Network pharmacology analysis of the active ingredients of Corydalis hendersonii Hemsl. and their effects on eliminating neuroinflammation and improving motor functions in MPTP-intoxicated mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Corydalis hendersonii Hemsl. (CH), is a traditional Tibetan medicine used in highland areas for the treatment of alpine polycythemia, ulcers and various inflammatory diseases. Its antioxidant and anti-inflammatory effects have been demonstrated in experimental mice. Loss of dopaminergic neurons due to oxidative damage is thought to be an important factor in the development of PD, the potential antioxidant, anti-inflammatory effects of CH could potentially be used for PD treatment. AIM OF THE STUDY: To identify potential targets of CH using network pharmacology and to investigate the neuroprotective effects in cultured cell models and in MPTP-intoxicated mice. MATERIALS AND METHODS: The main chemical components of CH were analyzed by UPLC-MS/MS and their potential targets of action or signaling pathways were analyzed using network pharmacology. MPP + or LPS was added to SH-SY5Y or BV2 cells, respectively, to establish cellular models. MPTP was administered to C57BL/6J mice to induce inflammation and dopaminergic neuron loss as well as dyskinesia, followed by behavioral analysis to determine the role of CH in eliminating inflammation, avoiding neuron loss, and improving dyskinesia. RESULTS: CH contains 241 alkaloids, 213 flavonoids, 177 terpenoids and 114 phenolic compounds. The targets crossover between CH and PD yielded 210 potential therapeutic targets, especially growth factors and inflammatory pathway-related genes, such as BDNF, NF-κB, as potential key targets. In cultured cells, CHE eliminated MPP + -induced impairment of cell viability as well as LPS-induced inflammation, respectively. In mice, CHE ameliorated MPTP-induced dyskinesia and rescued the loss of dopaminergic neurons in the substantia nigra and striatum. Mechanistically, CHE effectively maintained the activity of the BDNF-TrkB/Akt signaling pathway, accordingly, inhibited inflammatory signaling pathways such as HIF-1α/PKM2 and Notch/NF-kB. CONCLUSIONS: CH performed well in eliminating inflammation and improving locomotor deficits in mice, and its potent active ingredients are worthy of subsequent research and development.

Determination of glycidyl fatty acid esters in edible vegetable oils by HPLC-ESI-QQQ-MS/MS combined with cryo-degreasing tandem dispersive solid-phase extraction.

Glycidyl fatty acid esters (GEs) have been identified as food contaminants that can form during the processing and heating of edible oils. Their widespread occurrence raises potential concerns for consumers. This study aimed to develop a simple and effective analytical method for molecular recognition using mass spectrometry fragmentation patterns. Furthermore, it sought to simultaneously and quantitatively determine five common GEs in highly complex fatty matrices (oils) using high-performance liquid chromatography-triple quadrupole tandem mass spectrometry (HPLC-ESI-QQQ-MS/MS). An extraction method using acetonitrile was used, and the purification of the extract was optimized using cryo-degreasing-tandem dispersive solid-phase extraction (d-SPE) to eliminate fatty interferents. The method validation yielded recoveries ranging from 81.17% to 109.28% and the method precision was < 10.00%. The limits of quantification ranged from 0.08 to 0.21 ng/g, which is below the current legal limits. This approach may play a crucial role in ensuring food safety.

Insight into differences in whey proteome from human and eight dairy animal species for formula humanization.

Human breastmilk fulfills the nutritional needs of infants and therefore is the best template for formula. In this study, whey proteins were investigated among human and eight dairy animal species using label-free proteomics approach. Totally, 965 proteins from milk whey were identified and large variations were observed between human and animals. Several proteins, including ß-galactosidase, fatty acid synthase, osteopontin, lactoferrin, mannose receptor, and complement C4-A, which are associated with digestion and immune response, exhibited significantly higher levels in human milk whey. Conversely, specific animal milk whey demonstrated elevated abundance of lipocalin 2, lysozyme, and glycosylation-dependent cell adhesion molecule 1. These differential proteins are enriched in complement and coagulation cascades, lysosome, and phagosome pathways. The findings shed light on the variations in the whey proteome composition between human and animal milk, which can contribute to optimizing formula humanization.

An unusual case of acquired angioedema associated with monoclonal gammopathies of uncertain significance

Acquired angioedema (AAE) is a rare disease due to the C1 esterase inhibitor (C1-INH) deficiency. Clinically, its symptoms are similar to hereditary angioedema (HAE) with hereditary C1-INH deficiency. Both conditions have the potential to cause upper airway obstruction, which can be fatal in clinical practice and thus require intense attention. Here, we’d like to discuss the clinical presentation, diagnosis and follow up of a special case of AAE associated with monoclonal gammopathies of unknown significance (MGUS) with recurrent upper airway obstruction. The patient was regularly followed up after being discharged from our ward. Measurements of C3–C4 levels were carried out by a hematological test. Due to the rarity of such a disease, especially in Chinese people, relevant diagnosis methods are missing in this patient, so the patient was only diagnosed with AAE-C1-INH associated with MGUS clinically. The latest follow up showed that he still underwent recurrent upper airway obstruction; thus, he remained in a tracheostomy state due to a lack of proper medication prophylaxis and died eventually. This unusual case reminds emergency physicians to pay attention to such disease during clinical practice, and relevant diagnosis method should be improved (AU)

SnSe Nanosheet Array on Carbon Cloth as a High-Capacity Anode for Sodium-Ion Batteries.

Binder-free electrodes offer a great opportunity for developing high-performance sodium-ion batteries (SIBs) aiming at the application in energy storage devices. Tin selenide (SnSe) is considered to be a promising anode material for SIBs owing to its high theoretical capacity (780 mA h g-1). In this work, a SnSe nanosheet array (SnSe NS) on a carbon cloth is prepared using a vacuum thermal evaporation method. The as-prepared SnSe NS electrode does not have metal current collectors, binders, or any conductive additives. In comparison with the electrode of SnSe blocky particles (SnSe BP), the SnSe NS electrode delivers a higher initial charge capacity of 713 mA h g-1 at a current density of 0.1C and maintains a higher charge capacity of 410 mA h g-1 after 50 cycles. Furthermore, the electrochemical behaviors of the SnSe NS electrode are determined via pseudocapacitance and electrochemical impedance spectroscopy measurements, indicating a faster kinetic process of the SnSe NS electrode compared to that of the SnSe BP. Operando X-ray diffraction measurements prove that the SnSe NS exhibits better phase reversibility than the SnSe BP. After the cycles, the SnSe NS electrode still maintains its particular structure. This work provides a feasible method to prepare SnSe nanostructures with high capacity and improved sodium ion diffusion ability.

Effect of bladder filling status on positioning errors in post-hysterectomy cervical cancer radiotherapy.

Objective: To investigate the effect of different bladder filling states on positioning errors in radiotherapy for cervical cancer and obtain the reference range of bladder filling consistency during radiotherapy.Methods: Patients who underwent postoperative radiotherapy for cervical cancer in Nantong Tumor Hospital from October 2018 to December 2019 were selected. According to the bladder filling deviation, they were divided into group A1 (deviation < 20%) and group B1 (deviation ≥ 20%). The bladder filling variations of the two groups were compared with different positioning errors. Group A2 has a positioning error of <0.4 cm, and group B2 has a positioning error of ≥0.4 cm. The reference range of bladder filling consistency during radiotherapy is obtained by analyzing the composition ratio of different positioning errors of bladder filling deviation.Results: This study included 195 patients with cervical cancer. The error of longitudinal and vertical position in group B1 was significantly higher than that in group A1 (0.50 ± 0.34 vs. 0.26 ± 0.22 cm, p < 0.001, and 0.22 ± 0.17 vs. 0.16 ± 0.12 cm, p < 0.001). Compared with group B2, the absolute deviation of bladder filling in group A2 (54.1% ± 54.4% vs. 25.6% ± 22.7%, p < 0.001) was slight. The chi-square test showed significant differences in the proportion of the positioning state of different bladder filling forms (χ2 = 31.006, p < 0.001). In addition, there was a significant difference in the proportion of stability errors in patients with poor stability in different directions (χ2 = 118.551, p < 0.001).Conclusion: In patients with cervical cancer fixed in the supine position, a bladder capacity deviation <20% is easier to achieve excellent positioning with, and it can better control the positioning error of radiotherapy and ensure the positioning accuracy of dose distribution to the target area. It can also achieve good tumor treatment effects. This range can be used as a reference for bladder filling consistency in patients with cervical cancer undergoing radiotherapy.

Performance evaluation for medical alliance in China based on a novel multi-attribute group decision-making technique with Archimedean copulas-based Hamy operators and extended best-worst method.

Background: Medical alliance plays an important role in promoting resource sharing, optimizing the allocation of medical resources, establishing a hierarchical diagnosis and treatment system featuring primary diagnosis at the grassroots level, a two-way referral system, separated treatment for acute and chronic diseases, and dynamic cooperation. Thus, comprehensive performance evaluation for medical alliance is a necessary research that involves a multi-attribute group decision-making problem. Objective: The aim of this paper is to develop a new multi-attribute group decision-making evaluation framework and new weight method to better efficaciously resolve the issues of evaluation for the medical alliance. Methods: Firstly, Archimedean copula and co-copula operational rules, called Archimedean co-copula, and the form of q-rung orthopair fuzzy Hamy mean aggregation operator based on Archimedean co-copula operational rules are also developed. Secondly, an extended q-rung orthopair fuzzy extended best-worst method satisfying multiplicative consistency is developed to originate the weight information of the attributes. The new weight method can integrate the membership and non-membership of assessment information, improve constancy for group decision making and get an extremely reliable weight consequence. Finally, a novel multi-attribute group decision-making framework is presented based on the proposed q-rung orthopair fuzzy Archimedean copula and co-copula Hamy mean aggregation operator and q-rung orthopair fuzzy Euclidean best-worst method. Furthermore, the new multi-attribute group decision-making method is applied to comprehensive performance evaluation for medical alliance in Shanghai, and the effectiveness of the new method is also demonstrated. Results: The results show that the proposed multi-attribute group decision-making method with Archimedean copulas-based Hamy operators and extended best-worst in this paper outperforms some existing methods and provides support for policymakers seeking the use of patient- and community-centered health evaluations to improve health services. Conclusion: The proposed method is a theoretical guidance method and a good reference for the evaluation of medical alliances of other regions in China.

An unusual case of acquired angioedema associated with monoclonal gammopathies of uncertain significance.

Acquired angioedema (AAE) is a rare disease due to the C1 esterase inhibitor (C1-INH) deficiency. Clinically, its symptoms are similar to hereditary angioedema (HAE) with hereditary C1-INH deficiency. Both conditions have the potential to cause upper airway obstruction, which can be fatal in clinical practice and thus require intense attention. Here, we'd like to discuss the clinical presentation, diagnosis and follow up of a special case of AAE associated with monoclonal gammopathies of unknown significance (MGUS) with recurrent upper airway obstruction. The patient was regularly followed up after being discharged from our ward. Measurements of C3-C4 levels were carried out by a hematological test. Due to the rarity of such a disease, especially in Chinese people, relevant diagnosis methods are missing in this patient, so the patient was only diagnosed with AAE-C1-INH associated with MGUS clinically. The latest follow up showed that he still underwent recurrent upper airway obstruction; thus, he remained in a tracheostomy state due to a lack of proper medication prophylaxis and died eventually. This unusual case reminds emergency physicians to pay attention to such disease during clinical practice, and relevant diagnosis method should be improved.

CD8+ T cell infiltration and proliferation in the brainstem during experimental cerebral malaria.

INTRODUCTION: Cerebral malaria (CM) is a lethal neuroinflammatory disease caused by Plasmodium infection. Immune cells and brain parenchyma cells contribute to the pathogenesis of CM. However, a systematic examination of the changes that occur in the brain parenchyma region during CM at the single-cell resolution is still poorly studied. AIMS: To explore cell composition and CD8+ T cell infiltration, single-cell RNA sequencing (scRNA-seq) was performed on the brainstems of healthy and experimental cerebral malaria (ECM) mice. Then CD8+ T cell infiltration was confirmed by flow cytometry and immunofluorescence assays. Subsequently, the characteristics of the brain-infiltrated CD8+ T cells were analyzed. Finally, the interactions between parenchyma cells and brain-infiltrated CD8+ T cells were studied with an astrocytes-CD8+ T cell cocultured model. RESULTS: The brainstem is the most severely damaged site during ECM. ScRNA-seq revealed a large number of CD8+ T cells infiltrating into the brainstem in ECM mice. Brain-infiltrated CD8+ T cells were highly activated according to scRNA-seq, immunofluorescence, and flow cytometry assays. Further analysis found a subset of ki-67+ CD8+ T cells that have a higher transcriptional level of genes related to T cell function, activation, and proliferation, suggesting that they were exposed to specific antigens presented by brain parenchyma cells. Brain-infiltrated CD8+ T cells were the only prominent source of IFN-γ in this single-cell analysis. Astrocytes, which have a high interferon response, act as cross-presenting cells to recruit and re-activate brain-infiltrated CD8+ T cells. We also found that brain-infiltrated CD8+ T cells were highly expressed immune checkpoint molecule PD-1, while parenchyma cells showed up-regulation of PD-L1 after infection. CONCLUSIONS: These findings reveal a novel interaction between brain-infiltrated CD8+ T cells and parenchyma cells in the ECM brainstem, suggesting that the PD-1/PD-L1 signal pathway is a promising adjunctive therapeutic strategy for ECM targeting over-activated CD8+ T cells.

Association Between Child Maltreatment and Aggression in Chinese Early Adolescents: The Mediating Role of Irritability.

Child maltreatment (CM) is a major global public health issue, and a strong association exists between CM and aggression. However, the underlying mechanism of this association has not been understood to date. The objective of this study was to explore the mediating role of irritability in the association between CM and aggression in Chinese early adolescents. A cross-sectional study was conducted using a self-report questionnaire to evaluate the levels of CM, aggression, and irritability in 5,724 middle school students from the Anhui Province, China. Structural equation modeling was used to test the hypothesis of the mediating effect of irritability on the relationship between CM and aggression. We further investigated gender differences in this association using multiple group analyses. CM was positively related to both irritability and aggression, and irritability was positively associated with aggression (p < .01). The mediating effects of irritability between CM and aggression were significant (ß = .107, 95% confidence intervals [CI]: 0.077-0.133, p < .05). Males had a higher indirect effect size of the pathway from CM to aggression via irritability compared with females. Overall, irritability was a crucial mediator in the relationship between CM and aggression in Chinese adolescents, and males were more prone to engage in aggression compared with females through the pathway of irritability. Therefore, early irritability characteristics should be carefully monitored in adolescents, and they should be provided adequate support to acquire critical emotion regulation skills.

Mystery of bisphenol F-induced nonalcoholic fatty liver disease-like changes: Roles of Drp1-mediated abnormal mitochondrial fission in lipid droplet deposition.

As one of the major substitutes for bisphenol A (BPA), bisphenol F (BPF) has been widely used. Our previous study demonstrated that BPF exposure facilitates lipid droplet deposition in hepatic cells, contributing to nonalcoholic fatty liver disease (NAFLD)-like changes. However, the underlying mechanisms remain poorly understood. Here, with a metabolic cage system, we observed the perturbation of energy metabolism in mice treated with BPF. BPF obviously suppressed metabolic capacity, which manifested as decreased energy expenditure, low O2 consumption and CO2 levels in mice. Consistent with the in vivo results, a Seahorse XF Cell Mito Stress Test showed significant reductions in mitochondrial ATP production capacity, maximum respiratory capacity, and residual respiratory capacity after BPF treatment in an in vitro study. Electron microscopy revealed a striking increase in mitochondrial fission that was synchronous with excessive expression and activation of dynamin-related protein 1 (Drp1). Intriguingly, chemical inhibition of Drp1 by Mdivi-1 and/or silencing of Drp1 dramatically hampered mitochondrial fission and ameliorated BPF-induced lipid droplet deposition both in mouse liver and human hepatic cells. Mechanistically, mitochondrial dynamics imbalance played prominent roles in these processes, since suppression of Drp1 by chemical inhibition or knockdown substantially reversed BPF-induced mitochondrial fission and ameliorated the suppression of mitochondrial metabolism as well as excessive mitochondrial ROS, which was verified to be key to lipid droplet deposition. Collectively, the findings of the current study reveal previously unrecognized effects involving Drp1-mediated mitochondrial injury in BPF-induced lipid droplet deposition. Therefore, targeted intervention against mitochondrial dysfunction may be a promising therapeutic strategy for BPF-induced NAFLD-like changes.

CodY: An Essential Transcriptional Regulator Involved in Environmental Stress Tolerance in Foodborne Staphylococcus aureus RMSA24.

Staphylococcus aureus (S. aureus), as the main pathogen in milk and dairy products, usually causes intoxication with vomiting and various kinds of inflammation after entering the human body. CodY, an important transcriptional regulator in S. aureus, plays an important role in regulating metabolism, growth, and virulence. However, little is known about the role of CodY on environmental stress tolerance. In this research, we revealed the role of CodY in environmental stress tolerance in foodborne S. aureus RMSA24. codY mutation significantly reduced the tolerance of S. aureus to desiccation and oxidative, salt, and high-temperature stresses. However, S. aureus was more tolerant to low temperature stress due to mutation of codY. We found that the expressions of two important heat shock proteins-GroEL and DanJ-were significantly down-regulated in the mutant codY. This suggests that CodY may indirectly regulate the high- and low-temperature tolerance of S. aureus by regulating the expressions of groEL and danJ. This study reveals a new mechanism of environmental stress tolerance in S. aureus and provides new insights into controlling the contamination and harm caused by S. aureus in the food industry.

Balance-Associated Tests Contribute to Predicting the Need for Ambulatory Assistive Devices (AAD) among Community-Dwelling Older Adults.

This study aims to analyze the use of ambulatory assistive devices (AAD) in relation to balance-associated tests and assist medical staff in providing professional objective reference values for older adults on whether to use AAD. Older adults (n = 228) were recruited from the local community to participate in this study. Participants were divided into the AAD-use group and the non-AAD-use group. Four balance-associated tests and scales were applied to predict the relationship between balance function and the use of AAD in older adults. They were used to assess the participant's balance function and confidence in maintaining balance and were considered the most reliable measures of balance. There were significant differences in the Berg Balance Scale (BBS) score and Timed Up and Go Test (TUGT) among the subjects in the AAD-use group and non-AAD-use group (p < 0.001). The ROC curve analysis presented the following cut-off values for balance tests and scales: 23.62 s for the TUGT test and 41.5 points for the BBS score. For example, if the TUGT score is greater than 23.62 s and the BBS score is below 41.5 points, AAD is recommended for older adults to maintain balance and prevent falls. These objective reference standards may be useful in guiding medical personnel to determine whether older adults need to use AAD. In future studies, we hope to include more participants for subgroup analysis, investigating different types of AAD and their effects on older adults.

Machine learning-assisted fluorescence sensor array for qualitative and quantitative analysis of pyrethroid pesticides.

The simultaneous detection of multiple residues of pyrethroid pesticides (PPs) on vegetables and fruits is still challenging using traditional nanosensing methods due to the high structural similarity of PPs. In this work, sensor arrays composed of three nanocomposite complexes (rhodamine B-CD@Au, rhodamine 6G-CD@Au, and coumarin 6-CD@Au) were constructed to discriminate between structurally similar PPs. Four PPs, deltamethrin, fenvalerate, cyfluthrin, and fenpropathrin, were successfully discriminated. The ability of these sensor units was derived from the different affinity between receptor/analyte and receptor/dye, as well as the non-linear relationship between fluorescence signal and analyte concentration. Upon multivariate pattern recognition analysis, the array performed high-throughput identification of four PPs in unknown samples with 100% classification accuracy. In addition, good accuracy of predicting concentration using the "stepwise prediction" strategy combined with the machine learning method was achieved.

Topology Optimization for Digital Light Projector Additive Manufacturing Addressing the In-Situ Structural Strength Issue.

A topology optimization approach is proposed for the design of self-supporting structures for digital light projector (DLP) 3D printing. This method accounts for the adhesion forces between the print part and the resin base during DLP printing to avoid failure of the part due to stress concentration and weak connections. Specifically, the effect of the process-related adhesion forces is first simulated by developing a design variable-interpolated finite element model to capture the intricate mechanical behavior during DLP 3D printing. Guided by the process model, a stress-constrained topology optimization algorithm is formulated with both the SIMP and RAMP interpolation schemes. The interpolations on the stress term and the design-dependent adhesion load are carefully investigated. A sensitivity result on the P-norm stress constraint is fully developed. Finally, the approach is applied to several 2D benchmark examples to validate its efficacy in controlling the process-caused peak P-norm stresses. The effects of alternating between the SIMP and RAMP interpolations and changing the stress upper limits are carefully explored during the numerical trials. Moreover, 3D printing tests are performed to validate the improvement in printability when involving the process-related P-norm stress constraint.

Coffee consumption and periodontitis: a Mendelian Randomization study.

BACKGROUND: Coffee is one of the most consumed beverages in the world, coffee consumption has been growing in the United States over the past 20 years. Periodontitis is defined by the pathologic loss of the periodontal ligament and destruction of the connective tissue attachment and alveolar bone loss and is related to different systemic diseases and conditions. However, the causality has remained unclarified, thus we regarded discovering the causal relationship between coffee consumption and the liability to periodontitis as the objective of the study. METHODS: Coffee consumption was subdivided into binary coffee consumption and continuous coffee consumption to refine the study design. Genetic instruments were stretched from the MRC-IEU's (MRC Integrative Epidemiology Unit) output from the GWAS pipeline using phesant-derived variables based on the UK Biobank, the Gene-Lifestyle Interactions in Dental Endpoints (GLIDE) project, and the joint meta-analysis of a recent GWAS. The IVW (Inverse Variance Weighted) was regarded as the primary method to estimate the causality, a scatter plot revealed the intuitive result, and tests for stability were also carried out. RESULTS: An effect of continuous coffee consumption on the risk of periodontitis was found, with per SD of coffee consumed increases, the risk of periodontitis rises by 1.04% (Odds Ratio of IVW is 1.0104), while the effect of binary coffee consumption on periodontitis did not meet the requirement of indicating a strong causal association, neither were the reverse causality analyses. CONCLUSIONS: The study indicated the causality of continuous coffee consumption to the risk of periodontitis with a relatively small scale of effect estimate and no strong evidence for an effect of binary coffee-consuming behavior on periodontitis. There was also no intensive evidence suggesting reverse causality.

Description of Tellurirhabdus bombi sp. nov., Isolated from Bumblebee.

A Gram-stain-negative, aerobic, non-motile, and rod-shaped bacterium, designated IE-0392T, was isolated from a bumblebee. The 16S rRNA gene sequence (highest 16S rRNA gene sequence similarity with the type strain of Tellurirhabdus rosea (90.0%) and phylogenetic analysis suggest that strain IE-0392T was a member of the genus Tellurirhabdus. Strain IE-0392T optimally grew at 25 â„ƒ and pH 7.0. Menaquinone 7 (MK-7) was the only isoprenoid quinone present in strain IE-0392T. The major fatty acids (> 10%) of strain IE-0392T were iso-C15:0, C16:1 ω5c, and iso-C17:0 3-OH. The polar lipids of strain IE-0392T were phosphatidylethanolamine, phosphatidylserine, unidentified aminophospholipids, unidentified aminolipid, unidentified phospholipid, and unidentified lipids. The genomic DNA G + C content of strain IE-0392T was 48.8%. The amino acid identity (AAI) and the average nucleotide identity (ANI) values suggest that strain IE-0392T is a novel member of the genus Tellurirhabdus. The results suggest that strain IE-0392T represents a novel species of the genus Tellurirhabdus, for which the name Tellurirhabdus bombi sp. nov., is proposed. The type strain is IE-0392T (= GDMCC 1.2794T = JCM 35040T).

Progress in nanoparticle-based regulation of immune cells.

Immune cells are indispensable defenders of the human body, clearing exogenous pathogens and toxicities or endogenous malignant and aging cells. Immune cell dysfunction can cause an inability to recognize, react, and remove these hazards, resulting in cancers, inflammatory diseases, autoimmune diseases, and infections. Immune cells regulation has shown great promise in treating disease, and immune agonists are usually used to treat cancers and infections caused by immune suppression. In contrast, immunosuppressants are used to treat inflammatory and autoimmune diseases. However, the key to maintaining health is to restore balance to the immune system, as excessive activation or inhibition of immune cells is a common complication of immunotherapy. Nanoparticles are efficient drug delivery systems widely used to deliver small molecule inhibitors, nucleic acid, and proteins. Using nanoparticles for the targeted delivery of drugs to immune cells provides opportunities to regulate immune cell function. In this review, we summarize the current progress of nanoparticle-based strategies for regulating immune function and discuss the prospects of future nanoparticle design to improve immunotherapy.

In vivo quantification of human aqueous veins by enhanced depth imaging optical coherence tomography and optical coherence tomography angiography images.

AIM: To investigate the aqueous vein in vivo by using enhanced depth imaging optical coherence tomography (EDI-OCT) and optical coherence tomography angiography (OCTA). METHODS: In this cross-sectional comparative study, 30 healthy participants were enrolled. Images of the aqueous and conjunctival veins were captured by EDI-OCT and OCTA before and after water loading. The area, height, width, location depth and blood flow of the aqueous vein and conjunctival vein were measured by Image J software. RESULTS: In the static state, the area of the aqueous vein was 8166.7±3272.7 µm2, which was smaller than that of the conjunctival vein (13 690±7457 µm2, P<0.001). The mean blood flow density of the aqueous vein was 35.3%±12.6%, which was significantly less than that of the conjunctival vein (51.5%±10.6%, P<0.001). After water loading, the area of the aqueous vein decreased significantly from 8725.8±779.4 µm2 (baseline) to 7005.2±566.2 µm2 at 45min but rose to 7863.0±703.2 µm2 at 60min (P=0.032). The blood flow density of the aqueous vein decreased significantly from 41.2%±4.5% (baseline) to 35.4%±3.2% at 30min but returned to 45.6%±3.6% at 60min (P=0.021). CONCLUSION: The structure and blood flow density of the aqueous vein can be effectively evaluated by OCT and OCTA. These may become biological indicators to evaluate aqueous vein changes and aqueous outflow resistance under different interventions in glaucoma patients.

Multi-scale Efficient Graph-Transformer for Whole Slide Image Classification.

The multi-scale information among the whole slide images (WSIs) is essential for cancer diagnosis. Although the existing multi-scale vision Transformer has shown its effectiveness for learning multi-scale image representation, it still cannot work well on the gigapixel WSIs due to their extremely large image sizes. To this end, we propose a novel Multi-scale Efficient Graph-Transformer (MEGT) framework for WSI classification. The key idea of MEGT is to adopt two independent efficient Graph-based Transformer (EGT) branches to process the low-resolution and high-resolution patch embeddings (i.e., tokens in a Transformer) of WSIs, respectively, and then fuse these tokens via a multi-scale feature fusion module (MFFM). Specifically, we design an EGT to efficiently learn the local-global information of patch tokens, which integrates the graph representation into Transformer to capture spatial-related information of WSIs. Meanwhile, we propose a novel MFFM to alleviate the semantic gap among different resolution patches during feature fusion, which creates a non-patch token for each branch as an agent to exchange information with another branch by cross-attention mechanism. In addition, to expedite network training, a new token pruning module is developed in EGT to reduce the redundant tokens. Extensive experiments on both TCGA-RCC and CAMELYON16 datasets demonstrate the effectiveness of the proposed MEGT.