Investigating Retinal Explant Models Cultured in Static and Perfused Systems to Test the Performance of Exosomes Secreted from Retinal Organoids.

BACKGROUND: Ex vivo cultures of retinal explants are appropriate models for translational research. However, one of the difficult problems of retinal explants ex vivo culture is that their nutrient supply needs cannot be constantly met. NEW METHOD: This study evaluated the effect of perfused culture on the survival of retinal explants, addressing the challenge of insufficient nutrition in static culture. Furthermore, exosomes secreted from retinal organoids (RO-Exos) were stained with PKH26 to track their uptake in retinal explants to mimic the efficacy of exosomal drugs in vivo. RESULTS: We found that the retinal explants cultured with perfusion exhibited significantly higher viability, increased NeuN+ cells, and reduced apoptosis compared to the static culture group at Days Ex Vivo (DEV) 4, 7, and 14. The perfusion-cultured retinal explants exhibited reduced mRNA markers for gliosis and microglial activation, along with lower expression of GFAP and Iba1, as revealed by immunostaining. Additionally, RNA-sequencing analysis showed that perfusion culture mainly upregulated genes associated with visual perception and photoreceptor cell maintenance while downregulating the immune system process and immune response. RO-Exos promoted the uptake of PKH26-labelled exosomes and the growth of retinal explants in perfusion culture. COMPARISON WITH EXISTING METHODS: Our perfusion culture system can provide a continuous supply of culture medium to achieve steady-state equilibrium in retinal explant culture. Compared to traditional static culture, it better preserves the vitality, provides better neuroprotection, and reduces glial activation. CONCLUSIONS: This study provides a promising ex vivo model for further studies on degenerative retinal diseases and drug screening.

Study on uneven settlement and correction of steel frame structures based on numerical simulation method.

Lifting-correction is a technique to restore buildings experiencing uneven settlement, while ensuring the safety and integrity of the main structural system. This study was based on a real light-steel building structure and provided a detailed description of scenarios involving uneven settlement and the process of lifting and correction. Additionally, a sophisticated finite element (FE) model was established using the generic FE software ABAQUS, with refined material constitutive models to ensure the accuracy of simulation results. Firstly, the impact of uneven settlement on the structure was examined, including modal and stress field analyses. Different methods of breaking column (BC) and lifting column (LC) were compared and scrutinized to identify optimal approaches and minimize damage and disturbance to the building. Four methods have been proposed and compared, including simultaneously breaking columns, breaking columns with chessboard style, simultaneously lifting columns and lifting columns in multiple stages. The four methods were comprehensively evaluated from the perspectives of stress fields, displacement responses, damage and energy dissipation. The results indicated that after uneven settlement, the eigenvalues and frequencies of the structure decrease, the structure tended to be unstable. Simultaneously, as stress increases, some joints' materials enter the yielding stage, affecting the overall structural stability and safety. When damage occurs in some joints, the structural safety was compromised. The comparison between the two BC methods, including the chessboard style and simultaneously BC methods, it was revealed that the former causes less disturbance to structural initial stress field. The comparison between the two LC methods, including, simultaneously and LC in multiple stages, it was revealed that the latter performs slightly better in terms of stress fields, displacement fields, damage, energy dissipation and internal forces. Therefore, the methods of BC in chessboard style and LC in multiple stages were recommended to use in engineering practice to ensure less structural disturbance. The findings obtained from this study can provide guidance for structural engineers to solve the uneven settlement of buildings.

C-Phycocyanin Attenuates Noise-Induced Cochlear Synaptopathy via the Inhibition of Oxidative Stress and Intercellular Adhesion Molecule-1 in the Cochlea.

The synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) are the most vulnerable structures in the noise-exposed cochlea. Cochlear synaptopathy results from the disruption of these synapses following noise exposure and is considered the main cause of poor speech understanding in noisy environments, even when audiogram results are normal. Cochlear synaptopathy leads to the degeneration of SGNs if damaged IHC-SGN synapses are not promptly recovered. Oxidative stress plays a central role in the pathogenesis of cochlear synaptopathy. C-Phycocyanin (C-PC) has antioxidant and anti-inflammatory activities and is widely utilized in the food and drug industry. However, the effect of the C-PC on noise-induced cochlear damage is unknown. We first investigated the therapeutic effect of C-PC on noise-induced cochlear synaptopathy. In vitro experiments revealed that C-PC reduced the H2O2-induced generation of reactive oxygen species in HEI-OC1 auditory cells. H2O2-induced cytotoxicity in HEI-OC1 cells was reduced with C-PC treatment. After white noise exposure for 3 h at a sound pressure of 118 dB, the guinea pigs intratympanically administered 5 µg/mL C-PC exhibited greater wave I amplitudes in the auditory brainstem response, more IHC synaptic ribbons and more IHC-SGN synapses according to microscopic analysis than the saline-treated guinea pigs. Furthermore, the group treated with C-PC had less intense 4-hydroxynonenal and intercellular adhesion molecule-1 staining in the cochlea compared with the saline group. Our results suggest that C-PC improves cochlear synaptopathy by inhibiting noise-induced oxidative stress and the inflammatory response in the cochlea.

Normal Values for Atrial Deformation Measured by Feature-Tracking Cardiac MRI: A Meta-Analysis.

BACKGROUND: A consensus on normal atrial deformation measurements by feature-tracking cardiac MRI remained absent. PURPOSE: Provide reference ranges for atrial strain parameters in normal subjects, evaluating the influence of field strength and analysis software on the measurements. STUDY TYPE: Meta-analysis. POPULATION: 2708 subjects from 42 studies undergoing cardiac MRI. ASSESSMENT: A systematic search was conducted from database (PubMed, Web of Science, ScienceDirect, and EMBASE) inception through August 2023. The random-effects model was used to pool the means of biatrial strain parameters. Heterogeneity and clinical variable effects were assessed. Strain measurements among different field strengths and analysis software were compared. STATISTICAL TESTS: The inverse-variance method, Cochrane Q statistic, and I2 value, meta-regression analysis, and ANOVA were used; P < 0.05 was considered statistically significant. RESULTS: The pooled means of left atrial (LA) total strain (εs), passive strain (εe), and active strain (εa) were 37.46%, 22.73%, and 16.24%, respectively, and the pooled means of LA total strain rate (SRs), passive strain rate (SRe), and active strain rate (SRa) were 1.66, -1.95, and -1.83, indicating significant heterogeneity. The pooled means of right atrial (RA) εs, εe, and εa were 44.87%, 26.05%, and 18.83%. RA SRs, SRe, and SRa were 1.66, -1.95, and -1.83, respectively. The meta-regression identified age as significantly associated with LA εs, εe and SRe, field strength was associated with LA SRa (all P < 0.05). ANOVA revealed differences in LA εa and SRa among different analysis software and in LA εs and all LA strain rates (all P < 0.05) among field strengths. No significant differences were identified in RA strain across analysis software (RA strain: P = 0.145-0.749; RA strain rates: P = 0.073-0.744) and field strengths (RA strain: P = 0.641-0.794; RA strain rates: P = 0.204-0.458). DATA CONCLUSION: This study demonstrated the pooled reference values of biatrial strain. Age, analysis software, and field strength were attributed to differences in LA strain, whereas RA strain showed consistency across different field strengths and analysis software. Limited study subjects may account for the absence of influence on RA strain. TECHNICAL EFFICACY: Stage 5.

Two new clades recovered at high temperatures provide novel phylogenetic and genomic insights into Candidatus Accumulibacter.

Candidatus Accumulibacter, a key genus of polyphosphate-accumulating organisms, plays key roles in lab- and full-scale enhanced biological phosphorus removal (EBPR) systems. A total of 10 high-quality Ca. Accumulibacter genomes were recovered from EBPR systems operated at high temperatures, providing significantly updated phylogenetic and genomic insights into the Ca. Accumulibacter lineage. Among these genomes, clade IIF members SCELSE-3, SCELSE-4, and SCELSE-6 represent the to-date known genomes encoding a complete denitrification pathway, suggesting that Ca. Accumulibacter alone could achieve complete denitrification. Clade IIC members SSA1, SCUT-1, SCELCE-2, and SCELSE-8 lack the entire set of denitrifying genes, representing to-date known non-denitrifying Ca. Accumulibacter. A pan-genomic analysis with other Ca. Accumulibacter members suggested that all Ca. Accumulibacter likely has the potential to use dicarboxylic amino acids. Ca. Accumulibacter aalborgensis AALB and Ca. Accumulibacter affinis BAT3C720 seemed to be the only two members capable of using glucose for EBPR. A heat shock protein Hsp20 encoding gene was found exclusively in genomes recovered at high temperatures, which was absent in clades IA, IC, IG, IIA, IIB, IID, IIG, and II-I members. High transcription of this gene in clade IIC members SCUT-2 and SCUT-3 suggested its role in surviving high temperatures for Ca. Accumulibacter. Ambiguous clade identity was observed for newly recovered genomes (SCELSE-9 and SCELSE-10). Five machine learning models were developed using orthogroups as input features. Prediction results suggested that they belong to a new clade (IIK). The phylogeny of Ca. Accumulibacter was re-evaluated based on the laterally derived polyphosphokinase 2 gene, showing improved resolution in differentiating different clades.

Structure of Polysaccharide from Dendrobium nobile Lindl. and Its Mode of Action on TLR4 to Exert Immunomodulatory Effects.

Dendrobium nobile Lindl. polysaccharide (DNP1) showed good anti-inflammatory activity in our previous study. In this study, the structural characterization of DNP1 and its mode of action on TLR4 were investigated. Structural characterization suggested that DNP1 was a linear glucomannan composed of (1 → 4)-ß-Manp and (1 → 4)-ß-Glcp residues, and the acetyl group was linked to the C-2 of Manp. The possible repeating structural units of DNP1 were [→4)-2-OAc-ß-Manp-(1→]3 →4)-ß-Glcp-(1→. Surface plasmon resonance (SPR) binding test results showed that DNP1 did not bind directly to TLR4. The TLR4 and MD2 receptor blocking tests confirmed that DNP1 needs MD2 and TLR4 to participate in its anti-inflammatory effect. The binding energy of DNP1 to TLR4-MD2 was -7.9 kcal/mol, indicating that DNP1 could bind to the TLR4-MD2 complex stably. Therefore, it is concluded that DNP1 may play an immunomodulatory role by binding to the TLR4-MD2 complex and inhibiting the TLR4-MD2-mediated signaling pathway.

Video-Assisted Thoracoscopic Surgery Versus Thoracotomy Following Neoadjuvant Immunochemotherapy in Resectable Stage III Non-Small Cell Lung Cancer Among Chinese Populations: A Multi-Center Retrospective Cohort Study.

BACKGROUND: Immune checkpoint inhibitors have revolutionized non-small cell lung cancer (NSCLC) treatment but may pose greater technical challenges for surgery. This study aims to assess the feasibility and oncological effectiveness of video-assisted thoracoscopic surgery (VATS) for resectable stage III NSCLC after neoadjuvant immunochemotherapy. METHODS: Initial stage IIIA-IIIB NSCLC patients with neoadjuvant immunochemotherapy undergoing either VATS or open lobectomy at 6 medical centers during 2019-2023 were retrospectively identified. Perioperative outcomes and 2-year survival was analyzed. Propensity-score matching (PSM) was employed to balance patient baseline characteristics. RESULTS: Among the total 143 patients, PSM yielded 62 cases each for VATS and OPEN groups. Induction-related adverse events were comparable between the 2 groups. VATS showed a 14.5% conversion rate. Notably, VATS decreased numeric rating scales for postoperative pain, shortened chest tube duration (5[4-7] vs. 6[5-8] days, P = .021), reduced postoperative comorbidities (21.0% vs. 37.1%, P = .048), and dissected less N1 lymph nodes (5[4-6] vs. 7[5-9], P = .005) compared with thoracotomy. Even when converted, VATS achieves perioperative outcomes equivalent to thoracotomy. Additionally, over a median follow-up of 29.5 months, VATS and thoracotomy demonstrated comparable 2-year recurrence-free survival (77.20% vs. 73.73%, P = .640), overall survival (87.22% vs. 88.00%, P = .738), cumulative incidences of cancer-related death, and recurrence patterns. Subsequent subgroup comparisons and multivariate Cox analysis likewise revealed no statistical difference between VATS and thoracotomy. CONCLUSION: VATS is a viable and effective option for resectable stage III NSCLC patients following neoadjuvant immunochemotherapy, leading to decreased surgical-related pain, earlier chest tube removal, reduced postoperative complications, and similar survival outcomes compared to thoracotomy.

GLP-1 receptor agonists and myocardial metabolism in atrial fibrillation.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Many medical conditions, including hypertension, diabetes, obesity, sleep apnea, and heart failure (HF), increase the risk for AF. Cardiomyocytes have unique metabolic characteristics to maintain adenosine triphosphate production. Significant changes occur in myocardial metabolism in AF. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been used to control blood glucose fluctuations and weight in the treatment of type 2 diabetes mellitus (T2DM) and obesity. GLP-1RAs have also been shown to reduce oxidative stress, inflammation, autonomic nervous system modulation, and mitochondrial function. This article reviews the changes in metabolic characteristics in cardiomyocytes in AF. Although the clinical trial outcomes are unsatisfactory, the findings demonstrate that GLP-1 RAs can improve myocardial metabolism in the presence of various risk factors, lowering the incidence of AF.

Relating the carbon sources to denitrifying community in full-scale wastewater treatment plants.

Carbon source is a key factor determining the denitrifying effectiveness and efficiency in wastewater treatment plants (WWTPs). Whereas, the relationships between diverse and distinct denitrifying communities and their favorable carbon sources in full-scale WWTPs were not well-understood. This study performed a systematic analysis of the relationships between the denitrifying community and carbon sources by using 15 organic compounds from four categories and activated sludge from 8 full-scale WWTPs. Results showed that, diverse denitrifying bacteria were detected with distinct relative abundances in 8 WWTPs, such as Haliangium (1.98-4.08%), Dechloromonas (2.00-3.01%), Thauera (0.16-1.06%), Zoogloea (0.09-0.43%), and Rhodoferax (0.002-0.104%). Overall, acetate resulted in the highest denitrifying activities (1.21 to 4.62 mg/L/h/gMLSS), followed by other organic acids (propionate, butyrate and lactate, etc.). Detectable dissimilatory nitrate reduction to ammonium (DNRA) was observed for all 15 carbon sources. Methanol and glycerol resulted in the highest DRNA. Acetate, butyrate, and lactate resulted in the lowest DNRA. Redundancy analysis and 16S cDNA amplicon sequencing suggested that carbon sources within the same category tended to correlate to similar denitrifiers. Methanol and ethanol were primarily correlated to Haliangium. Glycerol and amino acids (glutamate and aspartate) were correlated to Inhella and Sphaerotilus. Acetate, propionate, and butyrate were positively correlated to a wide range of denitrifiers, explaining the high efficiency of these carbon sources. Additionally, even within the same genus, different amplicon sequence variants (ASVs) performed distinctly in terms of carbon source preference and denitrifying capabilities. These findings are expected to benefit carbon source formulation and selection in WWTPs.

Sex-specific ventricular morphology, function, and tissue characteristics in arterial hypertension: a magnetic resonance study of the Hamburg city health cohort.

OBJECTIVE: To determine the influence of arterial hypertension (AHT), sex, and the interaction between both left- and right ventricular (LV, RV) morphology, function, and tissue characteristics. METHODS: The Hamburg City Health Study (HCHS) is a population-based, prospective, monocentric study. 1972 individuals without a history of cardiac diseases/ interventions underwent 3 T cardiac MR imaging (CMR). Generalized linear models were conducted, including AHT, sex (and the interaction if significant), age, body mass index, place of birth, diabetes mellitus, smoking, hyperlipoproteinemia, atrial fibrillation, and medication. RESULTS: Of 1972 subjects, 68% suffered from AHT. 42% with AHT and 49% controls were female. Females overall showed a higher ejection fraction (EF) (LV: regression coefficient +2.4% [95% confidence interval: 1.7; 3.1]), lower volumes and LV mass (-19.8% [-21.3; -18.5]), and prolonged native septal T1 (+22.1 ms [18.3; 25.9])/T2 relaxation times (+1.1 ms [0.9; 1.3]) (all p < 0.001) compared to males. Subjects with AHT showed a higher EF (LV: +1.2% [0.3; 2.0], p = 0.009) and LV mass (+6.6% [4.3; 9.0], p < 0.001) than controls. The interaction between sex and AHT influenced mapping. After excluding segments with LGE, males (-0.7 ms [-1.0; -0.3 | ) and females with AHT (-1.1 ms [-1.6; -0.6]) showed shorter T2 relaxation times than the sex-respective controls (p < 0.001), but the effect was stronger in females. CONCLUSION: In the HCHS, female and male subjects with AHT likewise showed a higher EF and LV mass than controls, independent of sex. However, differences in tissue characteristics between subjects with AHT and controls appeared to be sex-specific. CLINICAL RELEVANCE STATEMENT: The interaction between sex and cardiac risk factors is an underestimated factor that should be considered when comparing tissue characteristics between hypertensive subjects and controls, and when establishing cut-off values for normal and pathological relaxation times. KEY POINTS: There are sex-dependent differences in arterial hypertension, but it is unclear if cardiac MR parameters are sex-specific. Differences in cardiac MR parameters between hypertensive subjects and healthy controls appeared to be sex-specific for tissue characteristics. Sex needs to be considered when comparing tissue characteristics in patients with arterial hypertension to healthy controls.

An Audio-Visual Speech Separation Model Inspired by Cortico-Thalamo-Cortical Circuits.

Audio-visual approaches involving visual inputs have laid the foundation for recent progress in speech separation. However, the optimization of the concurrent usage of auditory and visual inputs is still an active research area. Inspired by the cortico-thalamo-cortical circuit, in which the sensory processing mechanisms of different modalities modulate one another via the non-lemniscal sensory thalamus, we propose a novel cortico-thalamo-cortical neural network (CTCNet) for audio-visual speech separation (AVSS). First, the CTCNet learns hierarchical auditory and visual representations in a bottom-up manner in separate auditory and visual subnetworks, mimicking the functions of the auditory and visual cortical areas. Then, inspired by the large number of connections between cortical regions and the thalamus, the model fuses the auditory and visual information in a thalamic subnetwork through top-down connections. Finally, the model transmits this fused information back to the auditory and visual subnetworks, and the above process is repeated several times. The results of experiments on three speech separation benchmark datasets show that CTCNet remarkably outperforms existing AVSS methods with considerably fewer parameters. These results suggest that mimicking the anatomical connectome of the mammalian brain has great potential for advancing the development of deep neural networks.

Identification and Molecular Mechanism of Novel Two-Way Immunomodulatory Peptides from Ovalbumin: In Vitro Cell Experiments, De Novo Sequencing, and Molecular Docking.

The purpose of this study was to identify ovalbumin-derived immunomodulatory peptides by in vitro cell experiments, de novo sequencing, and molecular docking. Ovalbumin hydrolysates were prepared by two enzymes (alkaline protease and papain) individually, sequentially, or simultaneously, respectively. The simultaneous enzymatic hydrolysate (OVAH) had a high degree of hydrolysis (38.12 ± 0.48%) and exhibited immune-enhancing and anti-inflammatory activities. A total of 160 peptides were identified by LC-MS/MS in OVAH. Three novel peptides NVMEERKIK, ADQARELINS, and WEKAFKDE bound to TLR4-MD2 through hydrogen bonds and hydrophobic interactions with high binding affinity and binding energies of -181.40, -178.03, and -168.12 kcal/mol, respectively. These three peptides were synthesized and validated for two-way immunomodulatory activity. NVMEERKIK exhibiting the strongest immunomodulatory activity, increased NO and TNF-α levels by 128.69 and 38.01%, respectively, in normal RAW264.7 cells and reduced NO and TNF-α levels by 27.31 and 39.13%, respectively, in lipopolysaccharide-induced inflammatory RAW264.7 cells. Overall, this study first revealed that ovalbumin could be used as an immunomodulatory source for controlling inflammatory factor secretion.

The NEDD8 activating enzyme inhibitor MLN4924 mitigates doxorubicin-induced cardiotoxicity in mice.

Doxorubicin (DOX) is a widely utilized chemotherapeutic agent in clinical oncology for treating various cancers. However, its clinical use is constrained by its significant side effects. Among these, the development of cardiomyopathy, characterized by cardiac remodeling and eventual heart failure, stands as a major concern following DOX chemotherapy. In our current investigation, we have showcased the efficacy of MLN4924 in mitigating doxorubicin-induced cardiotoxicity through direct inhibition of the NEDD8-activating enzyme, NAE. MLN4924 demonstrated the ability to stabilize mitochondrial function post-doxorubicin treatment, diminish cardiomyocyte apoptosis, alleviate oxidative stress-induced damage in the myocardium, enhance cardiac contractile function, mitigate cardiac fibrosis, and impede cardiac remodeling associated with heart failure. At the mechanistic level, MLN4924 intervened in the neddylation process by inhibiting the NEDD8 activating enzyme, NAE, within the murine cardiac tissue subsequent to doxorubicin treatment. This intervention resulted in the suppression of NEDD8 protein expression, reduction in neddylation activity, and consequential manifestation of cardioprotective effects. Collectively, our findings posit MLN4924 as a potential therapeutic avenue for mitigating doxorubicin-induced cardiotoxicity by attenuating heightened neddylation activity through NAE inhibition, thereby offering a viable and promising treatment modality for afflicted patients.

Broadband Room-Temperature Photodetection via InBiTe3 Nanosheet.

Broadband room-temperature photodetection has become a pressing need as application requirements for communication, imaging, spectroscopy, and sensing have evolved. Topological insulators (TIs) have narrow bandgap structures with a wide absorption spectral response range, which should meet the requirements of broadband detection. However, owing to their high carrier concentration and low carrier mobility resulting in poor noise equivalent power (NEP), they are generally considered unsuitable for photodetection. Here, InBiTe3 alloy nanosheet formed by doping In2Te3 into Bi2Te3(≈ 1:1) is utilized, effectively improving carrier mobility by over ten times while maintaining a narrow bandgap structure, to fabricate a broadband photodetector covering a wide response range from visible to millimeter wave (MMW). Under the synergistic multi-mechanism of the photoelectric effect in the visible-infrared region and the electromagnetic-induced potential well (EIW) effect in Terahertz band, the performance of NEP = 75 pW Hz-1/2 and response time τ ≈100 µs in visible to infrared band and the performance of NEP = 6.7 × 10-3 pW Hz-1/2, τ ≈8 µs in Terahertz region are achieved. The results demonstrate the promising prospects of topological insulator alloy (like InBiTe3) nanosheet in optoelectronic detection applications and provide a direction for the research into high-performance broadband photoelectric detectors via TIs.

Activation Mechanism of Fe2+ in Pyrrhotite Flotation: Microflotation and DFT Calculations.

In industrial manufacturing, pyrrhotite(Fe1-xS), once depressed, is commonly activated for flotation. However, the replacement of CuSO4 is necessary due to the need for exact control over the dosage during the activation of pyrrhotite, which can pose challenges in industrial settings. This research introduces the use of FeSO4 for the first time to efficiently activate pyrrhotite. The impact of two different activators on pyrrhotite was examined through microflotation experiments and density functional theory (DFT) calculations. Microflotation experiments confirmed that as the CuSO4 dosage increased from 0 to 8 × 10-4 mol/L, the recovery of pyrrhotite initially increased slightly from 71.27% to 87.65% but then sharply decreased to 16.47%. Conversely, when the FeSO4 dosage was increased from 0 to 8 × 10-4 mol/L, pyrrhotite's recovery rose from 71.27% to 82.37%. These results indicate a higher sensitivity of CuSO4 to dosage variations, suggesting that minor alterations in dosage can significantly impact its efficacy under certain experimental conditions. In contrast, FeSO4 might demonstrate reduced sensitivity to changes in dosage, leading to more consistent performance. Fe ions can chemically adsorb onto the surface of pyrrhotite (001), creating a stable chemical bond, thereby markedly activating pyrrhotite. The addition of butyl xanthate (BX), coupled with the action of Fe2+ on activated pyrrhotite, results in the formation of four Fe-S bonds on Fe2+. The proximity of their atomic distances contributes to the development of a stable double-chelate structure. The S 3p orbital on BX hybridizes with the Fe 3d orbital on pyrrhotite, but the hybrid effect of Fe2+ activation is stronger than that of nonactivation. In addition, the Fe-S bond formed by the addition of activated Fe2+ has a higher Mulliken population, more charge overlap, and stronger covalent bonds. Therefore, Fe2+ is an excellent, efficient, and stable pyrrhotite activator.

Evaluation of nanoparticle albumin-bound paclitaxel loaded macrophages for glioblastoma treatment based on a microfluidic chip.

Introduction: Glioblastoma (GBM) is a primary brain malignancy with a dismal prognosis and remains incurable at present. In this study, macrophages (MΦ) were developed to carry nanoparticle albumin-bound paclitaxel (nab-PTX) to form nab-PTX/MΦ. The aim of this study is to use a GBM-on-a-chip to evaluate the anti-GBM effects of nab-PTX/MΦ. Methods: In this study, we constructed nab-PTX/MΦ by incubating live MΦ with nab-PTX. We developed a microfluidic chip to co-culture GBM cells and human umbilical vein endothelial cells, mimicking the simplified blood-brain barrier and GBM. Using a syringe pump, we perform sustainable perfusion of nutrient media. To evaluate the anti-GBM effects nab-PTX/MΦ, we treated the GBM-on-a-chip model with nab-PTX/MΦ and investigated GBM cell proliferation, migration, and spheroid formation. Results: At the chosen concentration, nab-PTX did not significantly affect the viability, chemotaxis and migration of MΦ. The uptake of nab-PTX by MΦ occurred within 1 h of incubation and almost reached saturation at 6 h. Additionally, nab-PTX/MΦ exhibited the M1 phenotype, which inhibits tumor progression. Following phagocytosis, MΦ were able to release nab-PTX, and the release of nab-PTX by MΦ had nearly reached its limit at 48 h. Compared with control group and blank MΦ group, individual nab-PTX group and nab-PTX/MΦ group could inhibit tumor proliferation, invasion and spheroid formation. Meanwhile, the anti-GBM effect of nab-PTX/MΦ was more significant than nab-PTX. Discussion: Our findings demonstrate that nab-PTX/MΦ has a significant anti-GBM effect compared to individual nab-PTX or MΦ administration, suggesting MΦ as potential drug delivery vectors for GBM therapy. Furthermore, the developed GBM-on-a-chip model provides a potential ex vivo platform for innovative cell-based therapies and tailored therapeutic strategies for GBM.

Key points for protecting the external branch of the superior laryngeal nerve in open thyroidectomy: A possible exploration technique.

OBJECTIVE: Injury of the external branch of the superior laryngeal nerve (EBSLN) is easily overlooked in thyroidectomy, and voice changes caused by the injury have a negative effect on an increasing number of patients. This study aimed to reduce the injury rate of EBSLN by expanding the sternothyroid-laryngeal triangle and standardizing the exploration procedure. METHODS: A total of 520 patients who had undergone thyroidectomy at the First Affiliated Hospital of Nanchang University between September 2021 and April 2022 were analyzed. During the operation, the exposure rate of the EBSLN before and after sternothyroid-laryngeal triangle expansion was compared, and all EBSLNs were anatomically classified. RESULTS: The exposure rate of EBSLN after sternothyroid-laryngeal triangle expansion reached 82.7%, which is much higher than that before sternothyroid-laryngeal triangle expansion (33.7%), and voice change caused by injury of the EBSLN was reported in one case (the injury rate was 0.2%). The classification and proportion of the EBSLN were as follows: Type 1 (55.3%), the nerve ran within 1 cm above the STP, but no coincidence or crossover with blood vessels was observed in this region; Type 2 (14.7%), the nerve travelled within 1 cm above the STP and overlapped or intersected with blood vessels in this region; Type 3 (12.7%), the EBSLN ran below the level of the STP; and Type 4 (17.3%), no EBSLN was observed within 1 cm above the STP. CONCLUSION: In thyroidectomy, injury to the EBSLN can be effectively reduced by expanding the sternothyroid-laryngeal triangle and exploring the upper pole area of the thyroid as far as possible, which has great clinical significance in reducing postoperative voice box injury.

Analysis of Polarization Angle on Holographic Recording Based on PQ/PMMA.

The polarization state of light waves significantly affects the quality of holographic recordings. This paper quantitatively analyzes the impact of different polarization states of signal and reference beams on the quality of holographic recordings in PQ/PMMA photopolymer systems during the holography process. By deriving the light field distribution of the interference between two light waves of different polarization states and introducing the interference fringe contrast and the modulation of the refractive index of the photopolymer, we established the relationship between the diffraction efficiency of PQ/PMMA photopolymer holographic gratings and the angle between polarization directions. Based on this relationship, simulations and experiments were conducted. The experimental results demonstrated that as the angle between the polarization directions increased, the diffraction efficiency of the material decreased, with the efficiency dropping to 24.69% of its original value when the angle increased from 0° to 50°. When the angle increased to 60°, the influence of polarization characteristics became gradually significant, and at 90°, it was entirely dominated by polarization characteristics. The photoinduced birefringence properties of the PQ/PMMA prepared in the measurement experiment were studied, and the polarization characteristics of the reconstructed light under polarization direction angles of 0°, 60°, and 90° were investigated. The results indicated that at a polarization direction angle of 60 degrees, the material exhibited a significant response to the polarization information of the signal light. Finally, holographic recordings of objects at different polarization direction angles were conducted, and the reconstructed images were used to visually reflect the impact of the polarization direction angle on the quality of holographic recordings.

Advances in self-assembled nanotechnology in tumor therapy.

The emergence of nanotechnology has opened up a new way for tumor therapy. Among them, self-assembled nanotechnology has received extensive attention in medicine due to its simple preparation process, high drug-loading capacity, low toxicity, and low cost. This review mainly summarizes the preparation methods of self-assembled nano-delivery systems, as well as the self-assembled mechanism of carrier-free nanomedicine, polymer-carried nanomedicine, polypeptide, and metal drugs, and their applications in tumor therapy. In addition, we discuss the advantages and disadvantages, future challenges, and opportunities of these self-assembled nanomedicines, which provide important references for the development and application of self-assembled nanotechnology in the field of medical therapy.

Astragaloside IV ameliorates cisplatin-induced liver injury by modulating ferroptosis-dependent pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: The use of antineoplastic drugs, such as cisplatin, in clinical practice can cause adverse effects in patients, such as liver injury, which limits their long-term use. Therefore, there is an urgent need to develop alternative therapeutic strategies or drugs to minimize cisplatin-induced liver injury. Huangqi, the root of Astragalus membranaceus, is extensively used in traditional Chinese medicine (TCM) and has been employed in treating diverse liver injuries. Astragalus membranaceus contains several bioactive constituents, including triterpenoid saponins, one of which, astragaloside IV (ASIV), has been reported to have anti-inflammatory and antioxidant stress properties. However, its potential in ameliorating cisplatin-induced liver injury has not been explored. AIM OF THE STUDY: The objective of this study was to examine the mechanism by which ASIV protects against cisplatin-induced liver injury. MATERIALS AND METHODS: This study established a model of cisplatin-induced liver injury in mice, followed by treatment with various doses of astragaloside IV (40 mg/kg, 80 mg/kg). In addition, a model of hepatocyte ferroptosis in AML-12 cells was established using RSL3. The mechanism of action of astragaloside IV was investigated using a range of methods, including Western blot assay, qPCR, immunofluorescence, histochemistry, molecular docking, and high-content imaging system. RESULTS: The findings suggested a significant improvement in hepatic injury, inflammation and oxidative stress phenotypes with the administration of ASIV. Furthermore, network pharmacological analyses provided evidence that a major pathway for ASIV to attenuate cisplatin-induced hepatic injury entailed the cell death cascade pathway. It was observed that ASIV effectively inhibited ferroptosis both in vivo and in vitro. Subsequent experimental outcomes provided further validation of ASIV's ability to hinder ferroptosis through the inhibition of PPARα/FSP1 signaling pathway. The current findings suggest that ASIV could function as a promising phytotherapy composition to alleviate cisplatin-induced liver injury. CONCLUSIONS: The current findings suggest that astragaloside IV could function as a promising phytotherapy composition to alleviate cisplatin-induced liver injury.