Unintentional emissions of polychlorinated naphthalenes in China: Sources, composition, and historical trends.

Polychlorinated naphthalenes (PCNs) are detrimental to human health and the environment. With the commercial production of PCNs banned, unintentional releases have emerged as a significant environmental source. However, relevant information is still scarce. In this study, provincial emissions for eight PCNs homologues from 37 sources in the Chinese mainland during the period of 1960-2019 were estimated based on a source-specific and time-varying emission factor database. The results showed that the total PCNs emissions in 2019 reached 757.0 kg with Hebei ranked at the top among all the provinces and iron & steel industry as the biggest source. Low-chlorinated PCNs comprised 90% of emissions by mass, while highly chlorinated PCNs dominated in terms of toxicity, highlighting divergent priorities for mitigating emissions and safeguarding human health. The emissions showed an overall upward trend from 1960 to 2019 driven by emission increase from iron & steel industry in terms of source, and from North China and East China in terms of geographic area. Per-capita emissions followed an inverted U-shaped environmental Kuznets curve while emission intensities decreased with increasing per-capita Gross Domestic Product (GDP) following a nearly linear pattern when log-transformed.

Unidirectional self-imaging in multiple shifted photonic crystal interfaces.

In this study, we investigate the unidirectional self-imaging phenomenon in the shifted photonic crystal (PC) heterostructure. A spin-locked topological edge state, which originates from the mismatch of the Wannier center positions, can propagate along the shifted PC interface without backscattering. When the neighboring shifted PC interfaces are close enough, the coupling between the edge states happens, and coupled edge states (CES) can be found. Based on the finite element method (FEM) simulation, the spin-locked multimode interference (MMI) and self-imaging phenomenon of CES, including paired and symmetrical interference, are achieved in multiple shifted PC interfaces. To illustrate the application of the frequency splitters, the T-shaped and double cross-shaped structures with backscattering immunity and spin-locked characteristics are proposed. Our work provides an alternative way toward the design of a topological splitter by utilizing the photonic frequency and spin degrees of freedom at the same time.

Size Uniformity of CsPbBr3 Perovskite Quantum Dots via Manganese-Doping.

The achievement of size uniformity and monodispersity in perovskite quantum dots (QDs) requires the implementation of precise temperature control and the establishment of optimal reaction conditions. Nevertheless, the accurate control of a range of reaction variables represents a considerable challenge. This study addresses the aforementioned challenge by employing manganese (Mn) doping to achieve size uniformity in CsPbBr3 perovskite QDs without the necessity for the precise control of the reaction conditions. By optimizing the Mn:Pb ratio, it is possible to successfully dope CsPbBr3 QDs with the appropriate concentrations of Mn²âº and achieve a uniform size distribution. The spectroscopic measurements on single QDs indicate that the appropriate Mn²âº concentrations can result in a narrower spectral linewidth, a longer photoluminescence (PL) lifetime, and a reduced biexciton Auger recombination rate, thus positively affecting the PL properties. This study not only simplifies the size control of perovskite QDs but also demonstrates the potential of Mn-doped CsPbBr3 QDs for narrow-linewidth light-emitting diode applications.

Association between thymus density loss and efficacy in non-small cell lung cancer patients treated with immune checkpoint inhibitors.

Background: Although the thymus undergoes degeneration with the advancement of age, recent studies have continuously revealed that the thymus possesses the potential for regeneration and may reverse this aging trend. Furthermore, an increasing number of studies indicate an association between thymus function and immunotherapy. Considering that lung cancer patients typically undergo chest computed tomography (CT) scans during treatment, this provides convenient conditions for us to observe thymic remodeling through imaging data. Therefore, exploring the changes in the thymus on CT images is of great significance for understanding its relationship with the efficacy of immunotherapy in non-small cell lung cancer (NSCLC) patients. This study investigated the CT imaging characteristics of thymic density changes in patients with advanced NSCLC after immunotherapy. The primary objective was to determine whether changes in thymic density are predictors of response to immunotherapy in patients with NSCLC. Methods: A total of 412 patients with advanced NSCLC who underwent immunotherapy were included. Thymic density measurements were taken initially and after immunotherapy, with the annualized change calculated. Comprehensive analysis, including disease progression, survival, and subgroup assessments, was conducted. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR). Results: The annual change in density of the thymic region ranged from -108 to 108 HU after the initiation of ICIs. Patients were categorized into "loss" or "non-loss" groups (210 vs. 202) based on thymic density changes. Analysis of short-term progression of solid tumors revealed no statistically significant differences in ORR (P=0.55) and DCR (P=0.67) between the two groups. Throughout the entire follow-up period, 41 patients (19.5%) in the "loss" group and 64 patients (31.7%) in the "non-loss" group died. Thymic density reduction was not associated with PFS (P=0.08), but it was positively associated with increased OS (P=0.003). The results were consistent across subgroups. Conclusions: Thymic density changes were observed in nearly all NSCLC patients undergoing immunotherapy, with decreased density associated with longer OS. These findings suggest a potential association between thymic density changes and immune efficacy in NSCLC immunotherapy.

Development of prognostic model incorporating a ferroptosis/cuproptosis-related signature and mutational landscape analysis in muscle-invasive bladder cancer.

BACKGROUND: Muscle-invasive bladder cancer (MIBC) is a prevalent and aggressive malignancy. Ferroptosis and cuproptosis are recently discovered forms of programmed cell death (PCD) that have attracted much attention. However, their interactions and impacts on MIBC overall survival (OS) and treatment outcomes remain unclear. METHODS: Data from the TCGA-BLCA project (as the training set), cBioPortal database, and GEO datasets (GSE13507 and GSE32894, as the test sets) were utilized to identify hub ferroptosis/cuproptosis-related genes (FRGs and CRGs) and develop a prognostic signature. Differential expression analysis (DEA) was conducted, followed by univariate and multivariate Cox's regression analyses and multiple machine learning (ML) techniques to select genetic features. The performance of the ferroptosis/cuproptosis-related signature was evaluated using Kaplan-Meier (K-M) survival analysis and receiver-operating characteristics (ROC) curves. Mutational and tumour immune microenvironment landscapes were also explored. Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) experiments confirmed the expression patterns of the hub genes, and functional assays assessed the effects of SCD knockdown on cell viability, proliferation, and migration. RESULTS: DEA revealed dysregulated FRGs and CRGs in the TCGA MIBC cohort. SCD, DDR2, and MT1A were identified as hub genes. A prognostic signature based on the sum of the weighted expression of these genes demonstrated strong predictive efficacy in the training and test sets. Nomogram incorporating this signature accurately predicted 1-, 3-, and 5-year survival probabilities in the TCGA cohort and GSE13507 dataset. Copy number variation (CNV) and tumour immune microenvironment analysis revealed that high risk score level groups were associated with immunosuppression and lower tumour purity. The associations of risk scores with immunotherapy and chemical drugs were also explored, indicating their potential for guiding treatment for MIBC patients. The dysregulated expression patterns of three hub genes were validated by RT-qPCR experiments. CONCLUSIONS: Targeting hub FRGs and CRGs could be a promising therapeutic approach for MIBC. Our prognostic model offers a new framework for MIBC subtyping and can inform personalized therapeutic strategies.

Integrated analysis of disulfidoptosis-related genes identifies NRP1 as a novel biomarker promoting proliferation of gastric cancer via glutamine mediated energy metabolism.

The incidence and mortality of gastric cancer rank fifth and fourth worldwide among all malignancies, respectively. Additionally, disulfidoptosis, a recently identified form of cellular demise, is closely linked to the initiation and advancement of malignancies. This study aims to create a novel signature of disulfidptosis-related genes (DRGs) and to further explore its association with the tumor immune microenvironment. Based on our comprehensive study, a prognostic signature consisting of 31 DRGs in stomach adenocarcinoma (STAD) was identified and characterized. Through the integrative analyses involving gene expression profiling, machine learning algorithms, and Cox regression models, the prognostic significance of these DRGs was demonstrated. Our findings highlight their strong predictive power in assessing overall survival across diverse patient datasets, and their better performance than traditional clinicopathological factors. Moreover, the DRGs signature showed association with the characteristics of the tumor microenvironment, which has implications for the immune modulation and therapeutic strategies in STAD. Specifically, NRP1 emerged as a key DRG with elevated expression in STAD, showing correlation with the advanced stages of diseases and poorer outcomes. Functional studies further revealed the role of NRP1 in promoting STAD cell proliferation through the modulation of glutamine metabolism. Overall, our study underscores the clinical relevance of DRGs as biomarker and potential therapeutic targets in STAD management, providing insights into disease biology and personalized treatments.

Bio-derived Schiff base vitrimer with outstanding flame retardancy, toughness, antibacterial, dielectric and recycling properties.

Thermosetting resins are widely used in high-tech applications for excellent mechanical robustness and chemical resistance. With increasing attention to the environmental and usage safety issues, it is necessary to develop bio-derived, recyclable, tough, and fire-retardant thermosetting resins. Herein, a high-performance, vanillin-based vitrimer (CIP1.0) was prepared. The CIP1.0 with 1.0 wt% phosphorus passes vertical burning (UL-94) V-0 rating with a limiting oxygen index (LOI) of 27.2%. The phosphorus-containing and Schiff base groups act synergistically in gas and condensed phases during combustion, endowing CIP1.0 with outstanding fire retardancy. The CIP1.0 shows excellent toughness with high elongation at break of 45.0% due to the π-π stacking of numerous rigid aromatic groups and appropriate cross-linking density. The highly symmetrical structure and low polarizability of CIP1.0 result in a low dielectric constant. The CIP1.0 exhibits superior antimicrobial properties. The CIP1.0 can be reprocessed by hot-pressing at 140 °C for 10 min. The non-destructive, closed-loop recycling of carbon fibers in the carbon fiber-reinforced CIP1.0 composite can be achieved under mild conditions due to the degradable Schiff base groups of CIP1.0. In this work, a bio-derived, tough, fire-retardant, low dielectric, and antimicrobial vitrimer is prepared to provide a rational strategy for the design of advanced environmentally friendly thermosetting resins.

Study on the precursory characteristics and influencing factors of rockburst in the bifurcation area of coal seam.

To explore the precursory characteristics and influencing factors of rockburst in the bifurcation area of coal seam, the evolution and expansion of fracture and the energy accumulation and dissipation characteristics of coal-rock parting-coal structure (CRCS) during failure and instability process are explored from a micro-scopic perspective, and the influence of coal and rock parting parameters on the instability is studied. The following four points are addressed: (1) Compared with the single coal structure or the coal- rock combined structure, the CRCS can more directly reflect the geological structure characteristics of the coal seam in the bifurcated area; (2) The failure and instability process of CRCS includes two types of instability: slip and fracture. The slip instability is characterized by low strength and high energy release, which is very difficult to predict. (3) Before the failure of CRCS, there are several precursor signal characteristics, such as the shortened development time of the "stable-fracture-stable" cycle, abnormal slip dislocation of the contact surface, and rapid accumulation of rock fracture energy. (4) The inclination angle of the contact surface affects the instability form, the strength of the rock parting affects the instability state, and the thickness of the rock parting affects the impact tendency. The research results have important theoretical significance for preventing rockburst caused by failure and instability in bifurcated area of coal seam.

Role of primary drivers leading to emission reduction of major air pollutants and CO2 from global power plants.

Electricity production is a significant source of air pollution. Various factors, including electricity demand, generation efficiency, energy mix, and end-of-pipe control measures, are responsible for the emission changes during electricity generation. Although electricity production more than doubled from 1990 to 2017, air pollutant emissions showed a moderate increase or decrease, which was attributed to mitigating drivers such as increased clean energy use, improved power generation efficiency, and widespread installation of end-of-pipe control facilities. The absence of these mitigating drivers would have increased CO2, fine particulate matter (PM2.5), black carbon, SO2, and NOx emissions in 2017 by 165 %, 403 %, 1070 %, 614 %, and 274 % than their actual levels, respectively. The improved electricity generation efficiency reduced potential CO2, PM2.5, SO2, and NOx emissions by 30 %, 295 %, 119 %, and 52 % compared to actual emissions, respectively. Meanwhile, the installation of end-of-pipe facilities reduced potential SO2 and PM2.5 emissions by 34.7 and 4.0 Tg, respectively. Considerable differences in emissions among countries were found to be attributable to their differences in electricity demand and the implementation of local mitigating polices.

Perianal embryonal rhabdomyosarcoma: A case report.

Perianal embryonal rhabdomyosarcoma (ERMS) is a rare disease with a poor prognosis. There are few reported cases of this disease, and specific clinical manifestations are lacking; therefore, making an early diagnosis before surgery is challenging. In November 2014, a 30-year-old man was admitted to Xiaoshan Affiliated Hospital of Wenzhou Medical University due to severe left perianal pain. Ultrasonography revealed a multilocular perianal abscess, and an emergency perianal abscess incision and drainage were performed. However, pathology combined with immunohistochemistry confirmed an ERMS. The patient did not receive postoperative radiotherapy or chemotherapy and died of multiple metastases and multiple organ failure 6 months later. Perianal ERMS is highly malignant and rare, and can easily be misdiagnosed as a perianal abscess. Clinicians must enhance their knowledge and improve preoperative diagnostic tests to prevent misdiagnoses.

Expressions and clinical significance of CCN5 and E-cadherin in primary and recurrent lesions of breast cancer.

Background: Breast cancer recurrence and lymph node metastasis significantly impact patient outcomes. Understanding the molecular mechanisms behind these processes is crucial for developing effective treatments. CCN5 and E-cadherin are proteins involved in cell adhesion and epithelial-mesenchymal transition (EMT), playing roles in breast cancer progression. Objective: This study aimed to analyze the expression levels and clinical significance of CCN5 and E-cadherin in primary and recurrent breast cancer lesions. Methods: Immunohistochemical staining using the SP method was performed to detect CCN5 and E-cadherin expression levels in 28 normal breast tissue samples, 52 primary breast cancer lesions, and paired recurrent chest wall lesions. The expression levels of these proteins were compared across different tissue types and correlated with lymph node metastasis. Results: CCN5 and E-cadherin expression levels significantly differed among normal breast tissues, primary breast cancer lesions, and recurrent lesions (Χ2 = 18.934 and Χ2 = 14.516, p < 0.05). Primary breast cancer lesions exhibited higher CCN5 and E-cadherin expression levels compared with recurrent lesions and normal tissues, although these differences were not statistically significant. Patients without lymph node metastases exhibited significantly higher expression levels of CCN5 and E-cadherin compared with those with lymph node metastases (Χ2 = 9.775, Χ2 = 9.1479, p < 0.05). A positive correlation between CCN5 and E-cadherin expression levels was found in breast cancer tissues (r = 0.398, p < 0.001). Conclusion: CCN5 and E-cadherin were expressed at lower levels in recurrent breast cancer tissues and those with lymph node metastases, indicating their potential roles in breast cancer recurrence and metastasis. These findings suggest that CCN5 and E-cadherin might work synergistically to influence breast cancer progression.

Antibacterial and antioxidant phlorizin-loaded nanofiber film effectively promotes the healing of burn wounds.

Burns usually result in damage and loss of skin forming irregular wound wounds. The lack of skin tissue protection makes the wound site highly vulnerable to bacterial infections, hindering the healing process. However, commonly used wound dressings do not readily provide complete coverage of irregular wounds compared to regular wounds. Therefore, there is an urgent need to prepare a wound dressing with high antimicrobial efficacy for the administration of drugs to irregular wounds. In this study, a chitosan (CS)/polyvinylpyrrolidone (PVP) composite nanofiber membrane (CS/PVP/Phlorizin) loaded with root bark glycosides (Phlorizin) was developed using an electrostatic spinning technique. The incorporation of phlorizin, a natural antioxidant, into the fiber membranes notably boosted their antimicrobial and antioxidant capabilities, along with demonstrating excellent hydrophilic characteristics. In vitro cellular experiments showed that CS/PVP/Phlorizin increased Hacat cell viability with the presence of better cytocompatibility. In scald wound healing experiments, Phlorizin-loaded nanofibrous membranes significantly promoted re-epithelialization and angiogenesis at the wound site, and reduced the inflammatory response at the wound site. Therefore, the above results indicate that this nanofiber membrane is expected to be an ideal dressing for burn wounds.

Embryo thermal manipulation modifies development and hepatic lipid metabolism in post-hatch layer-type chicks.

Incubation temperature is a crucial environmental factor affecting embryonic development and chick quality. Metabolism during the embryonic stage, particularly liver lipid metabolism, is essential for the growth and development of poultry. This study aimed to investigate the effects of embryo thermal manipulation with high (TMH, 39.5°C, 65% RH, 8 h/d) and low (TML, 20°C, 65% RH, 1 h/d) temperatures during 8-15th embryonic age on hatching performance and liver lipid metabolism in layer chicks. Additionally, the duration of TM effects was evaluated through a short-term feeding trial. The results indicated that TMH accelerated the hatching process without significantly affecting hatchability and growth performance. In contrast, TML delayed hatching time and significantly reduced hatchability and chick quality. After hatching, TML also increased residual yolk weight and reduced the relative liver weight in relation to body weight (BW) and yolk-free body mass (YFBM). Moreover, lipid droplets in the liver were stained with Oil Red O, and the lipid content in the liver and serum was further detected. TMH had no significant impact on triglyceride (TG) and total cholesterol (TCHO) content in the liver and serum, but upregulated the expression of lipogenesis-related genes ACC, Fas, and Fatp1 compared to the TML group. Conversely, TML significantly reduced liver TG content, enhanced lipoprotein lipase (LPL) activity, and promoted the expression of lipid oxidation-related genes CPT-1, PGC-1α, and PPARα. At 7 d of age, liver LPL activity was significantly increased in the TMH group. However, there were no significant changes in the content of TG and TCHO in the liver and the expression of lipid metabolism-related genes in the TML group. Overall, these results indicate that embryonic thermal manipulation alters hatching performance and liver lipid metabolism in layer chicks. TML reduces TG content by increasing liver lipid oxidation capacity. However, this effect is not long-lasting, as the influence of TM diminishes as the chicks develop.

Identification of Immune Gene Signature Associated with T Cells and Natural Killer Cells in Type 1 Diabetes.

Purpose: This study aimed to investigate the abnormal infiltration of immune cells in type 1 diabetes mellitus (T1D) and elucidate their regulatory mechanisms. Methods: Public T1D-related gene expression data were obtained from the Gene Expression Omnibus database.The GSE123658 dataset analyzed whole blood RNA-seq data from type 1 diabetic patients and healthy volunteers. The GSE110914 dataset analyzed neutrophils purified from peripheral blood of patients with symptomatic and pre-symptomatic type 1 diabetes (T1D), at risk of T1D, and healthy controls. Immune cell infiltration analysis was performed to identify abnormally infiltrating immune cells. Differentially expressed immune genes (DEIGs) in T1D samples were identified, followed by the construction of an immune gene signature (IGS) using a protein-protein interaction (PPI) network and Least absolute shrinkage and selection operator Cox regression analyses (LASSO Cox regression analyses). The regulatory mechanisms underlying IGS were explored using gene set enrichment analysis. Furthermore, expression validation, diagnostic efficacy evaluation, and upstream miRNA prediction of hub signature genes were performed. We verified the miRNA expression of the key gene colony stimulating factor 1 (CSF1) and microRNA-326 (miR-326) by reverse transcription-quantitative PCR (RT‒qPCR). Results: The proportion of infiltrating T and natural killer (NK) cells differed between the T1D and control samples, and 207 immune genes (IGs) related to these immune cells were extracted. After differential expression, PPI, and LASSO Cox regression analyses, four signature DEIGs were identified for IGS construction: notch receptor 1 (NOTCH1), Janus kinase 3 (JAK3), tumor necrosis factor receptor superfamily member 4(TNFRSF4), and CSF1. Key pathways such as the Toll-like receptor signaling pathway were significantly activated in the high-risk group. Moreover, the upregulation of CSF1 in T1D samples was confirmed using a validation dataset, and CSF1 showed high diagnostic efficacy for T1D. Furthermore, CSF1 was targeted by miR-326.We used validated key genes in T1D patients, several of which were confirmed by RT‒qPCR. Conclusion: In conclusion, the identified key IGs may play an important role in T1D. CSF1 can be developed as a novel diagnostic biomarker for T1D.

Trefoil factor 1 (TFF1) reduces cerebral edema and gastric mucosal injury by regulating the EGFR/Src/FAK pathway in an intracerebral hemorrhage rat model.

The destruction of the blood-brain barrier and damage to the gastrointestinal mucosa after intracerebral hemorrhage (ICH) are important reasons for its high disability and mortality rates. However, the exact etiology is not yet clear. In addition, there are currently no effective treatments for improving cerebral edema and gastric mucosal damage after ICH. Trefoil factor 1 (TFF1) is a secretory protein that plays a crucial role in maintaining the integrity and barrier function of the gastric mucosa, and it has been reported to have a protective effect on brain damage induced by various causes. This study utilized a rat model of ICH induced by type IV collagenase was utilized, and intervened with recombinant TFF1 protein from an external institute to investigate the protective mechanisms of TFF1 against brain edema and gastric mucosal damage after ICH. The results demonstrated that TFF1 alleviated the neurological function and gastric mucosal damage in the rat model of ICH induced by type IV collagenase. TFF1 may ensure the integrity of the blood-brain and gastric mucosal barriers by regulating the EGFR (epidermal growth factor receptor)/Src (non-receptor tyrosine kinase)/FAK (focal adhesion kinase) pathway. Clearly, the disruption of the blood-brain barrier and the destruction of the gastric mucosal barrier are key pathological features of ICH, and TFF1 can improve the progression of blood-brain barrier and gastric mucosal barrier disruption in ICH by regulating the EGFR/Src/FAK pathway. Therefore, TFF1 may be a potential target for the treatment of ICH.

Technological Advances Are Associated With Better Clinical Outcomes of Percutaneous Coronary Intervention in Patients With Unprotected Left Main Disease.

BACKGROUND: Few large-scale studies have evaluated the effectiveness of percutaneous coronary intervention (PCI) technological advances in the treatment of patients with unprotected left main coronary artery disease (LM-CAD). We aim to identify independent factors that affect the prognosis of PCI in patients with unprotected LM-CAD and to assess the impact of PCI technological advances on long-term clinical outcomes. METHODS AND RESULTS: A total of 4512 consecutive patients who underwent unprotected LM-CAD PCI at Fuwai Hospital from 2004 to 2016 were enrolled. Multivariable Cox proportional hazards model was used to identify which techniques can independently affect the incidence of major adverse cardiac events (MACEs; a composite of cardiac death, myocardial infarction, or target vessel revascularization). The incidence of 3-year MACEs was 9.0% (406/4512). Four new PCI techniques were identified as the independent protective factors of MACEs, including second-generation drug-eluting stents (hazard ratio [HR], 0.61 [95% CI, 0.37-0.99]), postdilatation (HR, 0.75 [95% CI, 0.59-0.94]), final kissing balloon inflation (HR, 0.78 [95% CI, 0.62-0.99]), and using intravascular ultrasound (HR, 0.78 [95% CI, 0.63-0.97]). The relative hazard of 3-year MACEs was reduced by ≈50% with use of all 4 techniques compared with no technique use (HR, 0.53 [95% CI, 0.32-0.87]). CONCLUSIONS: PCI technological advances including postdilatation, second-generation drug-eluting stent, final kissing balloon inflation, and intravascular ultrasound guidance were associated with improved clinical outcomes in patients who underwent unprotected LM-CAD PCI.

Supramolecular chirality capture in solvent monomer-based co-assemblies via in situ photopolymerization.

Supramolecular assemblies with chirality inversion were developed using a co-assembly system comprising solvent monomers and a pyridine-cholesterol gelator. The polarity-dependent chiralities were captured in situ through photopolymerization, enabling the formation of multi-color circularly polarized luminescence films.

Proteomics of plasma-derived extracellular vesicles reveals S100A8 as a novel biomarker for Alzheimer's disease: A preliminary study.

Extracellular vesicles (EVs) act as mediators for intercellular transfer of Aß and tau proteins, promoting the propagation of these pathological misfolded proteins throughout the brain in Alzheimer's disease (AD). Levels of blood exosomal Aß42, total Tau (t-Tau) and phosphorylated Tau (p-Tau) had a high correlation with their concentrations in cerebrospinal fluid (CSF), demonstrating that exosomal biomarkers have equal contribution as those in CSF for the diagnosis of AD. We aimed to comprehensively characterize the proteome of plasma-derived EVs to identify differentially expressed proteins (DEPs) and pathways in AD. Tandem mass tag (TMT) labeled quantitative proteomics was applied to analyze plasma-derived EV proteins in 9 AD patients and 9 healthy controls. 335 proteins were quantified, and 12 DEPs were identified including seven upregulated proteins and five down-regulated proteins. Oligomerized Aß1-42 induced SH-SY5Y cell damage model was built to mimic the pathological changes of AD, and small interfering RNA (siRNA) against S100A8 was used to knock down S100A8 expression. Results displayed S100A8 was down regulated in plasma-derived EVs from AD patients, while enriched in EVs derived from Aß1-42-induced SH-SY5Y cells. Furthermore, Aß1-42-induced SH-SY5Y cells treated with S100A8 siRNA showed decreased Aß levels in cell lysate and EVs, especially in EVs. SIGNIFICANCE: The investigation aimed to comprehensively characterize the proteome of plasma-derived EVs to identify DEPs and potential biomarker of AD. S100A8 was found down regulated in plasma-derived EVs from AD patients using TMT labeled quantitative proteomics. The diagnostic value of S100A8 was also confirmed using receiver operating characteristic curve (ROC) analysis. Furthermore, Aß1-42-induced SH-SY5Y cells treated with S100A8 siRNA showed decreased Aß levels in cell lysate and EVs, especially in EVs. The preliminary findings suggest that suppression of S100A8 expression inhibits Aß aggregation both in cell lysate and EVs from Aß1-42-induced SH-SY5Y cells, and S100A8 more likely regulates Aß aggregation via EVs. Therefore, plasma-derived EV S100A8 might be a potential biomarker of AD. Manipulation of S100A8 expression may be a novel therapeutic strategy in the treatment of AD.

Aucubin suppresses TLR4/NF-κB signalling to shift macrophages toward M2 phenotype in glucocorticoid-associated osteonecrosis of the femoral head.

In this study, we investigated whether the ability of aucubin to mitigate the pathology of GONFH involves suppression of TLR4/NF-κB signalling and promotion of macrophage polarization to an M2 phenotype. In necrotic bone tissues from GONFH patients, we compared levels of pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages as well as levels of TLR4/NF-κB signalling. In a rat model of GONFH, we examined the effects of aucubin on these parameters. We further explored its mechanism of action in a cell culture model of M1 macrophages. Necrotic bone tissues from GONFH patients contained a significantly increased macrophage M1/M2 ratio, and higher levels of TLR4, MYD88 and NF-κB p65 than bone tissues from patients with hip osteoarthritis. Treating GONFH rats with aucubin mitigated bone necrosis and demineralization as well as destruction of trabecular bone and marrow in a dose-dependent manner, based on micro-computed tomography. These therapeutic effects were associated with a decrease in the overall number of macrophages, decrease in the proportion of M1 macrophages, increase in the proportion of M2 macrophages, and downregulation of TLR4, MYD88 and NF-κB p65. These effects in vivo were confirmed by treating cultures of M1 macrophage-like cells with aucubin. Aucubin mitigates bone pathology in GONFH by suppressing TLR4/NF-κB signalling to shift macrophages from a pro- to anti-inflammatory phenotype.

Scutellaria baicalensis Polysaccharide-Mediated Green Synthesis of Smaller Silver Nanoparticles with Enhanced Antimicrobial and Antibiofilm Activity.

Silver nanoparticles (AgNPs) have attracted widespread attention in multidrug-resistant bacterial infections. However, the application of AgNPs synthesized by conventional methods is restricted by its high costs, toxicity, and poor stability. Herein, a water-soluble polysaccharide (Scutellaria baicalensis polysaccharide, SBP) rich in reducing sugars was used as both the reductant and stabilizer to greenly synthesize spherical AgNPs@SBP with smaller particle sizes (11.18 ± 2.50 nm) and higher negative zeta potential (-23.05 ± 2.76 mV), which was favorable to enhance its antimicrobial activity and improve pH and thermal stability. Besides, SBP facilitated the adhesion and penetration of AgNPs@SBP to methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Escherichia coli (CREC), thus significantly enhancing its antibacterial activity (increased by 32-fold and 64-fold, respectively). Likewise, AgNPs@SBP at a low concentration (7.8 µg/mL) could effectively penetrate and inhibit nearly 90% of MRSA and CREC biofilm formation. Antimicrobial mechanism studies showed that AgNPs@SBP could lead to more severe cell membrane damage and genetic material leakage by upregulating reactive oxygen species and depolarizing mitochondrial membrane potential, ultimately resulting in the apoptosis of bacteria. Overall, the wrapping of SBP significantly enhanced the antibacterial and antibiofilm activity of AgNPs, which possessed great potential in the prevention and treatment of multidrug-resistant bacterial infections.