Interlayer Charge Transfer Induced Electrical Behavior Transition in 1D AgI@sSWCNT van der Waals Heterostructures.

The emergence of one-dimensional van der Waals heterostructures (1D vdWHs) opens up potential fields with unique properties, but precise synthesis remains a challenge. The utilization of mixed conductive types of carbon nanotubes as templates has imposed restrictions on the investigation of the electrical behavior and interlayer interaction of 1D vdWHs. In this study, we efficiently encapsulated silver iodide in high-purity semiconducting single-walled carbon nanotubes (sSWCNTs), forming 1D AgI@sSWCNT vdWHs. We characterized the semiconductor-metal transition and increased the carrier concentration of individual AgI@sSWCNTs via sensitive dielectric force microscopy and confirmed the results through electrical device tests. The electrical behavior transition was attributed to an interlayer charge transfer, as demonstrated by Kelvin probe force microscopy. Furthermore, we showed that this method of synthesizing 1D heterostructures can be extended to other metal halides. This work opens the door for the further exploration of the electrical properties of 1D vdWHs.

NEDD4L mediates ITGB4 ubiquitination and degradation to suppress esophageal carcinoma progression.

The ubiquitination-mediated protein degradation exerts a vital role in the progression of multiple tumors. NEDD4L, which belongs to the E3 ubiquitin ligase NEDD4 family, is related to tumor genesis, metastasis and drug resistance. However, the anti-tumor role of NEDD4L in esophageal carcinoma, and the potential specific recognition substrate remain unclear. Based on public esophageal carcinoma database and clinical sample data, it was discovered in this study that the expression of NEDD4L in esophageal carcinoma was apparently lower than that in atypical hyperplastic esophageal tissue and esophageal squamous epithelium. Besides, patients with high expression of NEDD4L in esophageal carcinoma tissue had longer progression-free survival than those with low expression. Experiments in vivo and in vitro also verified that NEDD4L suppressed the growth and metastasis of esophageal carcinoma. Based on co-immunoprecipitation and proteome analysis, the NEDD4L ubiquitination-degraded protein ITGB4 was obtained. In terms of the mechanism, the HECT domain of NEDD4L specifically bound to the Galx-ß domain of ITGB4, which modified the K915 site of ITGB4 in an ubiquitination manner, and promoted the ubiquitination degradation of ITGB4, thus suppressing the malignant phenotype of esophageal carcinoma.

Multi-omics and multi-stages integration identified a novel variant associated with silicosis risk.

Assessing the association between candidate single-nucleotide polymorphisms (SNPs) identified by multi-omics approaches and susceptibility to silicosis. RNA-seq analysis was performed to screen the differentially expressed mRNAs in the fibrotic lung tissues of mice exposed to silica particles. Following this, we integrated the SNPs located in the above human homologenes with the silicosis-related genome-wide association study (GWAS) data to select the candidate SNPs. Then, expression quantitative trait locus (eQTL)-SNPs were identified by the GTEx database. Next, we validated the associations between the functional eQTL-SNPs and silicosis susceptibility by additional case-control study. And the contribution of the identified SNP and its host gene in the fibrosis process was further validated by functional experiments. A total of 12 eQTL-SNPs were identified in the screening stage. The results of the validation stage suggested that the variant T allele of rs419540 located in IL12RB1 significantly increased the risk of developing silicosis [additive model: odds ratio (OR) = 1.78, 95% confidence interval (CI) 1.11-2.85, P = 0.017]. Furthermore, the combination of GWAS and the results of validation stage also indicated that the variant T allele of rs419540 in IL12RB1 was associated with increased silicosis risk (additive model: OR = 2.07, 95% CI 1.38-3.12, P < 0.001). Additionally, after knockdown or overexpression of IL12RB1, the levels of pro-inflammatory factors, such as IL-12, IFN-γ, and other pro-inflammatory factors, were correspondingly decreased or increased. The novel eQTL-SNP, rs419540, might increase the risk of silicosis by modulating the expression levels of IL12RB1.

Integration of apaQTL and eQTL analysis reveals novel SNPs associated with occupational pulmonary fibrosis risk.

To explore the association between apaQTL/eQTL-SNPs and the susceptibility to silicosis. A silicosis-related GWAS was initially conducted to screen for single nucleotide polymorphisms (SNPs) associated with the risk of silicosis. Candidate SNPs with apaQTL and eQTL functions were then obtained from the 3'aQTL-atlas and GTEx databases. Subsequently, additional case-control studies were performed to validate the relationship between the candidate apaQTL/eQTL-SNPs and the risk of silicosis. Finally, experiments were conducted to illustrate APA events occurring at different alleles of the identified apaQTL/eQTL-SNPs. The combined results of the GWAS and iMLDR validations indicate that the variant T allele of the rs2974341 located on SMIM19 (additive model: OR = 0.66, the 95% CI = 0.53-0.84, P = 0.001) and the variant T allele of the rs2390488 located on TMTC4 (additive model: OR = 0.72, 95% CI = 0.57-0.90, P = 0.005) were significantly associated with decreased risk of developing silicosis susceptibility. Furthermore, 3'RACE experiments verified the presence of two poly (A) sites (proximal and distal) in SMIM19, rs2974341 may remotely regulate the binding between miRNA-3646 and SMIM19 with its high LD locus rs2974353 to affect the expression level of SMIM19. The rs2974341 variant T allele may contribute to the generation of the shorter 3'UTR transcript of SMIM19 and affect the binding of miRNA-3646 to the target gene SMIM19. The apaQTL/eQTL-SNPs may provide new perspectives for evaluating the regulatory function of SNPs in the development of silicosis.

Pseudomonas weihenstephanensis through the iron metabolism pathway promotes in situ spoilage capacity of prepared beef steaks during cold storage.

In this study, we evaluated the histomorphology, reactive oxygen species (ROS), protein degradation, and iron metabolism characteristics and differential expression analysis of genes for siderophores synthesis and protease secretion in prepared beef steaks inoculated alone or co-inoculated with P. weihenstephanensis, B. thermotrichothrix and M. caseolyticus at 4 °C for 12 days. The results showed that the P. weihenstephanensis was the key bacteria that degraded protein in the process of prepared beef steaks spoilage, which led to protein oxidation by promoting ferritin degradation to release free iron and inducing ROS accumulation. The highest expression of FpvA and AprE was detected in the P. weihenstephanensis group by comparing qRT-PCR of the different inoculation groups. Both qRT-PCR and Western blot revealed that ferritin heavy polypeptide and ferritin light chain polypeptide gene and protein expressions were significantly higher in the P. weihenstephanensis inoculation group compared to the other inoculation groups. Results suggested that FpvA and AprE might play roles in meat spoilage and were potential positional, physiological and functional candidate genes for improving the quality traits of prepared beef steaks. This work may provide insights on controlling food quality and safety by intervening in spoilage pathways targeting iron carrier biosynthesis or protease secretion genes.

Crosstalk among Alternative Polyadenylation, Genetic Variants and Ubiquitin Modification Contribute to Lung Adenocarcinoma Risk.

Ubiquitin modification and alternative polyadenylation play crucial roles in the onset and progression of cancer. Hence, this study aims to comprehensively and deeply understand gene regulation and associated biological processes in lung adenocarcinoma (LUAD) by integrating both mechanisms. Alternative polyadenylation (APA)-related E3 ubiquitin ligases in LUAD were identified through multiple databases, and the association between selected genetic loci influencing gene expression (apaQTL-SNPs) and LUAD risk were evaluated through the GWAS database of the Female Lung Cancer Consortium in Asia (FLCCA). Subsequently, the interaction between RNF213 and ZBTB20, as well as their functional mechanisms in LUAD, were investigated using bioinformatics analysis, Western blot, co-immunoprecipitation, and colony formation experiments. A total of five apaQTL-SNPs (rs41301932, rs4494603, rs9890400, rs56066320, and rs41301932), located on RNF213, were significantly associated with LUAD risk (p < 0.05), and they inhibit tumor growth through ubiquitin-mediated degradation of ZBTB20.

Revealing the spoilage characteristics of refrigerated prepared beef steak by advanced bioinformatics tools.

BACKGROUND: Although microorganisms are the main cause of spoilage in prepared beef steaks, very few deep spoilage mechanisms have been reported so far. Aiming to unravel the mechanisms during 12 days of storage at 4 °C affecting the quality of prepared beef steak, the present study investigated the changes in microbial dynamic community using a combined high-throughput sequencing combined and bioinformatics. In addition, gas chromatography-mass spectrometry combined with multivariate statistical analysis was utilized to identify marker candidates for prepared steaks. Furthermore, cloud platform analysis was applied to determine prepared beef steak spoilage, including the relationship between microbiological and physicochemical indicators and volatile compounds. RESULTS: The results showed that the dominant groups of Pseudomonas, Brochothrix thermosphacta, Lactobacillus and Lactococcus caused the spoilage of prepared beef steak, which are strongly associated with significant changes in physicochemical properties and volatile organic compounds (furan-2-pentyl-, pentanal, 1-octanol, 1-nonanol and dimethyl sulfide). Metabolic pathways were proposed, among which lipid metabolism and amino acid metabolism were most abundant. CONCLUSION: The present study is helpful with respect to further understanding the relationship between spoilage microorganisms and the quality of prepared beef steak, and provides a reference for investigating the spoilage mechanism of dominant spoilage bacteria and how to extend the shelf life of meat products. © 2024 Society of Chemical Industry.

Recent advances in meat freshness "magnifier": fluorescence sensing.

To address the serious waste of meat resources and food safety problems caused by the decrease in meat freshness due to the action of microorganisms and enzymes, a low-cost, time-saving and high-efficiency freshness monitoring method is urgently needed. Fluorescence sensing could act as a "magnifier" for meat freshness monitoring due to its ability to sense characteristic signal produced by meat spoilage. Here, the magnification mechanism of meat freshness via sensing the water activity, adenosine triphosphate, hydrogen ion, total volatile basic nitrogen, hydrogen sulfide, bioamines was comprehensively analyzed. The existing "magnifier" forms including paper chips, films, labels, arrays, probes, and hydrogels as well as the application in livestock, poultry and aquatic meat freshness monitoring were reviewed. Future research directions involving innovation of principles, visualization and quantification capabilities for various meats freshness were provided. By critically evaluating the potential and limitations, efficient and reliable meat freshness monitoring strategies wish to be developed for the post-epidemic era.

Next-generation meat preservation: integrating nano-natural substances to tackle hurdles and opportunities.

The increasing global meat demand raises concerns regarding the spoilage of meat caused by microbial invasion and oxidative decomposition. Natural substances, as a gift from nature to humanity, possess broad-spectrum bioactivity and have been utilized for meat preservation. However, their limited stability, solubility, and availability hinder their further development. To address this predicament, advanced organic nanocarriers provide an effective shelter for the formation of nano-natural substances (NNS). This review comprehensively presents various natural substances derived from plants, animals, and microorganisms, along with the challenges they face. Subsequently, the potential of organic nanocarriers is explored, highlighting their distinct features and applicability, in addressing these challenges. The review methodically examines the application of NNS in meat preservation, with a focus on their pathways of action and preservation mechanisms. Furthermore, the outlook and future trends for NNS applications in meat preservation are concluded. The theory and practice summary of NNS is expected to serve as a catalyst for advancements that enhance meat security, promote human health, and contribute to sustainable development.

Diversified organic nanocarriers conquer the limitations of natural substancesNNS based on organic nanocarriers are a reliable and health-promoting optionNNS can manifest their effectiveness through diverse pathways and mechanismsThe utilization of NNS in meat preservation represents a transformative strategy.

STARD12/14 are diagnostic and prognostic biomarkers of lung adenocarcinoma associated with epigenetic regulation, immune infiltration and ferroptosis.

Background: Metabolic reprogramming plays an important role in tumor progression and antitumor immunity. START domain-containing proteins (STARDs) are responsible for lipid metabolism. However, the underlying functions of STARDs in lung adenocarcinoma (LUAD) have not been clarified yet. Methods: Oncomine, UALCAN, TCGA and CPTAC were used to explore the expression landscape and clinicopathological characteristics of STARDs in LUAD. Diagnostic and prognostic values were assessed by Kaplan-Meier Plotter, Cox regression analysis, and ROC curve. GeneMANIA, GO, KEGG and GSEA were applied for exploring the potential biological functions. Epigenetic process, including mutation and m6A modification were analyzed by cBioPortal and TCGA. TIMER, TISIDB and TCGA cohort provided an immune signature. The correlation between STARDs expression and ferroptosis was analyzed by TCGA. Finally, the STARDs expression were confirmed by RT-qPCR and western blot. Results: STARD5/10/14 were overexpressed in LUAD compared with normal, while STARD4/7/8/11/12/13 were relatively low. STARD5/12/14 levels were positively related to clinical and lymph node stage. Survival analysis showed high STARD12 expression was associated with favorable overall survival, disease special survival as well as disease free survival, while STARD14 showed the opposite. GSEA analysis found STARD12 and STARD14 were associated with glycolysis, oxidative phosphorylation and tumor related signaling pathways. STARD12 co-expressed genes participated in cell cycle and DNA replication, and STARD14 were enriched in ECM-receptor interaction. Both STARD12 and STARD14 were corelated with epigenetic regulation, especially TP53 mutation and m6A modification. STARD12 expression was positively correlated with TMB level. The level of STARD12 was significantly associated with the abundance of infiltrating immune cells, including B cells, CD8+T cells, macrophages, dendritic cells, and chemokine, receptor, MHC, immunostimulatory related genes. STARD14 was negatively associated with the infiltration of CD8+T cells, while positively with CCL28 and immune checkpoints, including CTLA4 as well as PD-L2. In addition, STARD12/14 could regulate the ferroptosis related genes. Conclusion: STARD12 and STARD14 were expected to be potential biomarkers for LUAD, which were associated with epigenetic regulation, immune infiltration and ferroptosis.

SM22α Deletion Contributes to Neurocognitive Impairment in Mice through Modulating Vascular Smooth Muscle Cell Phenotypes.

Considerable evidence now indicates that cognitive impairment is primarily a vascular disorder. The depletion of smooth muscle 22 alpha (SM22α) contributes to vascular smooth muscle cells (VSMCs) switching from contractile to synthetic and proinflammatory phenotypes in the context of inflammation. However, the role of VSMCs in the pathogenesis of cognitive impairment remains undetermined. Herein, we showed a possible link between VSMC phenotypic switching and neurodegenerative diseases via the integration of multi-omics data. SM22α knockout (Sm22α-/-) mice exhibited obvious cognitive impairment and cerebral pathological changes, which were visibly ameliorated by the administration of AAV-SM22α. Finally, we confirmed that SM22α disruption promotes the expression of SRY-related HMG-box gene 10 (Sox10) in VSMCs, thereby aggravating the systemic vascular inflammatory response and ultimately leading to cognitive impairment in the brain. Therefore, this study supports the idea of VSMCs and SM22α as promising therapeutic targets in cognitive impairment to improve memory and cognitive decline.

Rhamnolipid-induced alleviation of bioclogging in Managed Aquifer Recharge (MAR): Interactions with bacteria and porous media.

The prevention and treatment of bioclogging is of great significance to the application of Managed Aquifer Recharge (MAR). This study investigated the alleviating effect of biosurfactant rhamnolipid (RL) on bioclogging by laboratory-scale percolation experiments. The results show that the addition of RL greatly reduced bioclogging. Compared with the group without RL, the relative hydraulic conductivity (K') of the 100 mg/L RL group increased 5 times at the end of the experiment (23 h), while the bacterial cell amount and extracellular polymeric substances (EPS) content on the sand column surface (0-2 cm) decreased by 60.8% and 85.7%, respectively. In addition, the richness and diversity of the microbial communities within the clogging matter decreased after the addition of RL. A variety of bacterial phyla were found, among which Proteobacteria were predominant in all groups. At the genus level, RL reduced the relative abundance of Acinetobacter, Bacillus, Klebsiella, and Pseudomonas. These microbes are known as strong adhesion, large size, and easy to form biofilms, therefore playing a critical role during MAR bioclogging. Moreover, RL changed the surface properties of bacteria and porous media, which results in the increase of electrostatic repulsion and decrease of hydrophobic interaction between them. Therefore, RL mediated the bacteria-porous media interaction to reduce biomass in porous media, thereby alleviating bioclogging. This study implies that RL's addition is an environmentally friendly and effective method to alleviate the bioclogging in MAR.

Analysis and intervention of heatwave related economic loss: Comprehensive insights from supply, demand, and public expenditure into the relationship between the influencing factors.

Increasing extreme temperatures are producing a serious impact on the economies of cities. However, the importance of social factors is typically neglected by the existing research. In this work, we first establish a supply-demand-public expenditure (SDP) framework for assessing and forecasting heat-related economic loss. Compared with the previous framework, SDP possesses a more comprehensive index system and functions that apply to all types of cities. We selected different economic development and geographical locations (Nanjing, Suzhou, and Yancheng) as case studies to verify the wide applicability of the SDP framework. A qualitative analysis and quantitative prediction of heatwaves and socioeconomic factors on losses were conducted for different cities. The results showed that different loss types displayed obvious regional heterogeneity among the cities. The labor value loss was the most significant type, and health loss was the most vulnerable type. In addition, public expenditure played a neglected critical regulatory role. Apart from these, the current level of public expenditure for heat prevention and control remains insufficient. Based on an assessment of the effects of interventions, policymakers need to make more efforts to increase the proportion of heat-related public spending and ensure stable socio-economic development by utilizing pathways with positive intervention potentials.

Effects of magnetic nanoscale combined radio frequency or microwave thawing on conformation of sea bass myosin heavy chain: a molecular dynamics study.

BACKGROUND: The consumption of frozen foods inevitably involves a thawing process. Protein conformation changes during a short thawing process and the quantification of their effects remains challenging. Molecular dynamics simulations can be used to evaluate the conformational changes of protein occurring in food processing. RESULTS: In the present study, four different thawing methods were used [i.e. magnetic nanometer combined with microwave thawing (MT-Mag), magnetic nanometer combined with radio frequency thawing (RT-Mag), radio frequency thawing (RT) and microwave thawing (MT)] to change the conformation of myosin heavy chain (MHC). The results obtained showed that, compared with the fresh sample, the hydrogen bond number and radius of gyration of the RT-Mag and RT groups were less decreased. Visual molecular dynamics STRIDE analysis showed that the content of the α helix was relatively high in the RT-Mag and MT-Mag groups. CONCLUSION: These simulation results indicate that RT-Mag can be used as an effective method for promoting the thawing process of fish and better stabilizing the protein structure. These conclusions provide a theoretical realization for understanding the protein conformational transition during the thawing process and the realization of quantification and also provide guidance for choosing better thawing conditions without loss of nutritional properties. © 2022 Society of Chemical Industry.

A novel circRNA-SNP may increase susceptibility to silicosis.

In this study, we aimed to reveal the association between circRNA-related single nucleotide polymorphisms (SNPs) with the susceptibility of silicosis. To achieve this goal, a silicosis-related GWAS was constructed to select the candidate SNPs, and circBase database was utilized to select the promising SNPs which may locate on circRNAs. In addition, the eQTL analysis between the SNPs and located genes was performed to select the candidate SNPs. Finally, the association between candidate SNPs with the susceptibility of silicosis was validated. As a result, we firstly selected 10,922 SNPs with P < 1 × 10-3 through the silicosis-related GWAS. Among which, 1,752 SNPs were identified that may locate on 2,660 circRNAs. After the MAF evaluation and the sequences checking, we obtained 94 SNPs and related 105 circRNAs. EQTL analysis indicated that 7 circRNA-SNPs might regulate the expression of located genes. Subsequently, a strong association was found between variant A of rs17115143 and silicosis risk in the validation stage (OR= 1.68, P = 0.032). Combination of the GWAS data and Taqman genotyping data also revealed a strong association between rs17115143 and silicosis risk in both dominant and additive models (dom: OR= 1.96, P = 3.98 × 10-4; add: OR= 1.40, P = 3.06 × 10-4). In conclusion, the variant A allele of circRNA-SNP rs17115143 could be a risk factor in the progression of silicosis. And related 6 circRNAs may function as novel biomarkers for the diagnostic of silicosis. Further researches to explore the biological mechanisms of rs17115143 related 6 circRNAs in the regulation of silicosis are warranted.

JAK2/STAT3 pathway regulates microglia polarization involved in hippocampal inflammatory damage due to acute paraquat exposure.

OBJECTIVE: To explore the effects of acute paraquat (PQ) exposure on the phenotypic polarization of hippocampal microglia and its mechanism. METHODS: An acute PQ exposure rat model was established. Male SD rats were exposed to 0, 5, 25, and 50 mg/kg PQ, and brain hippocampal tissue was collected after 1, 3, and 7 days of exposure, respectively. Hippocampal pathological changes were examined by H&E staining, and immunohistochemistry (IHC) was used to detect changes in the number of Iba-1-positive cells, the average number of endpoints, and the average process length. The protein expression of Iba-1 was detected by western blotting. BV-2 microglia were treated with 0, 0.01, 0.025, 0.05, or 0.1 µmol/L PQ for 24 h. ELISA and western blotting assays were performed to detect the expression of TNF-α and IL-1ß in vivo and in vitro. The M1 microglia marker iNOS, the M2 microglia marker Arg-1, and the p-JAK2 and p-STAT3 protein were detected by western blotting. JAK2/STAT3 pathway activation role in regulating microglia phenotypic polarization was further validated in vivo and in vitro by JAK2-specific inhibitor AG490 administration. RESULTS: After acute PQ exposure, hippocampal neurons showed pathological changes such as loose arrangement and nuclear pyknosis, the number of Iba-1 positive cells and the expression of Iba-1 protein increased, and the average number of endpoints and average process length of microglia decreased. Histological examination revealed that compared with the control group, in the 50 mg/kg PQ group on the 3rd and 7th day, the expression of TNF-α, IL-1ß, and iNOS significantly increased, while that of Arg-1 significantly decreased. p-JAK2 and p-STAT3 expression significantly increased in the 50 mg/kg PQ group on the 1st, 3rd, and 7th day. In vitro, compared with the control group, the expression of TNF-α, IL-1ß, iNOS, p-JAK2, and p-STAT3 significantly increased, while Arg-1 expression was significantly reduced in the 0.025, 0.05, and 0.1 µmol/L PQ groups. After AG490 administration, the expression levels of p-JAK2, p-STAT3, iNOS, TNF-α, and IL-1ß in the AG490 +PQ group were significantly inhibited in vivo and in vitro compared with the PQ-only group. On the contrary, Arg-1 expression was significantly increased. CONCLUSION: Our results suggest that acute PQ exposure may induce M1-type polarization of hippocampal microglia by activating the JAK2/STAT3 pathway, which in turn releases pro-inflammatory factors such as TNF-α and IL-1ß, leading to hippocampal inflammatory damage.

Peripheral blood circular RNA hsa_circ_0058493 as a potential novel biomarker for silicosis and idiopathic pulmonary fibrosis.

Existing studies reported that some circular RNAs (circRNAs) play vital roles in the development of pulmonary fibrosis. However, few studies explored the biomarker potential of circRNAs for pulmonary fibrosis based on population data. Therefore, we aimed to identify peripheral blood circRNAs as potential biomarkers for diagnosing silicosis and idiopathic pulmonary fibrosis (IPF). In brief, an RNA-seq screening based on 4 silicosis cases and 4 controls was initially performed. Differentially expressed circRNAs were combined with the human serum circRNA dataset to identify overlapping serum-detectable circRNAs, followed by validation using the GEO dataset (3 IPF cases and 3 controls) and subsequent qRT-PCR, including 84 additional individuals. Following the above steps, 243 differentially expressed circRNAs were identified during the screening stage, with fold changes ≥ 1.5 and P < 0.05. Of note, the human serum circRNA dataset encompassed 28 of 243 circRNAs. GEO (GSE102660) validation revealed two highly expressed circRNAs (P < 0.05) in the IPF case group. Furthermore, at the enlarged sample validation stage, hsa_circ_0058493 was highly expressed in both silicosis and IPF cases (silicosis: P = 1.16 × 10-6; IPF: P = 7.46 × 10-5). Additionally, hsa_circ_0058493 expression was significantly increased in MRC-5 cells upon TGF-ß1 treatment, while hsa_circ_0058493 knockdown inhibited the expression of fibrotic molecules by affecting the epithelial-mesenchymal transition process. These shreds of evidence indicated that hsa_circ_0058493 might serve as a novel biomarker for diagnosing silicosis and IPF.

IL-27 overexpression alleviates inflammatory response in allergic asthma by inhibiting Th9 differentiation and regulating Th1/Th2 balance.

OBJECTIVE: To investigate the effect of IL-27 on Th9 differentiation and Th1/Th2 balance. METHODS: C57BL/6 (B6) mice were treated with ovalbumin to establish an allergic asthma (AA) model and subjected to IL-27 overexpression (OV) and empty vector (EV). Hematoxylin-eosin (HE) staining was performed to observe lung tissue inflammation. Flow cytometry was carried out to evaluate the percentage of Th9, Th1, and Th2 cells. The expression of IL-27, IL-27R, IL-9, T-bet, IFN-γ, and IgE was evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Western blot was conducted to observe the expression of pSTAT-1 and pSTAT-3. RESULTS: Compared with the Model group, the number of Th1 cells in the Model + OV group increased significantly (p < .05), while those of Th9 and Th2 cells decreased significantly (p < .05). The expression of IL-27, IL-27R, and IFN-γ in blood serum was increased (p < .05), and that of IL-9 and IgE was significantly decreased in the Model + OV group compared to the Model (p < .05). Western blot revealed that Model + OV exhibited lower expression of pSTAT-3 than that in the Model and Model + EV groups (p < .05), while pSTAT-1 expression was significantly increased (p < .05). Inflammatory infiltration in the Model + OV group was significantly reduced, and there was no significant difference between the Model and Model + EV groups. CONCLUSIONS: IL-27 OV inhibits Th9 differentiation and regulates the imbalance of Th1/Th2, thereby alleviating inflammatory response in AA. The findings suggest that IL-27 OV may be a potential strategy for clinical treatment of AA.

Dark-Field Microscopic Study of Cellular Uptake of Carbon Nanodots: Nuclear Penetrability.

Carbon nanodots are fascinating candidates for the field of biomedicine, in applications such as bioimaging and drug delivery. However, the nuclear penetrability and process are rarely studied and lack understanding, which limits their applications for drug carriers, single-molecule detection and live cell imaging. In this study, we attempt to examine the uptake of CNDs in cells with a focus on the potential nuclear penetrability using enhanced dark-field microscopy (EDFM) associated with hyperspectral imaging (HSI) to quantitatively determine the light scattering signals of CNDs in the cells. The effects of both CND incubation time and concentration are investigated, and plausible nuclear penetration involving the nuclear pore complex (NPC) is discussed. The experimental results and an analytical model demonstrate that the CNDs' uptake proceeds by a concentration-dependent three-stage behavior and saturates at a CND incubation concentration larger than 750 µg/mL, with a half-saturated concentration of 479 µg/mL. These findings would potentially help the development of CNDs' utilization in drug carriers, live cell imaging and other biomedical applications.

Transthyretin and retinol-binding protein as discriminators of diabetic retinopathy in type 1 diabetes mellitus.

PURPOSE: Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus (DM), which is still a major reason for blindness. Transthyretin (TTR) and retinol-binding protein (RBP) are thought to be related to the pathogenesis both in T2DM and T1DM. We aimed to investigate the association between serum levels of TTR, RBP, RBP/TTR ratio, and DR. METHODS: This retrospective study involved 188 T1DM inpatients divided into two groups: patients with DR (n = 95) and patients without DR (n = 93). Data of serum levels on lipids and inflammation were collected. Multiple logistic regression analysis was performed to research the association between TTR, RBP, RBP/TTR, and diabetic retinopathy in T1DM. RESULTS: Compared with patients without DR, those with DR have a higher level of TTR (207 versus 195 mg/L, p = 0.034) and RBP4 (36.85 versus 25.68 mg/L, p < 0.001). Significant differences were also observed between two groups with respect to body mass index (BMI), blood pressure (BP), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), homocysteine, apolipoprotein B (APOB), leucocyte, monocyte, neutrophil, and uric acid (p < 0.05 for all). TTR, RBP, and RBP/TTR were positively correlated with BP, BMI, TG, LDL, homocysteine, APOB, and uric acid. A multivariate logistic regression model revealed individuals with RBP4 level in the highest quartile had 58.95 times higher risk of developing diabetic retinopathy than those in the lowest quartile. CONCLUSIONS: In conclusion, TTR, RBP, and RBP/TTR ratio are risk factors of DR in T1DM. They are potential markers and targets for diagnosis and treatment of DR.