Soot nanoparticles promote ferroptosis in dopaminergic neurons via alteration of m6A RNA methylation in Parkinson's disease.

Soot nanoparticles (SNPs) are black carbon prevalent in atmospheric environment with significant impacts on public health, leading to neurodegenerative diseases including development of Parkinson's disease (PD). This study investigated the effects of SNPs exposure on PD symptoms, employing both in vivo and in vitro PD models. In the in vivo experiments, animal behavior assessments showed that SNPs exposure exacerbated motor and cognitive impairments in PD mice. Molecular biology techniques further unveiled that SNPs aggravated degeneration of dopaminergic neurons. In vitro experiments revealed that SNPs exposure intensified ferroptosis of PD cells by increasing reactive oxygen species and iron ion levels, while reducing glutathione levels and mitochondrial membrane potential. Sequencing tests indicated elevated N6-methyladenosine (m6A) alteration of the ferroptosis-related protein, acyl-CoA synthetase long chain family member 4 (ACSL4). This study demonstrates that SNPs may exacerbate the onset and progression of PD by recruiting YTH domain-containing family protein 1 (YTHDF1) protein, enhancing m6A methylation in the ACSL4 5'UTR, amplifying ACSL4 protein expression, and accelerating the ferroptosis process in dopaminergic neurons. These molecular mechanisms underlying SNPs exacerbation of PD development may provide crucial insights for formulating environmental safety regulations and potential therapeutic strategies addressing PD in populations residing in regions with varied air quality.

Inhibition and disaggregation effect of flavonoid-derived carbonized polymer dots on protein amyloid aggregation.

In this research, four water-insoluble flavonoid compounds were utilized and reacted with arginine to prepare four carbonized polymer dots with good water-solubility in a hydrothermal reactor. Structural characterization demonstrated that the prepared carbonized polymer dots were classic core-shell structure. Effect of the prepared carbonized polymer dots on protein amyloid aggregation was further investigated using hen egg white lysozyme and human lysozyme as model protein in aqueous solution. All of the prepared carbonized polymer dots could retard the amyloid aggregation of hen egg white lysozyme and human lysozyme in a dose-depended manner. All measurements displayed that the inhibition ratio of luteolin-derived carbonized polymer dots (CPDs-1) was higher than that of the other three carbonized polymer dots under the same dosage. This result may be interpreted by the highest content of phenolic hydroxyl groups on the periphery. The inhibition ratio of CPDs-1 on hen egg white lysozyme and human lysozyme reached 88 % and 83 % at the concentration of 0.5 mg/mL, respectively. CPDs-1 also could disaggregate the formed mature amyloid fibrils into short aggregates.

Dissimilar effects of the hydrophilic carbon dots on the amyloid aggregation of two model proteins and the mechanism discussion.

Many proteins could aggregate into amyloid fibrils under certain conditions. However, the aggregation process and morphology of the fibrils may be significantly different because of the distinct protein structure. In this article, the hydrophilic carbon dots (Lys-CA-CDs) were prepared using lysine (Lys) and citric acid (CA) as reactant under the assistance of a microwave. The dissimilar modulation effect of Lys-CA-CDs on the aggregation process of distinct structure protein was further investigated, where bovine serum albumin (BSA) and hen egg white lysozyme (HEWL) were chosen as model proteins. All results showed that Lys-CA-CDs displayed the contrary influence on the aggregation process of BSA and HEWL. Lys-CA-CDs could induce BSA to aggregate into more wormlike fibrils and inhibit the aggregation of HEWL into hair-like fibrils. The influence on the aggregation process of BSA may be assigned to the increased concentration of BSA around the Lys-CA-CDs caused by their interaction. However, inserting of Lys-CA-CDs into the inner structure of HEWL led to the change of protein secondary structure. The change of secondary structure further made it difficult for HEWL to aggregate into fibrils and Lys-CA-CDs showed the inhibition effect on HEWL aggregation.

Ablation-induced left atrial mechanical dysfunction recovers in weeks after ablation.

BACKGROUND: The immediate impact of catheter ablation on left atrial mechanical function and the timeline for its recovery in patients undergoing ablation for atrial fibrillation (AF) remain uncertain. The mechanical function response to catheter ablation in patients with different AF types is poorly understood. METHODS: A total of 113 AF patients were included in this retrospective study. Each patient had three magnetic resonance imaging (MRI) studies in sinus rhythm: one pre-ablation, one immediate post-ablation (within 2 days after ablation), and one post-ablation follow-up MRI (≤ 3 months). We used feature tracking in the MRI cine images to determine peak longitudinal atrial strain (PLAS). We evaluated the change in strain from pre-ablation, immediately after ablation to post-ablation follow-up in a short-term study (< 50 days) and a 3-month study (3 months after ablation). RESULTS: The PLAS exhibited a notable reduction immediately after ablation, compared to both pre-ablation levels and those observed in follow-up studies conducted at short-term (11.1 ± 9.0 days) and 3-month (69.6 ± 39.6 days) intervals. However, there was no difference between follow-up and pre-ablation PLAS. The PLAS returned to 95% pre-ablation level within 10 days. Paroxysmal AF patients had significantly higher pre-ablation PLAS than persistent AF patients in pre-ablation MRIs. Both type AF patients had significantly lower immediate post-ablation PLAS compared with pre-ablation and post-ablation PLAS. CONCLUSION: The present study suggested a significant drop in PLAS immediately after ablation. Left atrial mechanical function recovered within 10 days after ablation. The drop in PLAS did not show a substantial difference between paroxysmal and persistent AF patients.

Integration of Single-Cell and Bulk RNA-seq Data to Identify the Cancer-Associated Fibroblast Subtypes and Risk Model in Glioma.

Cancer-associated fibroblasts (CAFs) are an important component of the stroma. Studies showed that CAFs were pivotally in glioma progression which have long been considered a promising therapeutic target. Therefore, the identification of prognostic CAF markers might facilitate the development of novel diagnostic and therapeutic approaches. A total of 1333 glioma samples were obtained from the TCGA and CGGA datasets. The EPIC, MCP-counter, and xCell algorithms were used to evaluate the relative proportion of CAFs in glioma. CAF markers were identified by the single-cell RNA-seq datasets (GSE141383) from the Tumor Immune Single-Cell Hub database. Unsupervised consensus clustering was used to divide the glioma patients into different distinct subgroups. The least absolute shrinkage and selection operator regression model was utilized to establish a CAF-related signature (CRS). Finally, the prognostic CAF markers were further validated in clinical specimens by RT‒qPCR. Combined single-cell RNA-seq analysis and differential expression analysis of samples with high and low proportions of CAFs revealed 23 prognostic CAF markers. By using unsupervised consensus clustering, glioma patients were divided into two distinct subtypes. Subsequently, based on 18 differentially expressed prognostic CAF markers between the two CAF subtypes, we developed and validated a new CRS model (including PCOLCE, TIMP1, and CLIC1). The nomogram and calibration curves indicated that the CRS was an accurate prognostic marker for glioma. In addition, patients in the high-CRS score group had higher immune infiltration and tumor mutation burden levels. Moreover, the CRS score had the potential to predict the response to immune checkpoint blockade (ICB) therapy and chemotherapy. Finally, the expression profiles of three CAF markers were verified by RT‒qPCR. In general, our study classified glioma patients into distinct subgroups based on CAF markers, which will facilitate the development of individualized therapy. We also provided insights into the role of the CRS in predicting the response to ICB and chemotherapy in glioma patients.

Projection-Angle-Sensor-Assisted X-ray Computed Tomography for Cylindrical Lithium-Ion Batteries.

X-ray computed tomography (XCT) has become a powerful technique for studying lithium-ion batteries, allowing non-destructive 3D imaging across multiple spatial scales. Image quality is particularly important for observing the internal structure of lithium-ion batteries. During multiple rotations, the existence of cumulative errors and random errors in the rotary table leads to errors in the projection angle, affecting the imaging quality of XCT. The accuracy of the projection angle is an important factor that directly affects imaging. However, the impact of the projection angle on XCT reconstruction imaging is difficult to quantify. Therefore, the required precision of the projection angle sensor cannot be determined explicitly. In this research, we selected a common 18650 cylindrical lithium-ion battery for experiments. By setting up an XCT scanning platform and installing an angle sensor to calibrate the projection angle, we proceeded with image reconstruction after introducing various angle errors. When comparing the results, we found that projection angle errors lead to the appearance of noise and many stripe artifacts in the image. This is particularly noticeable in the form of many irregular artifacts in the image background. The overall variation and residual projection error in detection indicators can effectively reflect the trend in image quality. This research analyzed the impact of projection angle errors on imaging and improved the quality of XCT imaging by installing angle sensors on a rotary table.

Isolation and Identification of Acer truncatum Endophytic Fungus Talaromyces verruculosus and Evaluation of Its Effects on Insoluble Phosphorus Absorption Capacity and Growth of Cucumber Seedlings.

The symbiosis between endophytic fungi and plants can promote the absorption of potassium, nitrogen, phosphorus, and other nutrients by plants. Phosphorus is one of the indispensable nutrient elements for plant growth and development. However, the content of available phosphorus in soil is very low, which limits the growth of plants. Phosphorus-soluble microorganisms can improve the utilization rate of insoluble phosphorus. In this study, Talaromyces verruculosus (T. verruculosus), a potential phosphorus-soluble fungus, was isolated from Acer truncatum, a plant with strong stress resistance, and its phosphorus-soluble ability in relation to cucumber seedlings under different treatment conditions was determined. In addition, the morphological, physiological, and biochemical indexes of the cucumber seedlings were assessed. The results show that T. verruculosus could solubilize tricalcium phosphate (TCP) and lecithin, and the solubilization effect of lecithin was higher than that of TCP. After the application of T. verruclosus, the leaf photosynthetic index increased significantly. The photosynthetic system damage caused by low phosphorus stress was alleviated, and the root morphological indexes of cucumber seedlings were increased. The plant height, stem diameter, and leaf area of cucumber seedlings treated with T. verruculosus were also significantly higher than those without treatment. Therefore, it was shown that T. verruculosus is a beneficial endophytic fungus that can promote plant growth and improve plant stress resistance. This study will provide a useful reference for further research on endophytic fungi to promote growth and improve plant stress resistance.

Understanding phosphorus fractions and influential factors on urban road deposited sediments.

Phosphorus (P) is a primary pollutant that builds-up on urban road surfaces. Understanding the fraction and load characteristics of P, as well as their relationship with urban factors, is helpful for assessing the ecological risk of urban receiving water bodies. This study presents the characteristics of build-up loads of P fractions in road-deposited sediments (RDS) in Guangzhou, China, analyzes their correlation with three urban factors (road, traffic, and land-use area), and then estimates the exceedance probability of P in stormwater runoff over the past 10 years. The results showed that detrital apatite phosphorus (De-P) performed the highest build-up load on urban road surfaces, followed by apatite phosphorus (Ca-P), iron-bound phosphorus (Fe-P), exchangeable phosphorus (Ex-P), aluminum-bound phosphorus (Al-P), organophosphorus (POP), dissolved inorganic phosphorus (DIP), occluded phosphorus (Oc-P), and dissolved organic phosphorus (DOP). Depression depth, road materials, and land-use fractions affected the P fractions. The P in the RDS may have originated from three distinct sources: road background, domestic waste, and untreated wastewater discharge. In the most recent 10 years, the event mean concentrations of total P in the RDS have had a 30 % probability of exceeding 0.4 mg L-1, which indicates a serious threat of P to receiving water bodies. The outcomes of this study are expected to provide valuable guidance for elucidating the principal categories of urban non-point source P pollution and enhancing the ecological health of urban water environments.

Neutrophil extracellular traps mediated by platelet microvesicles promote thrombosis and brain injury in acute ischemic stroke.

AIMS: Neutrophil extracellular traps (NETs) have been implicated in thrombotic diseases. There is no definitive explanation for how NETs form during acute ischemic strokes (AIS). The purpose of our study was to investigate the potential mechanism and role of NETs formation in the AIS process. METHODS: As well as 45 healthy subjects, 45 patients with AIS had ELISA tests performed to detect NET markers. Expression of high-mobility group box 1 (HMGB1) on platelet microvesicles (PMVs) was analyzed by flow cytometry in healthy subjects and AIS patients' blood samples. We established middle cerebral artery occlusion (MCAO) mice model to elucidate the interaction between PMPs and NETs. RESULTS: A significant elevation in NET markers was found in patient plasma in AIS patients, and neutrophils generated more NETs from patients' neutrophils. HMGB1 expression was upregulated on PMVs from AIS patients and induced NET formation. NETs enhanced Procoagulant activity (PCA) through tissue factor and via platelet activation. Targeting lactadherin in genetical and in pharmacology could regulate the formation of NETs in MCAO model. CONCLUSIONS: NETs mediated by PMVs derived HMGB1 exacerbate thrombosis and brain injury in AIS. Video Abstract.

Abscisic Acid Affects Phenolic Acid Content to Increase Tolerance to UV-B Stress in Rhododendron chrysanthum Pall.

The presence of the ozone hole increases the amount of UV radiation reaching a plant's surface, and UV-B radiation is an abiotic stress capable of affecting plant growth. Rhododendron chrysanthum Pall. (R. chrysanthum) grows in alpine regions, where strong UV-B radiation is present, and has been able to adapt to strong UV-B radiation over a long period of evolution. We investigated the response of R. chrysanthum leaves to UV-B radiation using widely targeted metabolomics and transcriptomics. Although phytohormones have been studied for many years in plant growth and development and adaptation to environmental stresses, this paper is innovative in terms of the species studied and the methods used. Using unique species and the latest research methods, this paper was able to add information to this topic for the species R. chrysanthum. We treated R. chrysanthum grown in a simulated alpine environment, with group M receiving no UV-B radiation and groups N and Q (externally applied abscisic acid treatment) receiving UV-B radiation for 2 days (8 h per day). The results of the MN group showed significant changes in phenolic acid accumulation and differential expression of genes related to phenolic acid synthesis in leaves of R. chrysanthum after UV-B radiation. We combined transcriptomics and metabolomics data to map the metabolic regulatory network of phenolic acids under UV-B stress in order to investigate the response of such secondary metabolites to stress. L-phenylalanine, L-tyrosine and phenylpyruvic acid contents in R. chrysanthum were significantly increased after UV-B radiation. Simultaneously, the levels of 3-hydroxyphenylacetic acid, 2-phenylethanol, anthranilate, 2-hydroxycinnamic acid, 3-hydroxycinnamic acid, α-hydroxycinnamic acid and 2-hydroxy-3-phenylpropanoic acid in this pathway were elevated in response to UV-B stress. In contrast, the study in the NQ group found that externally applied abscisic acid (ABA) in R. chrysanthum had greater tolerance to UV-B radiation, and phenolic acid accumulation under the influence of ABA also showed greater differences. The contents of 2-phenylethanol, 1-o-p-coumaroyl-ß-d-glucose, 2-hydroxy-3-phenylpropanoic acid, 3-(4-hydroxyphenyl)-propionic acid and 3-o-feruloylquinic ac-id-o-glucoside were significantly elevated in R. chrysanthum after external application of ABA to protect against UV-B stress. Taken together, these studies of the three groups indicated that ABA can influence phenolic acid production to promote the response of R. chrysanthum to UV-B stress, which provided a theoretical reference for the study of its complex molecular regulatory mechanism.

The role of angiotensin II activation of yes-associated protein/PDZ-binding motif signaling in hypertensive cardiac and vascular remodeling.

Vascular remodeling is the pathogenic basis of hypertension and end organ injury, and the proliferation of vascular smooth muscle cells (VSMCs) is central to vascular remodeling. Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are key effectors of the Hippo pathway and crucial for controlling cell proliferation, apoptosis and differentiation. The present study investigated the role of YAP/TAZ in cardiac and vascular remodeling of angiotensin II-induced hypertension. Ang II induced YAP/TAZ activation in the heart and aorta, which was prevented by YAP/TAZ inhibitor verteporfin. Treatment with verteporfin significantly reduced Ang II-induced cardiac and vascular hypertrophy with a mild reduction in systolic blood pressure (SBP), verteporfin attenuated Ang II-induced cardiac and aortic fibrosis with the inhibition of transform growth factor (TGF)ß/Smad2/3 fibrotic signaling and extracellular matrix collagen I deposition. Ang II induced Rho A, extracellular signal-regulated kinase 1/2 (ERK1/2) and YAP/TAZ activation in VSMCs, either Rho kinase inhibitor fasudil or ERK inhibitor PD98059 suppressed Ang II-induced YAP/TAZ activation, cell proliferation and fibrosis of VSMCs. Verteporfin also inhibited Ang II-induced VSMC proliferation and fibrotic TGFß1/Smad2/3 pathway. These results demonstrate that Ang II activates YAP/TAZ via Rho kinase/ERK1/2 pathway in VSMCs, which may contribute to cardiac and vascular remodeling in hypertension. Our results suggest that YAP/TAZ plays a critical role in the pathogenesis of hypertension and end organ damage, and targeting the YAP/TAZ pathway may be a new strategy for the prevention and treatment of hypertension and cardiovascular diseases.

The evolution of indium precipitation in gallium focused ion beam prepared samples of InGaAs/InAlAs quantum wells under electron beam irradiation.

Gallium ion (Ga+ ) beam damage induced indium (In) precipitation in indium gallium arsenide (InGaAs)/indium aluminium arsenide (InAlAs) multiple quantum wells and its corresponding evolution under electron beam irradiation was investigated by valence electron energy loss spectroscopy (VEELS) and high-angle annular dark-field imaging (HAADF) in scanning transmission electron microscopy (STEM). Compared with argon ion milling for sample preparation, the heavier projectiles of Ga+ ions pose a risk to trigger In formation in the form of tiny metallic In clusters. These are shown to be sensitive to electron irradiation and can increase in number and size under the electron beam, deteriorating the structure. Our finding reveals the potential risk of formation of In clusters during focused ion beam (FIB) preparation of InGaAs/InAlAs quantum well samples and their subsequent growth under STEM-HAADF imaging, where initially invisible In clusters of a few atoms can move and swell during electron beam exposure.

Rhododendron chrysanthum's Primary Metabolites Are Converted to Phenolics More Quickly When Exposed to UV-B Radiation.

The plant defense system is immediately triggered by UV-B irradiation, particularly the production of metabolites and enzymes involved in the UV-B response. Although substantial research on UV-B-related molecular responses in Arabidopsis has been conducted, comparatively few studies have examined the precise consequences of direct UV-B treatment on R. chrysanthum. The ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) methodology and TMT quantitative proteomics are used in this study to describe the metabolic response of R. chrysanthum to UV-B radiation and annotate the response mechanism of the primary metabolism and phenolic metabolism of R. chrysanthum. The outcomes demonstrated that following UV-B radiation, the primary metabolites (L-phenylalanine and D-lactose*) underwent considerable changes to varying degrees. This gives a solid theoretical foundation for investigating the use of precursor substances, such as phenylalanine, to aid plants in overcoming abiotic stressors. The external application of ABA produced a considerable increase in the phenolic content and improved the plants' resistance to UV-B damage. Our hypothesis is that externally applied ABA may work in concert with UV-B to facilitate the transformation of primary metabolites into phenolic compounds. This hypothesis offers a framework for investigating how ABA can increase a plant's phenolic content in order to help the plant withstand abiotic stressors. Overall, this study revealed alterations and mechanisms of primary and secondary metabolic strategies in response to UV-B radiation.

Using mixed reality technique combines multimodal imaging signatures to adjuvant glioma photodynamic therapy.

Background: Photodynamic therapy (PDT) promotes significant tumor regression and extends the lifetime of patients. The actual operation of PDT often relies on the subjective judgment of experienced neurosurgeons. Patients can benefit more from precisely targeting PDT's key operating zones. Methods: We used magnetic resonance imaging scans and created 3D digital models of patient anatomy. Multiple images are aligned and merged in STL format. Neurosurgeons use HoloLens to import reconstructions and assist in PDT execution. Also, immunohistochemistry was used to explore the association of hyperperfusion sites in PDT of glioma with patient survival. Results: We constructed satisfactory 3D visualization of glioma models and accurately localized the hyperperfused areas of the tumor. Tumor tissue taken in these areas was rich in CD31, VEGFA and EGFR that were associated with poor prognosis in glioma patients. We report the first study using MR technology combined with PDT in the treatment of glioma. Based on this model, neurosurgeons can focus PDT on the hyperperfused area of the glioma. A direct benefit was expected for the patients in this treatment. Conclusion: Using the Mixed Reality technique combines multimodal imaging signatures to adjuvant glioma PDT can better exploit the vascular sealing effect of PDT on glioma.

Expression of intra-tumoral necrosis-associated cytokine pattern correlated with prognosis and immune status in glioma.

Intra-tumoral necrosis (ITN) is reported to be an independent prognostic factor in glioma. However, knowledge of ITN is mainly limited to pseudopalisadwe, while its other aspects were neglected. Therefore, a deeper understanding of ITN could be valuable for understanding its exact role in glioma. The only reliable ITN model was time-dependently achieved with the GL261 syngeneic mouse model. The ITN-associated expression pattern was enriched from RNA sequencing. TCGA glioma samples were clustered into a high-expression group (HEG) and a low-expression group (LEG) based on their pattern and their association with prognosis, clinical status, immune status, and therapeutic responsiveness were compared. Mouse glioma with ITN demonstrated invasive histology. Cytokine signaling was significantly enriched in necrotic mouse glioma compared with non-necrotic glioma tissues. Nine pro-inflammatory (IL6, PPBP, IL1A, TNFSF11, CXCL11, CXCL9, CXCL10, CXCL3, and CCL8) and two anti-inflammatory cytokine (IL1RN and IL10) genes were found to be related to ITN-associated cytokine patterns. Comparative analysis showed that HEG had a significantly shorter survival time, five differentially distributed clinical statuses, more infiltrated immune cells, greater expression of immune checkpoints, and better therapeutic responsiveness than LEG. In conclusion, the ITN-associated cytokine pattern is characteristically expressed in glioma with ITN and might indicate necrosis missed in histology diagnosis. Its expression pattern could predict the prognosis, tumor grade, immune status, and therapeutic responsiveness of glioma patients.

Large-scale surface hopping simulation of charge transport in hexagonal molecular crystals: role of electronic coupling signs.

In large-scale surface hopping simulations with a huge number of electronic states, trivial crossings could easily lead to incorrect long-range charge transfer and induce large numerical errors. We here study the charge transport in two-dimensional hexagonal molecular crystals with a parameter-free full crossing corrected global flux surface hopping method. Fast time-step size convergence and system size independence have been realized in large systems containing thousands of molecular sites. In hexagonal systems, each molecular site has six nearest neighbours. We find that the signs of their electronic couplings have a strong impact on the charge mobility and delocalization strength. In particular, changing the signs of electronic couplings can even lead to a transition from hopping to band-like transport. In comparison, such phenomena cannot be observed in extensively studied two-dimensional square systems. This is attributed to symmetry of the electronic Hamiltonian and distribution of the energy levels. Due to its high performance, the proposed approach is promising to be applied to more realistic and complex systems for molecular design.

Neutrophil extracellular traps contribute to coagulopathy after traumatic brain injury.

Coagulopathy contributes to the majority of deaths and disabilities associated with traumatic brain injury (TBI). Whether neutrophil extracellular traps (NETs) contribute to an abnormal coagulation state in the acute phase of TBI remains unknown. Our objectives were to demonstrate the definitive role of NETs in coagulopathy in TBI. We detected NET markers in 128 TBI patients and 34 healthy individuals. Neutrophil-platelet aggregates were detected in blood samples from TBI patients and healthy individuals using flow cytometry and staining for CD41 and CD66b. Endothelial cells were incubated with isolated NETs and we detected the expression of vascular endothelial cadherin, syndecan-1, thrombomodulin, von Willebrand factor, phosphatidylserine, and tissue factor. In addition, we established a TBI mouse model to determine the potential role of NETs in TBI-associated coagulopathy. NET generation was mediated by high mobility group box 1 (HMGB1) from activated platelets and contributed to procoagulant activity in TBI. Furthermore, coculture experiments indicated that NETs damaged the endothelial barrier and caused these cells to assume a procoagulant phenotype. Moreover, the administration of DNase I before or after brain trauma markedly reduced coagulopathy and improved the survival and clinical outcome of mice with TBI.

Rapid progression of subcutaneous glioblastoma: A case report and literature review.

Extra-neural spread of glioblastoma (GBM) is extremely rare. We report a case of postoperative intracranial GBM spreading to the subcutaneous tissue via the channel of craniotomy defect in a 73-year-old woman. Radiological images and histopathology indicate that the tumor microenvironment of the subcutaneous tumor is clearly different from the intracranial tumor. We also model the invasion of GBM cells through the dura-skull defect in mouse. The retrospective analysis of GBM with scalp metastases suggests that craniectomy is a direct cause of subcutaneous metastasis in patients with GBM. Imaging examinations of other sites for systemic screening is also recommended to look for metastases outside the brain when GBM invades the scalp or metastasizes to it.

Effect of mono- and diketone group in curcumin analogues on amyloid fibrillation of hen egg white lysozyme.

Curcumin has attracted more attention because of its inhibition efficacy on protein amyloid fibrillation. However, the inhibition mechanism was still ambiguous and the clinical application of curcumin was greatly limited because of its poor stability at physiological conditions for the presence of ß-diketone moiety. In this paper, a new mono-ketone-containing curcumin analogue (MDHC) was designed and synthesized to realize the possible inhibition mechanism and unveil the important role of ß-diketone moiety of curcumin in the inhibition process of amyloid fibrillation using hen egg white lysozyme (HEWL) as model protein. Although all experiment results (ThT, CR, ANS and TEM) showed that the inhibitory capacity of curcumin was better than MDHC, MDHC still could show obvious inhibition effect. Molecular docking showed that both curcumin and MDHC could bind with HEWL by hydrogen bond of phenloic hydroxyl and the binding energy of MDHC was higher than that of curcumin. All the findings inferred that ß-diketone group was one of great important groups in the inhibition process of HEWL amyloid fibrillation, which provided more room to construct novel inhibition reagents.

The efficacy and safety of radial endobronchial ultrasound-guided transbronchial lung cryobiopsy in the diagnosis of lung disease.

Background: Transbronchial lung cryobiopsy (TBLC) is a novel technology in which a cryoprobe is used to obtain large tissue samples from the lungs of patients with interstitial lung diseases (ILDs) and peripheral pulmonary lesions (PPLs). We aimed to determine the efficacy and safety of TBLC in the diagnosis of peripheral lung diseases in the Endoscopy Center of Shanghai Pulmonary Hospital. Further, the application value of radial endobronchial ultrasound (R-EBUS) used to determine the optimal area for cryobiopsy was evaluated in this study. Methods: In this retrospective study, the data of patients with unclarified ILDs or PPLs who underwent TBLC guided by R-EBUS between April 2020 and December 2021 at Shanghai Pulmonary Hospital in China were analyzed. Results: A total of 137 patients [72 men, 65 women; median age, 52 years (range, 24-76 years)] were enrolled in the study. Out of the 137 patients included in the study, 123 (89.8%) were diagnosed after multidisciplinary discussions (MDDs), including 105 (85.4%) with ILD, 10 (8.1%) with tuberculosis, and 8 (6.5%) with a malignant tumor. Sixty-five (47.4%) patients had a definitive pathologic diagnosis through TBLC, including 54 (83.1%) with ILD, 5 (7.7%) with tuberculosis and 6 (9.2%) with malignant tumors. The overall pathological diagnosis rate was 47.4%. In addition to clarifying the blood supply situation of the candidate target, R-EBUS detected lesions in 44 (32.1%) patients. Mild and moderate bleeding occurred in 75.2% and 24.8% of patients, respectively. No cases of severe bleeding were observed. Pneumothorax occurred in 6 (4.4%) patients, of which 2 recovered without additional treatment, and 4 (66.7%) needed closed thoracic drainage. Hydropneumothorax and mediastinal emphysema occurred in one patient each. No patients died due to TBLC. Conclusions: R-EBUS-guided TBLC is safe and effective for the diagnosis of lung diseases, including ILDs and other PPLs. R-EBUS can guide cryobiopsy and avoid the potential risk of severe bleeding as well as radiation exposure. The pathological diagnosis rate of ILDs is relatively low, and MDD plays an important role in the diagnosis of ILDs.