Interior decorative volatile organic compounds exposure induces sleep disorders through aberrant branched chain amino acid transaminase 2 mediated glutamatergic signaling resulting from a neuroinflammatory cascade.

Air pollution has been recognized as a contributing factor to sleep disorders (SD), which have been correlated with an elevated susceptibility to a variety of human diseases. Nevertheless, research has not definitively established a connection between SD and interior decorative volatile organic compounds (ID-VOCs), a significant indoor air pollutant. In this study, we employed a mouse model exposed to ID-VOCs to explore the impacts of ID-VOCs exposure on sleep patterns and the potential underlying mechanism. Of the 23 key compositions of ID-VOCs identified, aromatic hydrocarbons were found to be the most prevalent. Exposure to ID-VOCs in mice resulted in SD, characterized by prolonged wake fullness and decreased sleep during the light period. ID-VOCs exposure triggered neuroinflammatory responses in the suprachiasmatic nucleus (SCN), with microglia activation leading to the overproduction of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), and complement component 1q (C1q), ultimately inducing A1 astrocytes. Consequently, the upregulation of branched chain amino acid transaminase 2 (BCAT2) in A1 astrocytes resulted in elevated extracellular glutamate and disruption of the wake-sleep transition mechanism, which might be the toxicological mechanism of SD caused by ID-VOCs.

Surface Finish Analysis of Gradient Voltage Electrochemical Polishing of 316L Stainless Steel Parts Forming by Laser Powder Bed Fusion.

Laser powder bed fusion (LPBF) of complex-structure 316L stainless steel (316L ss) parts has a wide application prospects in aerospace, biomedical, and defense industry fields. However, the surface roughness (Ra) of the LPBF sample is unsatisfactory due to the process characteristics of layer-by-layer selective melting and cumulative forming, which limits its applications in the engineering field. Herein, a gradient voltage electrochemical polishing strategy is proposed based on the characteristics of electrochemical polishing technology, which can polish complex structures. The mechanisms of polishing process parameters and polishing strategy on the surface finish of LPBF parts are investigated. The gradient voltage polishing strategy is extended to complex structures, and the Ra of the inner surfaces of square and round tubes are successfully reduced to about 1 µm. The gradient electrochemical polishing process for surface finish post-treatment of LPBF parts can broaden the engineering applications of complex-structure metal parts.

Oxidized low-density lipoprotein changes the inflammatory status and metabolomics profiles in human and mouse macrophages and microglia.

The conjunctiva of primary open angle glaucoma patients showed high level of oxidized low-density lipoprotein (ox-LDL), which is associated with the inflammatory response. Microglia and macrophages are the immune cells involved in retinal ganglion cell survival regulation; yet, their roles of the ox-LDL-induced inflammation in glaucoma remain elusive. Here we aimed to investigate the lipid uptake, inflammatory cytokine expression, and metabolomics profiles of human and murine-derived microglial and macrophage cell lines treated with ox-LDL. Under the same ox-LDL concentration, macrophages exhibited higher lipid uptake and expression of pro-inflammatory cytokines as compared to microglia. The ox-LDL increased the levels of fatty acid metabolites in macrophages and sphingomyelin metabolites in microglia. In summary, this study revealed the heterogeneity in the inflammatory capacity and metabolic profiles of macrophages and microglia under the stimulation of ox-LDL.

Profile of Lipoprotein Subclasses in Chinese Primary Open-Angle Glaucoma Patients.

To investigate the plasma lipoprotein subclasses in patients with primary open-angle glaucoma (POAG), a total of 20 Chinese POAG patients on intraocular pressure (IOP)-lowering treatment and 20 age-matched control subjects were recruited. Based on the levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), the study subjects were divided into elevated- and normal-level subgroups. The plasma lipoprotein, lipoprotein subclasses, and oxidized LDL (oxLDL) levels were quantitatively measured. The discrimination potential of the lipoproteins was evaluated using the area under the receiver operating characteristic curve (AUC), and their correlation with clinical parameters was also evaluated. Compared to the control subjects with elevated TC and/or LDL-C levels, the levels of TC, LDL-C, non-high-density lipoprotein cholesterol (non-HDL), LDL subclass LDL3 and small dense LDL (sdLDL), and oxLDL were significantly higher in POAG patients with elevated TC and/or LDL-C levels. No differences in any lipoproteins or the subclasses were found between the POAG patients and control subjects with normal TC and LDL-C levels. Moderate-to-good performance of TC, LDL-C, non-HDL, LDL3, sdLDL, and oxLDL was found in discriminating between the POAG patients and control subjects with elevated TC and/or LDL-C levels (AUC: 0.710-0.950). Significant negative correlations between LDL3 and sdLDL with retinal nerve fiber layer (RNFL) thickness in the superior quadrant and between LDL3 and average RNFL thickness were observed in POAG patients with elevated TC and/or LDL-C levels. This study revealed a significant elevation of plasma lipoproteins, especially the LDL subclasses, in POAG patients with elevated TC and/or LDL-C levels, providing insights on monitoring specific lipoproteins in POAG patients with elevated TC and/or LDL-C.

Untargeted and Oxylipin-Targeted Metabolomics Study on the Plasma Samples of Primary Open-Angle Glaucoma Patients.

Purpose: to determine the metabolomics profiles in the plasma samples of primary open-angle glaucoma (POAG) patients. Methods: The plasma samples from 20 POAG patients under intraocular pressure (IOP)-lowering medication treatment and 20 control subjects were subjected to the untargeted metabolomics analysis, among which 10 POAG patients and 10 control subjects were further subjected to the oxylipin-targeted metabolomics analysis by liquid chromatography-mass spectrometry analysis. The prediction accuracy of the differentially abundant metabolites was assessed by the receiver operating characteristic curves. Pathway analysis and correlation analysis on the differentially abundant metabolites and clinical and biochemical parameters were also conducted. Results: Untargeted metabolomics profiling identified 33 differentially abundant metabolites in the POAG patients, in which the metabolism of linoleic acid, α-linolenic acid, phenylalanine, and tricarboxylic acid cycle were enriched. The correlation analysis indicated that the differentially abundant metabolites were associated with central corneal thickness, peripapillary retinal nerve fiber layer thickness, visual field defects, and lymphocytes. The oxylipin-targeted metabolomics analysis identified 15-keto-Prostaglandin F2 alpha, 13,14-Dihydro-15-keto-prostaglandin D2, 11-Dehydro-thromboxane B2, 8,9-Epoxyeicosatrienoic acid, and arachidonic acid to be significantly decreased in the POAG patients and enriched in the arachidonic acid (AA) pathway. Conclusions: This study revealed that the metabolites in the arachidonic acid metabolism pathway are differentially abundant, suggesting high IOP may not be the only detrimental factor for optic nerve cell damage in this group of POAG patients. Lipid metabolism instability-mediated alterations in oxylipins and AA pathways may be important in POAG, suggesting that oxidative stress and immune-related inflammation could be valuable directions for future therapeutic strategies.

The interactions of subcellular organelles in pulmonary fibrosis induced by carbon black nanoparticles: a comprehensive review.

Owing to the widespread use and improper emissions of carbon black nanoparticles (CBNPs), the adverse effects of CBNPs on human health have attracted much attention. In toxicological research, carbon black is frequently utilized as a negative control because of its low toxicity and poor solubility. However, recent studies have indicated that inhalation exposure to CBNPs could be a risk factor for severe and prolonged pulmonary inflammation and fibrosis. At present, the pathogenesis of pulmonary fibrosis induced by CBNPs is still not fully elucidated, but it is known that with small particle size and large surface area, CBNPs are more easily ingested by cells, leading to organelle damage and abnormal interactions between organelles. Damaged organelle and abnormal organelles interactions lead to cell structure and function disorders, which is one of the important factors in the development and occurrence of various diseases, including pulmonary fibrosis. This review offers a comprehensive analysis of organelle structure, function, and interaction mechanisms, while also summarizing the research advancements in organelles and organelle interactions in CBNPs-induced pulmonary fibrosis.

Two-stage association study of mitochondrial DNA variants in allergic rhinitis.

BACKGROUND: Correlations between mitochondrial DNA (mtDNA) and allergic rhinitis (AR) have not been reported before. This study aimed to better understand the mitochondrial genome profile with AR and to investigate the associations between AR in China and the mitochondrial genome at a single variant and gene level. METHODS: Mitochondrial sequencing was conducted on a total of 134 unrelated individual subjects (68 patients with AR, 66 healthy controls) at discovery stage. Heteroplasmy was analyzed using the Mann-Whitney U test. Sequence kernel association tests (SKAT) were conducted to study the association between mitochondrial genes and AR. Single-variant analysis was performed using logistic regression analysis and further validated in 120 subjects (69 patients with AR, 51 healthy controls). Candidate genes were further explored based on differences in mRNA and protein abundance in nasal mucosal tissue. RESULTS: In the discovery stage, 886 variants, including 836 SNV and 50 indels, were identified with mitochondrial sequencing. No statistically significant differences were identified for the mitochondrial heteroplasmy or SKAT analysis between these two groups after applying a Boferroni correction. One nonsynonymous variants, rs3135028 (MT8584.G/A) in ATP6, was related to a reduced risk of AR in both the discovery and validation cohorts. Furthermore, mRNA levels of MT-ATP6 in nasal mucosal tissue were significantly lower in AR individuals than in controls (P < 0.05). CONCLUSIONS: In a two-stage analysis of associations between AR and mtDNA variations, mitochondrial gene maps of Chinese patients with AR indicated that the ATP6 gene was probably associated with AR at the single-variant level.

Novel-Ink-Based Direct Ink Writing of Ti6Al4V Scaffolds with Sub-300 µm Structural Pores for Superior Cell Proliferation and Differentiation.

Ti6Al4V scaffolds with pore sizes between 300 and 600 µm are deemed suitable for bone tissue engineering. However, a significant proportion of human bone pores are smaller than 300 µm, playing a crucial role in cell proliferation, differentiation, and bone regeneration. Ti6Al4V scaffolds with these small-sized pores are not successfully fabricated, and their cytocompatibility remains unknown. The study presents a novel ink formula specifically tailored for fabricating Ti6Al4V scaffolds featuring precise and unobstructed sub-300 µm structural pores, achieved by investigating the rheological properties and printability of five inks containing 60-77.5 vol% Ti6Al4V powders and bisolvent binders. Ti6Al4V scaffolds with 50-600 µm pores are fabricated via direct ink writing and subjected to in vitro assays with MC3T3-E1 and bone marrow mesenchymal stem cells. The 100 µm pore-sized scaffolds exhibit the highest cell adhesion and proliferation capacity based on live/dead assay, FITC-phalloidin/4',6-diamidino-2-phenylindole staining, and cell count kit 8 assay. The alizarin red staining, real-time quantitative PCR assay, and immunocytochemical staining demonstrate the superior osteogenic differentiation potential of 100 and 200 µm pore-sized scaffolds. The importance of sub-300 µm structrual pores is highlighted, redefining the optimal pore size for Ti6Al4V scaffolds and advancing bone tissue engineering and clinical medicine development.

Periplogenin inhibits pathologic synovial proliferation and infiltration in rheumatoid arthritis by regulating the JAK2/3-STAT3 pathway.

Rheumatoid arthritis (RA) is an autoimmune disease that affects joints, causing inflammation, synovitis, and erosion of cartilage and bone. Periplogenin is an active ingredient in the anti-rheumatic and anti-inflammatory herb, cortex periplocae. We conducted a study using a CIA model and an in vitro model of fibroblast-like synoviocytes (FLS) induced by Tumor Necrosis Factor-alpha (TNF-α) stimulation. We evaluated cell activity, proliferation, and migration using the CCK8 test, EDU kit, and transwell assays, as well as network pharmacokinetic analysis of periplogenin targets and RA-related effects. Furthermore, we measured inflammatory factors and matrix metalloproteinases (MMPs) expression using ELISA and qRT-PCR assays. We also evaluated joint destruction using HE and Safranin O-Fast Green Staining and examined the changes in the JAK2/3-STAT3 pathway using western blot. The results indicated that periplogenin can effectively inhibit the secretion of inflammatory factors, suppress the JAK2/3-STAT3 pathway, and impede the proliferation and migration of RA FLS. Thus, periplogenin alleviated the Synovial inflammatory infiltration of RA.

Study on Osseointegration Capability of ß-Type Ti-Nb-Zr-Ta-Si Alloy for Orthopedic Implants.

Osseointegration is the basic condition for orthopedic implants to maintain long-term stability. In order to achieve osseointegration, a low elastic modulus is the most important performance indicator. It is difficult for traditional titanium alloys to meet this requirement. A novel ß-titanium alloy (Ti-35Nb-7Zr-5Ta)98Si2 was designed, which had excellent strength (a yield strength of 1296 MPa and a breaking strength 3263 MPa), an extremely low elastic modulus (37 GPa), and did not contain toxic elements. In previous in vitro studies, we confirmed the good biocompatibility of this alloy and similar bioactivity to Ti-6Al-4V, but no in vivo study was performed. In this study, Ti-6Al-4V and (Ti-35Nb-7Zr-5Ta)98Si2 were implanted into rabbit femurs. Imaging evaluation and histological morphology were performed, and the bonding strength and bone contact ratio of the two alloys were measured and compared. The results showed that both alloys remained in their original positions 3 months after implantation, and neither imaging nor histological observations found inflammatory reactions in the surrounding bone. The bone-implant contact ratio and bonding strength of (Ti-35Nb-7Zr-5Ta)98Si2 were significantly higher than those of Ti-6Al-4V. The results confirmed that (Ti-35Nb-7Zr-5Ta)98Si2 has a better osseointegration ability than Ti-6Al-4V and is a promising material for orthopedic implants.

Hub gene ELK3-mediated reprogramming lipid metabolism regulates phenotypic switching of pulmonary artery smooth muscle cells to develop pulmonary arterial hypertension induced by PM2.5.

Fine particulate matter (PM2.5) as an environmental pollutant is related with respiratory and cardiovascular diseases. Pulmonary arterial hypertension (PAH) was characterized by incremental pulmonary artery pressure and pulmonary arterial remodeling, leading to right ventricular hypertrophy, and finally cardiac failure and death. The adverse effects on pulmonary artery and the molecular biological mechanism underlying PM2.5-caused PAH has not been elaborated clearly. In the current study, the ambient PM2.5 exposure mice model along with HPASMCs models were established. Based on bioinformatic methods and machine learning algorithms, the hub genes in PAH were screened and then adverse effects on pulmonary artery and potential mechanism was studied. Our results showed that chronic PM2.5 exposure contributed to increased pulmonary artery pressure, pulmonary arterial remodeling and right ventricular hypertrophy in mice. In vitro, PM2.5 induced phenotypic switching in HPASMCs, which served as the early stage of PAH. In mechanism, we investigated that PM2.5-mediated mitochondrial dysfunction could induce phenotypic switching in HPASMCs, which was possibly through reprogramming lipid metabolism. Next, we used machine learning algorithm to identify ELK3 as potential hub gene for mitochondrial fission. Besides, the effect of DNA methylation on ELK3 was further detected in HPASMCs after PM2.5 exposure. The results provided novel directions for protection of pulmonary vasculature injury, against adverse environmental stimuli. This work also provided a new idea for the prevention of PAH, as well as provided experimental evidence for the targeted therapy of PAH.

Minor stroke patients with mild-moderate diastolic blood pressure derive greater benefit from dual antiplatelet therapy.

Not only systolic blood pressure (SBP) but also diastolic blood pressure (DBP) increases the risk of recurrence in the short- or long-term outcomes of stroke. The interaction between DBP and antiplatelet treatment for China stroke patients is unclear. This multicenter, observational cohort study included 2976 minor ischemic stroke patients. Patients accepted single antiplatelet therapy (SAPT) or dual antiplatelet therapy (DAPT) after arrival, and baseline DBP levels were trichotomized into <90 mmHg, 90-110 mmHg and ≥110 mmHg. We explore the interaction effect between antiplatelet therapy and DBP on 90-days composite vascular events. A total of 257 (8.6%) patients reached a composite vascular event during follow-up. The interaction term between DBP levels and treatment group (SAPT vs. DAPT) was significant (P for interaction = 0.013). DAPT's adjusted HR for composite events in patients with DBP between 90 and 110 mmHg was 0.56 (95% confidence interval, 0.36 0.88; P = 0.011) and DBP ≥ 110 mmHg was 4.35 (95% confidence interval, 1.11-19.94; P = 0.046). The association between treatment and DBP was still consistent after propensity score matching of the baseline characteristics. The interaction term of DBP × treatment was not significant for the safety outcomes of severe bleeding (P for interaction = 0.301) or hemorrhage stroke (P for interaction = 0.831). In this cohort study based on the real world, patients with a DBP between 90 and 110 mmHg received a greater benefit from 90 days of DAPT than those with lower and higher baseline DBP. REGISTRATION: ( https://www.chictr.org.cn ; Unique identifier: ChiCTR1900025214).

Artificial Intelligence-based database for prediction of protein structure and their alterations in ocular diseases.

The aim of the study is to establish an online database for predicting protein structures altered in ocular diseases by Alphafold2 and RoseTTAFold algorithms. Totally, 726 genes of multiple ocular diseases were collected for protein structure prediction. Both Alphafold2 and RoseTTAFold algorithms were built locally using the open-source codebases. A dataset with 48 protein structures from Protein Data Bank (PDB) was adopted for algorithm set-up validation. A website was built to match ocular genes with the corresponding predicted tertiary protein structures for each amino acid sequence. The predicted local distance difference test-Cα (pLDDT) and template modeling (TM) scores of the validation protein structure and the selected ocular genes were evaluated. Molecular dynamics and molecular docking simulations were performed to demonstrate the applications of the predicted structures. For the validation dataset, 70.8% of the predicted protein structures showed pLDDT greater than 90. Compared to the PDB structures, 100% of the AlphaFold2-predicted structures and 97.9% of the RoseTTAFold-predicted structure showed TM score greater than 0.5. Totally, 1329 amino acid sequences of 430 ocular disease-related genes have been predicted, of which 75.9% showed pLDDT greater than 70 for the wildtype sequences and 76.1% for the variant sequences. Small molecule docking and molecular dynamics simulations revealed that the predicted protein structures with higher confidence scores showed similar molecular characteristics with the structures from PDB. We have developed an ocular protein structure database (EyeProdb) for ocular disease, which is released for the public and will facilitate the biological investigations and structure-based drug development for ocular diseases. Database URL:  http://eyeprodb.jsiec.org.

Association between household and outdoor air pollution and risk for metabolic syndrome among women in Beijing, China.

This study explored whether household and outdoor air pollution is associated with a greater risk for metabolic syndrome (MetS) among women. In all 11,860 women who cooked with clean energy were included in the analysis. Cooking frequency, range hood use during cooking, passive smoking exposure, and solid fuel use for heating were used to represent household air pollution. The 2-year average concentration of PM2.5, and face mask usage were used to reflect outdoor air pollution exposure. An index of air pollution exposure was also constructed. Multivariable logistic regression models were used to estimate the association between air pollution and risk for MetS, and a positive correlation was found. Our results indicated that household cooking used clean energy and exposure to a high level of outdoor PM2.5 without face mask usage may contribute to an increased risk for MetS among women.

Optical Fiber Temperature and Humidity Dual Parameter Sensing Based on Fiber Bragg Gratings and Porous Film.

A porous anodic alumina film is proposed to construct an optical fiber temperature and humidity sensor. In the sensor structure, a fiber Bragg grating is used to detect the environment temperature, and the porous film is used to detect the environment humidity. The proposed porous anodic alumina film was fabricated by anodic oxidation reaction, and it is suitable for the use of humidity detection due to its porous structure. Experimental results show the temperature sensitivity of the proposed sensor was 10.4 pm/°C and the humidity sensitivity of the proposed sensor was 185 pm/%RH.

Research on named entity recognition of Traditional Chinese Medicine chest discomfort cases incorporating domain vocabulary features.

OBJECTIVE: To promote research on knowledge extraction and knowledge graph construction of chest discomfort medical cases in Traditional Chinese Medicine (TCM), this paper focuses on their named entity recognition (NER). The recognition task includes six entity types: "syndrome", "symptom", "etiology and pathogenesis", "treatment method", "medication", and "prescription". METHODS: We annotated data in a BIO (B-begin, I-inside, O-outside) manner. For the characteristics of medical case texts, we proposed a custom dictionary method that can be dynamically updated for word segmentation. To compare the effect of the method on the experimental results, we applied the method in the BiLSTM-CRF model and IDCNN-CRF model, respectively. RESULTS: The models using custom dictionaries (BiLSTM-CRF-Loaded and IDCNN-CRF-Loaded) outperformed the models without custom dictionaries (BiLSTM-CRF and IDCNN-CRF) in accuracy, precision, recall, and F1 score. The BiLSTM-CRF-Loaded model yielded F1 scores of 92.59% and 93.23% on the test set and validation set, respectively, surpassing the BERT-BiLSTM-CRF model by 3.59% and 4.87%. Furthermore, when analyzing the results for the six entity categories separately, we found that the use of custom dictionaries has a marked impact, with the categories of "etiology and pathogenesis" and "syndrome" demonstrating the most noticeable improvements. By comparing the F1 scores, we observed that the entity category "medication" yielded the highest performance, reaching F1 scores of 96.04% and 96.48% on the test set and validation set, respectively. CONCLUSION: We propose a word segmentation method based on a dynamically updated custom dictionary. The method is combined with the BILSTM-CRF and the IDCNN-CRF models, which enhances the model to recognize domain-specific terms and new entities. It can be widely applied in dealing with complex text structures and texts containing domain-specific terms.

Molecular Drug Simulation and Experimental Validation of the CD36 Receptor Competitively Binding to Long-Chain Fatty Acids by 7-Ketocholesteryl-9-carboxynonanoate.

Long-chain fatty acids (LCFAs) are one of the main energy-supplying substances in the body. LCFAs with different lengths and saturations may have contrasting biological effects that exacerbate or alleviate progress against a variety of systemic disorders of lipid metabolism in organisms. Nonalcoholic fatty liver disease is characterized by chronic inflammation and steatosis, mainly caused by the ectopic accumulation of lipids in the liver, especially LCFAs. CD36 is a scavenger receptor that recognizes and mediates the transmembrane absorption of LCFAs and is expressed in a variety of cells throughout the body. In previous studies, our group found that 7-ketocholesteryl-9-carboxynonanoate (oxLig-1) has the biological effect of targeting CD36 to inhibit oxidized low-density lipoprotein lipotoxicity-induced lipid metabolism disorder; it has an ω-carboxyl physiologically active center and is structurally similar to LCFAs. However, the biological mechanism of oxLig-1 binding to CD36 and competing for binding to different types of LCFAs is still not clear. In this study, molecular docking and molecular dynamics simulation were utilized to simulate and analyze the binding activity between oxLig-1 and different types of LCFAs to CD36 and confirmed by the enzyme-linked immunosorbent assay (ELISA) method. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) platform was applied to predict the drug-forming properties of oxLig-1, and HepG2 cells model of oleic acid and nonalcoholic fatty liver disease (NAFLD) model mice were validated to verify the biological protection of oxLig-1 on lipid lowering. The results showed that there was a co-binding site of LCFAs and oxLig-1 on CD36, and the binding driving forces were mainly hydrogen bonding and hydrophobic interactions. The binding abilities of polyunsaturated LCFAs, oxLig-1, monounsaturated LCFAs, and saturated LCFAs to CD36 showed a decreasing trend in this order. There was a similar decreasing trend in the stability of the molecular dynamics simulation. ELISA results similarly confirmed that the binding activity of oxLig-1 to CD36 was significantly higher than that of typical monounsaturated and saturated LCFAs. ADMET prediction results indicated that oxLig-1 had a good drug-forming property. HepG2 cells model of oleic acid and NAFLD model mice study results demonstrated the favorable lipid-lowering biological effects of oxLig-1. Therefore, oxLig-1 may have a protective effect by targeting CD36 to inhibit the excessive influx and deposition of lipotoxicity monounsaturated LCFAs and saturated LCFAs in hepatocytes.

Chondrocyte-laden gelatin/sodium alginate hydrogel integrating 3D printed PU scaffold for auricular cartilage reconstruction.

Clinically, modified autologous rib cartilage grafts and commercial implants are commonly used for intraoperative repair of auricular cartilage defects caused by injuries. However, scaffold implantation is often accompanied by various complications including absorption and collapse, resulting in undesirable clinical outcomes. Three-dimensional printed auricular cartilage scaffolds have the advantage of individual design and biofunctionality, which attracted tremendous attention in this field. In this study, to better simulate the mechanical properties of auricular cartilage, we tested PU treated by ultrasonication and high temperature for 30 min (PU-30) or 60 min (PU-60). The results indicated that the compression modulus of PU-30 was 2.21-2.48 MPa, which similar to that of natural auricular cartilage (2.22-7.23 MPa) and was chosen for subsequent experiments. And the pores of treated PU were filled with a gelatin/sodium alginate hydrogel loaded with chondrocytes. In vivo analysis using a rabbit model confirmed that implanted PU-30 scaffold filled with chondrocytes contained hydrogel successfully integrated with normal auricular cartilage, and that new cartilage was generated at the scaffold-tissue interface by histological examination. These findings illustrate that this engineered scaffold represents a potential strategy for repair of ear cartilage damage in clinical.

Protective effects of nattokinase against microvasculopathy and neuroinflammation in diabetic retinopathy.

AIMS: Diabetic retinopathy (DR) is a significant global public health concern. Alternative, safe, and cost-effective pharmacologic approaches are warranted. We aimed to investigate the therapeutic potential of nattokinase (NK) for early DR and the underlying molecular mechanism. METHODS: A mouse model of diabetes induced by streptozotocin was utilized and NK was administered via intravitreal injection. Microvascular abnormities were evaluated by examining the leakage from blood-retinal barrier dysfunction and loss of pericytes. Retinal neuroinflammation was examined through the assessment of glial activation and leukostasis. The level of high mobility group box 1 (HMGB1) and its downstream signaling molecules was evaluated following NK treatment. RESULTS: NK administration significantly improved the blood-retinal barrier function and rescued pericyte loss in the diabetic retinas. Additionally, NK treatment inhibited diabetes-induced gliosis and inflammatory response and protected retinal neurons from diabetes-induced injury. NK also improved high glucose-induced dysfunction in cultured human retinal micrangium endothelial cells. Mechanistically, NK regulated diabetes-induced inflammation partially by modulating HMGB1 signaling in the activated microglia. CONCLUSIONS: This study demonstrated the protective effects of NK against microvascular damages and neuroinflammation in the streptozotocin-induced DR model, suggesting that NK could be a potential pharmaceutical agent for the treatment of DR.

Comprehensive Analysis of lncRNA-mRNA Expression Profiles in Depression-like Responses of Mice Related to Polystyrene Nanoparticle Exposure.

Plastics in the environment can break down into nanoplastics (NPs), which pose a potential threat to public health. Studies have shown that the nervous system constitutes a significant target for nanoplastics. However, the potential mechanism behind nanoplastics' neurotoxicity remains unknown. This study aimed to investigate the role of lncRNA in the depressive-like responses induced by exposure to 25 nm polystyrene nanoplastics (PS NPs). Forty mice were divided into four groups administered doses of 0, 10, 25, and 50 mg/kg via gavage for 6 months. After conducting behavioral tests, RNA sequencing was used to detect changes in mRNAs, miRNAs, and lncRNAs in the prefrontal cortex of the mice in the 0 and 50 mg/kg PS NPs groups. The results revealed that mice exposed to chronic PS NPs developed depressive-like responses in a dose-dependent manner. It was demonstrated that 987 mRNAs, 29 miRNAs, and 116 lncRNAs were significantly different between the two groups. Then, a competing endogenous RNA (ceRNA) network containing 6 lncRNAs, 18 miRNAs, and 750 mRNAs was constructed. Enrichment results suggested that PS NPs may contribute to the onset of depression-like responses through the activation of axon guidance, neurotrophin-signaling pathways, and dopaminergic synapses. This study provided evidence of the molecular relationship between PS NPs and depression-like responses.