminum Alloy.

Selective laser melting technology can be used for forming curved panels of 6061 aluminum alloy thermal shield devices for the International Thermonuclear Experimental Reactor (ITER), in order to make the formed parts with better performance. This study proposes different heat treatment processes, including annealed treatment at 300 °C for 2 h, solution treatment at 535 °C and then aging at 175 °C over 2 h, to control the mechanical behavior of the 6061 aluminum alloy samples prepared by selective laser melting (SLM). The mechanical properties such as ductility, tensile strength, and hardness of SLM 6061 aluminum alloy were investigated, and the microstructure of the samples was analyzed. The eutectic silicon skeleton shape disappeared after annealing treatment at 300 °C for 2 h. The tensile strength decreased by 22.86% (from 315 MPa to 243 MPa of the deposited state samples), and the elongation increased from 2.01% to 6.89%. Moreover, the hardness reduced from 120.07 HV0.2 to 89.6 HV0.2. After solution aging, the unique microstructure of SLM disappeared. Furthermore, the precipitation of massive Si particles on the α-Al matrix increased, and a trace amount of the Mg2Si(ß) phase was generated. Compared with the deposited samples, the tensile strength decreased by 12.06%, while the hardness of specimens was 118.8 HV0.2. However, the elongation showed a remarkable increase of 297% (from 2.01% to 7.97%). Therefore, solution aging can critically improve the plasticity without losing significant tensile stress in the SLM 6061 aluminum alloy. This study proposes the use of SLM 6061 aluminum alloy for the thermal shields on the ITER and provides a reference for choosing a reasonable heat-treatment method for the optimal performance of the SLM 6061 aluminum alloy.

Effects of Laser Machining Aluminum Alloy in Different Media.

To study the effects of aluminum alloys processed by a laser in air and water and at different water velocities, corresponding experiments were conducted and the impacting effects of different water velocities on the surface of the workpiece were simulated, respectively. The results show that when laser processing aluminum alloy materials in air, there is more slag and a recondensation layer on both sides of the groove, the heat-affected zone is larger and the surface processing quality is poor. When laser processing aluminum alloy materials in water, the processing quality is improved. With the increase in water velocity, the impacting and cooling effect is enhanced, the groove depth and groove width show a trend of first increasing and then decreasing, the slag and recondensation layer on both sides of the groove are reduced, the heat-affected zone is reduced and the processing quality of the groove is improved. When the water velocity reaches 30 m/s, a better groove can be obtained. Laser processing aluminum alloy materials in water can obtain better processing quality than laser processing in air.

Component Identification and Analysis of Vesicular Fluid From Swine Infected by Foot-and-Mouth Disease Virus.

Foot-and-mouth disease (FMD) is induced by FMD virus (FMDV) and characterized by fever and vesicular (blister-like) lesions. However, the exact composition of the vesicular fluid in pigs infected with FMDV remains unclear. To identify and analyze the components of the vesicular fluid in FMDV-infected domestic pigs, the fluid was collected and subjected to mass spectrometry. Further analyses were conducted using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genome (KEGG), and protein-protein interaction (PPI). Quantitative ELISA kit for TNF-α, and IFN-α, IFN-ß, IL-6, IL-10, IL-1ß, and IFN-γ were used to verify the mass spectrometry results. Results showed that 937 proteins were identified in the vesicular fluid from swine after FMDV infection, and bioinformatics analysis indicated that these proteins are related to the innate immune and inflammation pathways. The levels of cytokines involved in the disease-related pathways, tumor necrosis factors, and IL-6 in the fluid samples were significantly increased. This study identified and analyzed the composition of vesicular fluid in pigs after FMD infection for the first time and provided interesting information that help understand the infection and pathogenesis mechanism of FMD. These information will eventually contribute to the prevention and control of FMD.

Altered Salivary Microbiota in Patients with Obstructive Sleep Apnea Comorbid Hypertension.

Purpose: Microorganisms contribute to the pathogenesis of obstructive sleep apnea (OSA)-associated hypertension (HTN), while more studies focus on intestinal microbiome. However, the relationship between oral microbiota and OSA-associated HTN has yet to be elucidated. This study aimed to identify differences in salivary microbiota between patients with OSA comorbid HTN compared with OSA patients, and furthermore evaluate the relationship between oral microbiome changes and increased blood pressure in patients with OSA. Patients and Methods: This study collected salivary samples from 103 participants, including 27 healthy controls, 27 patients with OSA, 23 patients with HTN, and 26 patients with OSA comorbid HTN, to explore alterations of the oral microbiome using 16S rRNA gene V3-V4 high-throughput sequencing. And ultra-high-performance liquid chromatography was used for metabolomic analysis. Results: Alpha- and beta-diversity analyses revealed a substantial difference in community structure and diversity in patients with OSA comorbid HTN compared with patients with OSA or HTN. The relative abundance of the genus Actinomyces was significantly decreased in patients with HTN compared with healthy controls, and those with OSA concomitant HTN compared with the patients in OSA, but was not significantly different between patients with OSA and healthy controls. Linear discriminant analysis effect size and variance analysis also indicated that the genera Haemophilus, Neisseria, and Lautropia were enriched in HTN. In addition, Oribacterium was an unique taxa in the OSA comorbid HTN group compared with the control group. Metabolomic analysis of saliva identified compounds associated with cardiovascular disease in patients with OSA comorbid HTN.2-hydroxyadenine, was significantly increased in the group of patients with OSA compared with controls, and L-carnitine was significantly decreased in patients with OSA comorbid HTN compared with OSA patients. Conclusion: This study highlighted noninvasive biomarkers for patients with OSA comorbid HTN. As the first study to find alterations of the salivary microbiome in patients with OSA comorbid HTN, it may provide a theoretical foundation for clinical diagnosis and treatment of this condition.

CD146 Associates with Gp130 to Control a Macrophage Pro-inflammatory Program That Regulates the Metabolic Response to Obesity.

The mechanism of obesity-related metabolic dysfunction involves the development of systemic inflammation, largely mediated by macrophages. Switching of M1-like adipose tissue macrophages (ATMs) to M2-like ATMs, a population of macrophages associated with weight loss and insulin sensitivity, is considered a viable therapeutic strategy for obesity-related metabolic syndrome. However, mechanisms for reestablishing the polarization of ATMs remain elusive. This study demonstrates that CD146+ ATMs accumulate in adipose tissue during diet-induced obesity and are associated with increased body weight, systemic inflammation, and obesity-induced insulin resistance. Inactivating the macrophage CD146 gene or antibody targeting of CD146 alleviates obesity-related chronic inflammation and metabolic dysfunction. Macrophage CD146 interacts with Glycoprotein 130 (Gp130), the common subunit of the receptor signaling complex for the interleukin-6 family of cytokines. CD146/Gp130 interaction promotes pro-inflammatory polarization of ATMs by activating JNK signaling and inhibiting the activation of STAT3, a transcription factor for M2-like polarization. Disruption of their interaction by anti-CD146 antibody or interleukin-6 steers ATMs toward anti-inflammatory polarization, thus attenuating obesity-induced chronic inflammation and metabolic dysfunction in mice. The results suggest that macrophage CD146 is an important determinant of pro-inflammatory polarization and plays a pivotal role in obesity-induced metabolic dysfunction. CD146 could constitute a novel therapeutic target for obesity complications.

Profiling and functional analysis of differentially expressed circular RNAs identified in foot-and-mouth disease virus infected PK-15 cells.

Circular RNAs (circRNAs) are a new type of endogenous noncoding RNA that exhibit a variety of biological functions. However, it is not clear whether they are involved in foot-and-mouth disease virus (FMDV) infection and host response. In this study, we established circRNA expression profiles in FMDV-infected PK-15 cells using RNA-seq (RNA-sequencing) technology analysis. The biological function of the differentially expressed circRNAs was determined by protein interaction network, Gene Ontology (GO), and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment. We found 1100 differentially expressed circRNAs (675 downregulated and 425 upregulated) which were involved in various biological processes such as protein ubiquitination modification, cell cycle regulation, RNA transport, and autophagy. We also found that circRNAs identified after FMDV infection may be involved in the host cell immune response. RNA-Seq results were validated by circRNAs qRT-PCR. In this study, we analyzed for the first time circRNAs expression profile and the biological function of these genes after FMDV infection of host cells. The results provide new insights into the interactions between FMDV and host cells.

Functional Analysis and Proteomics Profiling of Extracellular Vesicles From Swine Plasma Infected by African Swine Fever Virus.

African swine fever (ASF) has brought excellent barriers to swine production in China and the world. Studies have shown that extracellular vesicles mediate the RNA and protein spread of pathogenic microorganisms and RNA and proteins. After infection by pathogenic microorganisms causes significant differences in the proteins contained within extracellular vesicles. Based on the above studies, the extracellular vesicles were extracted from ASF virus (ASFV)-infected swine plasma. And qPCR, western blot, and confocal experiment were carried out. The research shows that extracted extracellular vesicles significantly promote the replication of ASFV in susceptible and non-susceptible cells Proteomics analysis of the extracellular vesicle proteins revealed that ASFV infection could cause significant differences in the protein profile. This study demonstrates that extracellular vesicles play a critical role in ASFV replication and transmission and cause significant differences in the protein profile encapsulated in extracellular vesicles.

Re-engineering the inner surface of ferritin nanocage enables dual drug payloads for synergistic tumor therapy.

Rationale: With the advantages of tumor-targeting, pH-responsive drug releasing, and biocompatibility, ferritin nanocage emerges as a promising drug carrier. However, its wide applications were significantly hindered by the low loading efficiency of hydrophobic drugs. Herein, we redesigned the inner surface of ferritin drug carrier (ins-FDC) by fusing the C- terminus of human H ferritin (HFn) subunit with optimized hydrophobic peptides. Methods: Hydrophobic and hydrophilic drugs were encapsulated into the ins-FDC through the urea-dependent disassembly/reassembly strategy and the natural drug entry channel of the protein nanocage. The morphology and drug loading/releasing abilities of the drug-loaded nanocarrier were then examined. Its tumor targeting character, system toxicity, application in synergistic therapy, and anti-tumor action were further investigated. Results: After optimization, 39 hydrophobic Camptothecin and 150 hydrophilic Epirubicin were encapsulated onto one ins-FDC nanocage. The ins-FDC nanocage exhibited programed drug release pattern and increased the stability and biocompatibility of the loaded drugs. Furthermore, the ins-FDC possesses tumor targeting property due to the intrinsic CD71-binding ability of HFn. The loaded drugs may penetrate the brain blood barrier and accumulate in tumors in vivo more efficiently. As a result, the drugs loaded on ins-FDC showed reduced side effects and significantly enhanced efficacy against glioma, metastatic liver cancer, and chemo-resistant breast tumors. Conclusions: The ins-FDC nanocarrier offers a promising novel means for the delivery of hydrophobic compounds in cancer treatments, especially for the combination therapies that use both hydrophobic and hydrophilic chemotherapeutics.