Design, Synthesis, and Anti-Hepatocellular Carcinoma Evaluation of Sesquiterpene Lactone Epimers Trilobolide-6-O-isobutyrate Analogs.

Hepatocellular carcinoma (HCC), one of the most common malignant cancers with a low 5-year survival rate, is the third leading cause of cancer-related deaths worldwide. The finding of novel agents and strategies for the treatment of HCC is an urgent need. Sesquiterpene lactones (SLs) have attracted extensive attention because of their potent antitumor activity. In this study, a new series of SL derivatives (3-18) were synthesized using epimers 1 and 2 as parent molecules, isolated from Sphagneticola trilobata, and evaluated for their anti-HCC activity. Furthermore, the structures of 4, 6, and 14 were confirmed by X-ray single-crystal diffraction analyses. The cytotoxic activities of 3-18 on two HCC cell lines, including HepG2 and Huh7, were evaluated using the CCK-8 assay. Among them, compound 10 exhibited the best activity against the HepG2 and Huh7 cell lines. Further studies showed that 10 induced cell apoptosis, arrested the cell cycle at the S phase, and induced the inhibition of cell proliferation and migration in HepG2 and Huh7. In addition, absorption, distribution, metabolism, and excretion (ADME) properties prediction showed that 10 may possess the properties to be a drug candidate. Thus, 10 may be a promising lead compound for the treatment of HCC.

Taxifolin ameliorates sepsis-induced lung capillary leak through inhibiting the JAK/STAT3 pathway.

BACKGROUND: As a systemic inflammatory reaction, sepsis is associated with various organ dysfunctions. The capillary leakage and the imbalance between T helper 17 and regulatory T (Th17/Treg) cells are associated with sepsis-induced lung injury. Taxifolin (TXL) has been found to play a vital role in regulating this diverse disease. However, the detailed functioning and mechanism of TXL in regulating sepsis-induced lung capillary leak remain elusive. METHODS: Balb/c mice were used to establish sepsis-induced lung injury model through administration of lipopolysaccharide (LPS). The structure of lung tissues was observed by using hematoxylin & eosin staining. Protein level and total cells in bronchoalveolar lavage fluid (BALF) were measured by bicinchoninic acid (BCA) protein assay kit and hematimetry assay, respectively. Quantitative real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay were employed to detect the level of inflammatory cytokines. The content of Th17 and Treg cells were measured by flow cytometry analysis. Western blot assay was used to determine the protein level of retinoid-related orphan receptor-γt (RORγt), Forkhead box P3 (Foxp3), Janus kinase 2 (JAK2), phospho(p)-JAK2, signal transducer and activator of transcription 3 (STAT3), and phospho(p)-STAT3. RESULTS: Taxifolin effectively prolonged the survival period of sepsis mice and alleviated LPS-induced lung injury in a dose-dependent manner. Moreover, TXL reduced LPS-induced increase in protein levels and T cell content in BALF, and effectively restored the wet:dry ratio of lung tissue and tissue permeability. Treating with TXL notably inhibited the production of pro-inflammatory cytokines induced by sepsis and influenced the balance between Th17 and Treg cells. Furthermore, TXL treatment suppressed the activation of JAK/STAT3 signaling pathway in a dose-dependent manner. CONCLUSION: Our findings revealed that TXL alleviated sepsis-induced capillary leak in the lungs of mice by regulating JAK/STAT3 signaling pathway.

Optical thin-film filter design with Bragg pair constraint and a divide-and-conquer approach for reduction of the Brewster hole.

Bragg pairs are used as fundamental units to realize optimized thin-film structures. This method is efficient in designing for a large number of layers, such as in a bandpass filter or an edge filter with a relatively wide stopband or angular range. It adapts readily to conventional optimization methodology (such as genetic algorithms). In this paper, the method is first illustrated by application to a conventional high-pass coating on glass, using one set of Bragg pair materials. This demonstrated a 10% improvement over an alternative design technique. A second example is demonstrated using two sets of Bragg pair materials, designed with a more complex merit function, to increase the reflectance around the Brewster angle for p-polarized light. This demonstrated a 19% average reflection improvement across the stopband compared to a two-material design.

Surgical management of benign phyllodes tumours of the breast: Is wide local excision really necessary?

SUMMARY: Current guidelines recommending wide local excision (≥ 1 cm margin) for all breast phyllodes tumours regardless of classification are based on retrospective data. Benign phyllodes tumours of the breast are not aggressive. They are often indistinguishable from fibroadenomas on core biopsy and are diagnosed only after excisions without attention to margins. Once the diagnosis is made, the decision to operate and obtain further margins versus wait-and-watch is the dilemma breast surgeons face on a regular basis.

Apoptosis in human myelodysplastic syndrome CD34+ cells is modulated by the upregulation of TLRs and histone H4 acetylation via a ß-arrestin 1 dependent mechanism.

Excessive apoptosis of hematopoietic precursors in the bone marrow underlies the ineffective hematopoiesis characteristic of myelodysplastic syndrome (MDS). Toll-like receptor (TLR) signaling is abnormally activated in MDS and may be involved in excessive programmed cell death in the pathogenesis of MDS. TLRs expression and global histone H3/H4 acetylation were analyzed in bone marrow (BM) CD34+ cells from 20 lower-risk and 20 higher-risk MDS patients and 10 healthy controls. Apoptosis of BM CD34+ cells was examined by flow cytometry, and its correlation to histone acetylation and the expression of TLR2 and ß-arrestin1 (ß-arr1), measured by enzyme-linked immunosorbent assay and qRT-PCR, was assessed. TLR1, TLR2 and TLR6 expression and H4 acetylation levels were higher in lower-risk MDS patients than in higher-risk MDS patients or controls, and TLR2 expression and H4 acetylation levels were positively correlated with an increased rate of apoptosis. Lower-risk MDS was associated with increased ß-arr1 expression and histone acetyltransferase p300 activity. In in vitro-cultured primary normal and lower-risk MDS CD34+ cells, TLR2 activation-induced apoptosis was mediated by the upregulation of ß-arr1 leading to the recruitment of p300 and increased histone H4 acetylation. The nuclear accumulation of ßarr1 following TLR2 activation promote H4 acetylation at specific target gene promoters and may thus affect transcription of target genes in BM CD34+ cells. The mechanisms underlying the deregulation of TLR2 and increased apoptosis in MDS may involve the ß-arr1 mediated recruitment of p300 leading to increased levels of histone H4 acetylation.

Learning to Recover Spectral Reflectance From RGB Images.

This paper tackles spectral reflectance recovery (SRR) from RGB images. Since capturing ground-truth spectral reflectance and camera spectral sensitivity are challenging and costly, most existing approaches are trained on synthetic images and utilize the same parameters for all unseen testing images, which are suboptimal especially when the trained models are tested on real images because they never exploit the internal information of the testing images. To address this issue, we adopt a self-supervised meta-auxiliary learning (MAXL) strategy that fine-tunes the well-trained network parameters with each testing image to combine external with internal information. To the best of our knowledge, this is the first work that successfully adapts the MAXL strategy to this problem. Instead of relying on naive end-to-end training, we also propose a novel architecture that integrates the physical relationship between the spectral reflectance and the corresponding RGB images into the network based on our mathematical analysis. Besides, since the spectral reflectance of a scene is independent to its illumination while the corresponding RGB images are not, we recover the spectral reflectance of a scene from its RGB images captured under multiple illuminations to further reduce the unknown. Qualitative and quantitative evaluations demonstrate the effectiveness of our proposed network and of the MAXL. Our code and data are available at https://github.com/Dong-Huo/SRR-MAXL.

Deguelin inhibits the glioblastoma progression through suppressing CCL2/NFκB signaling pathway.

Glioblastoma multiforme (GBM) is the most common primary intracranial tumor with characteristics of high aggressiveness and poor prognosis. Deguelin, a component from the bark of Leguminosae Mundulea sericea (African plant), displays antiproliferative effects in some tumors, however, the inhibitory effect and mechanism of deguelin on GBM were still poorly understood. At first, we found that deguelin reduced the viability of GBM cells by causing cell cycle arrest in G2/M phase and inducing their apoptosis. Secondly, deguelin inhibited the migration of GBM cells. Next, RNA-seq analysis identified that CCL2 (encoding chemokine CCL2) was downregulated significantly in deguelin-treated GBM cells. As reported, CCL2 promoted the cell growth, and CCL2 was associated with regulating NFκB signaling pathway, as well as involved in modulating tumor microenvironment (TME). Furthermore, we found that deguelin inactivated CCL2/NFκB signaling pathway, and exougous CCL2 could rescue the anti-inhibitory effect of deguelin on GBM cells via upregulating NFκB. Finally, we established a syngeneic intracranial orthotopic GBM model and found that deguelin regressed the tumor growth, contributed to an anti-tumorigenic TME and inhibited angiogenesis of GBM by suppressing CCL2/NFκB in vivo. Taken together, these results suggest the anti-GBM effect of deguelin via inhibiting CCL2/NFκB pathway, which may provide a new strategy for the treatment of GBM.

Sophocarpine inhibits the progression of glioblastoma via PTEN/PI3K/Akt signaling pathway.

Glioblastoma multiforme (GBM) is the most fatal primary brain tumor which lacks effective treatment drugs. Alkaloids are known as a class of potential anti-tumor agents. Sophocarpine, a tetracyclic quinazoline alkaloid derived from Sophora alopecuroides L., possesses several pharmacological effects including anti-tumor effects in some malignancies. However, the effect and mechanism of sophocarpine on GBM remains to be explored. In this study, based on in vitro experiments, we found that sophocarpine significantly inhibited the viability, proliferation and migration of GBM cells including U251 and C6 cells in a dose- and time-dependent manner. Besides, sophocarpine arrested GBM cell cycle in G0/G1 phase and induced their apoptosis. Subsequently, we found that sophocarpine upregulated the expression of PTEN, a GBM tumor suppressor, and downregulated PI3K/Akt signaling in GBM cells. Moreover, inactivating of PTEN with bpV(phen) trihydrate partially restored the anti-GBM effects of sophocarpine via PI3K/Akt signaling. Finally, sophocarpine significantly inhibited the growth of tumor both in subcutaneous and orthotopic U251 xenograft GBM model in nude mice via PTEN/PI3K/Akt axis. Taken together, these results suggested that sophocarpine impeded GBM progression via PTEN/PI3K/Akt axis both in vitro and in vivo, providing with a promising therapy for treating GBM.

Pubertal timing in adolescence and adulthood: Relations among contemporaneous and retrospective measures.

Pubertal development has short- and long-term effects on psychological adjustment. Many studies of long-term effects rely on retrospective measurement of pubertal timing, but such measures often reflect different aspects of puberty than those assessed in adolescence, raising questions about the utility and interpretation of retrospective reports. The present study leveraged longitudinal data collected in adolescence and established adulthood to determine: (1) the correspondence between pubertal timing indexed from logistic growth curves of self-reported physical development assessed contemporaneously across adolescence and pubertal timing indexed relative to peers assessed retrospectively in adulthood; (2) the associations between the two pubertal timing measures and psychological adjustment; and (3) potential recall biases. Participants were 748 individuals (50.1% female; 91.6% White) from two longitudinal studies who reported on their pubertal development annually from Grades 3-9, psychological adjustment (age at sexual initiation, substance use, depression) in late adolescence, and retrospective pubertal timing in established adulthood (Mage = 32.76; SD = 4.43). Results indicate moderate-to-high convergence between retrospective and contemporaneous indices. Most participants, especially women, had the same pubertal timing classification (i.e., early, on time, or late), but early-maturing adolescents often recalled on-time development as adults. Retrospective and contemporaneous indices were associated with psychological adjustment in similar ways, with some attenuation in the retrospective measure, especially for men. There was little evidence of recall bias due to age at retrospective assessment or time since puberty. Findings generally support the use of retrospective pubertal timing measures, with the recognition that some relations with adjustment may be weakened. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Effect of the combination of he-sea and front-mu points on enteral nutrition feeding intolerance in critical illness patients. / åˆå‹Ÿé ç©´æ²»ç–—å±é‡ç—‡æ‚£è€ è‚ å† è¥å »å–‚å »ä¸è€å—çš„ç–—æ•ˆè§‚å¯Ÿ.

OBJECTIVES: To explore the effects of the combination of he-sea and front-mu points on the feeding compliance rate, the intra-abdominal pressure, the enteral nutrition tolerance score, the score of acute physiological and chronic health evaluation (APACHE)-Ⅱ and gastrointestinal function impairment grade in the patients with enteral nutrition feeding intolerance (ENFI) of critical illness and evaluate clinical effect on ENFI after acupuncture at the he-sea and front-mu points. METHODS: Seventy patients of ENFI were randomized into a control group and an observation group, 35 cases in each one. In the control group, the patients were treated with routine regimen combined with intestinal nutrition support. In the observation group, on the basis of the treatment as the control group, acupuncture was applied to Shangwan (CV13), Zhongwan (CV12), Xiawan (CV10), Qihai (CV6) and Guanyuan (CV4), as well as bila-teral Neiguan (PC6), Zusanli (ST36), Xiajuxu (ST39), Shangjuxu (ST37), Tianshu (ST25) and Daheng (SP15). Of those acupoints, ST25 and SP15 on the same side were attached to one pair of electrodes (20 Hz/100 Hz). Acupuncture was delivered once daily, 30 min each time and for consecutive 7 days. During treatment, the numbers of the cases up to the feeding standard were observed everyday to calculate the feeding compliance rate. The score of enteral nutrition tolerance, the intra-abdominal pressure, the score of APACHE-Ⅱ and the level of acute gastriointestinal injury(AGI) grading were recorded. RESULTS: After treatment, the enteral feeding compliance rate was increased in comparison with that before treatment in the two groups, and the rate in the observation group was higher than that of the control group (P<0.05) except that on the 2nd day. The score of the enteral nutrition tolerance, the intra-abdominal pressure, the score of APACHE-Ⅱ and the level of AGI were all reduced (P<0.05, P<0.01) when compared with those before treatment in the two groups, and these indicators in the observation group were lower (P<0.05) than those of the control group. CONCLUSIONS: Acupuncture at the he-sea and front-mu points relieves the conditions of ENFI, improves the feeding and the recovery of gastrointestinal function, and benefits the prognosis through increasing the amount of enteral nutrition in ENFI patients.

Columbianadin suppresses glioblastoma progression by inhibiting the PI3K-Akt signaling pathway.

Glioblastoma (GBM) is the most common malignant glioma among brain tumors with low survival rate and high recurrence rate. Columbianadin (CBN) has pharmacological properties such as anti-inflammatory, analgesic, thrombogenesis-inhibiting and anti-tumor effects. However, it remains unknown that the effect of CBN on GBM cells and its underlying molecular mechanisms. In the present study, we found that CBN inhibited the growth and proliferation of GBM cells in a dose-dependent manner. Subsequently, we found that CBN arrested the cell cycle in G0/G1 phase and induced the apoptosis of GBM cells. In addition, CBN also inhibited the migration and invasion of GBM cells. Mechanistically, we chose network pharmacology approach by screening intersecting genes through targets of CBN in anti-GBM, performing PPI network construction followed by GO analysis and KEGG analysis to screen potential candidate signaling pathway, and found that phosphatidylinositol 3-kinase/Protein Kinase-B (PI3K/Akt) signaling pathway was a potential target signaling pathway of CBN in anti-GBM. As expected, CBN treatment indeed inhibited the PI3K/Akt signaling pathway in GBM cells. Furthermore, YS-49, an agonist of PI3K/Akt signaling, partially restored the anti-GBM effect of CBN. Finally, we found that CBN inhibited GBM growth in an orthotopic mouse model of GBM through inhibiting PI3K/Akt signaling pathway. Together, these results suggest that CBN has an anti-GBM effect by suppressing PI3K/Akt signaling pathway, and is a promising drug for treating GBM effectively.

Pharmacological targeting cGAS/STING/NF-κB axis by tryptanthrin induces microglia polarization toward M2 phenotype and promotes functional recovery in a mouse model of spinal cord injury.

ABSTRACT: The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury. Regulation of shifting microglia polarization from M1 (neurotoxic and proinflammatory type) to M2 (neuroprotective and anti-inflammatory type) after spinal cord injury appears to be crucial. Tryptanthrin possesses an anti-inflammatory biological function. However, its roles and the underlying molecular mechanisms in spinal cord injury remain unknown. In this study, we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in vitro. Tryptanthrin promoted M2 polarization through inactivating the cGAS/STING/NF-κB pathway. Additionally, we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury, inhibited neuronal loss, and promoted tissue repair and functional recovery in a mouse model of spinal cord injury. Finally, using a conditional co-culture system, we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal apoptosis. Taken together, these results suggest that by targeting the cGAS/STING/NF-κB axis, tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.

Dual targeting agent Thiotert inhibits the progression of glioblastoma by inducing ER stress-dependent autophagy.

Glioblastoma (GBM) is the most aggressive and lethal type of tumor in the central nervous system, characterized by a high incidence and poor prognosis. Thiotert, as a novel dual targeting agent, has potential inhibitory effects on various tumors. Here, we found that Thiotert effectively inhibited the proliferation of GBM cells by inducing G2/M cell cycle arrest and suppressed the migratory ability in vitro. Furthermore, Thiotert disrupted the thioredoxin (Trx) system while causing cellular DNA damage, which in turn caused endoplasmic reticulum (ER) stress-dependent autophagy. Knockdown of ER stress-related protein ATF4 in U251 cells inhibited ER stress-dependent autophagy caused by Thiotert to some extent. Orthotopic transplantation experiments further showed that Thiotert had the same anti-GBM activity and mechanism as in vitro. Conclusively, these results suggest that Thiotert induces ER stress-dependent autophagy in GBM cells by disrupting redox homeostasis and causing DNA damage, which provides new insight for the treatment of GBM.

Tenacissoside H repressed the progression of glioblastoma by inhibiting the PI3K/Akt/mTOR signaling pathway.

Glioblastoma (GBM) is one of the most common intracranial primary malignancies with the highest mortality rate, and there is a lack of effective treatments. In this study, we examined the anti-GBM activity of Tenacissoside H (TH), an active component isolated from the traditional Chinese medicine Marsdenia tenacissima (Roxb.) Wight & Arn (MT), and investigated the potential mechanism. Firstly, we found that TH decreased the viability of GBM cells by inducing cell cycle arrest and apoptosis, and inhibited the migration of GBM cells. Furthermore, combined with the Gene Expression Omnibus database (GEO) and network pharmacology as well as molecular docking, TH was shown to inhibit GBM progression by directly regulating the PI3K/Akt/mTOR pathway, which was further validated in vitro. In addition, the selective PI3K agonist 740 y-p partially restored the inhibitory effects of TH on GBM cells. Finally, TH inhibited GBM progression in an orthotopic transplantation model by inactivating the PI3K/Akt/mTOR pathway in vivo. Conclusively, our results suggest that TH represses GBM progression by inhibiting the PI3K/Akt/mTOR signaling pathway in vitro and in vivo, and provides new insight for the treatment of GBM patients.

Glass Segmentation with RGB-Thermal Image Pairs.

This paper proposes a new glass segmentation method utilizing paired RGB and thermal images. Due to the large difference between the transmission property of visible light and that of the thermal energy through the glass where most glass is transparent to the visible light but opaque to thermal energy, glass regions of a scene are made more distinguishable with a pair of RGB and thermal images than solely with an RGB image. To exploit such a unique property, we propose a neural network architecture that effectively combines an RGB-thermal image pair with a new multi-modal fusion module based on attention, and integrate CNN and transformer to extract local features and non-local dependencies, respectively. As well, we have collected a new dataset containing 5551 RGB-thermal image pairs with ground-truth segmentation annotations. The qualitative and quantitative evaluations demonstrate the effectiveness of the proposed approach on fusing RGB and thermal data for glass segmentation. Our code and data are available at https://github.com/Dong-Huo/RGB-T-Glass-Segmentation.

Attention Load Regulates the Facilitation of Audio-Visual Information on Landing Perception in Badminton.

Based on the role of the high temporal sensitivity of the auditory modality and the advantage of audio-visual integration in motion perception and anticipation, we investigated the effect of audio-visual information on landing perception in badminton through two experiments; and we explored the regulatory role of attention load. In this study, experienced badminton players were asked to predict the landing position of the shuttle under the conditions of video (visual) or audio-video (audio-visual) presentation. We manipulated flight information or attention load. The results of Experiment 1 showed that, whether the visual information was rich or not, that is, whether or not it contained the early flight trajectory, the addition of auditory information played a promoting role. The results of Experiment 2 showed that attention load regulated the facilitation of multi-modal integration on landing perception. The facilitation of audio-visual information was impaired under high load, meaning that audio-visual integration tended to be guided by attention from top to bottom. The results support the superiority effect of multi-modal integration, suggesting that adding auditory perception training to sports training could significantly improve athletes' performance.

HIPA: Hierarchical Patch Transformer for Single Image Super Resolution.

Transformer-based architectures start to emerge in single image super resolution (SISR) and have achieved promising performance. However, most existing vision Transformer-based SISR methods still have two shortcomings: (1) they divide images into the same number of patches with a fixed size, which may not be optimal for restoring patches with different levels of texture richness; and (2) their position encodings treat all input tokens equally and hence, neglect the dependencies among them. This paper presents a HIPA, which stands for a novel Transformer architecture that progressively recovers the high resolution image using a hierarchical patch partition. Specifically, we build a cascaded model that processes an input image in multiple stages, where we start with tokens with small patch sizes and gradually merge them to form the full resolution. Such a hierarchical patch mechanism not only explicitly enables feature aggregation at multiple resolutions but also adaptively learns patch-aware features for different image regions, e.g., using a smaller patch for areas with fine details and a larger patch for textureless regions. Meanwhile, a new attention-based position encoding scheme for Transformer is proposed to let the network focus on which tokens should be paid more attention by assigning different weights to different tokens, which is the first time to our best knowledge. Furthermore, we also propose a multi-receptive field attention module to enlarge the convolution receptive field from different branches. The experimental results on several public datasets demonstrate the superior performance of the proposed HIPA over previous methods quantitatively and qualitatively. We will share our code and models when the paper is accepted.

Lesion mimic mutant 8 balances disease resistance and growth in rice.

Lesion-mimic mutants (LMM) spontaneously produce necrotic spots, a process not affected by environmental stress or pathogen infection. In this study, we identified a LMM, lesion mimic mutant 8 (lmm8) in rice (Oryza sativa). The lmm8 mutant produces brown and off-white lesions on its leaves during the second- and third-leaf stages. The lesion mimic phenotype of the lmm8 mutant was enhanced by light. At the mature stage, lmm8 mutant are shorter and exhibit inferior agronomic traits than the wild type. Contents of photosynthetic pigments and chloroplast fluorescence were significantly reduced in lmm8 leaves, along with increased production of reactive oxygen species and programmed cell death compared to the wild type. The mutated gene was identified as LMM8 (LOC_Os01g18320) by map-based cloning. A point mutation occurred in LMM8, causing a Leu to Arg mutation of the 146th amino acid of LMM8. It is an allele of SPRL1, encoding a protoporphyrinogen IX oxidase (PPOX) located in chloroplasts and involved in the biosynthesis of tetrapyrrole in chloroplasts. The lmm8 mutant showed enhanced resistance and broad-spectrum resistance. Together, our results demonstrate the importance of rice LMM8 protein in defense responses and plant growth in rice, and provides theoretical support for resistance breeding to improve rice yield.

Angelicin impedes the progression of glioblastoma via inactivation of YAP signaling pathway.

Glioblastoma (GBM) is a human malignant tumor with low survival and high recurrence rate. Angelicin, an active furanocoumarin compound, has been reported to possess potential antitumor activity towards various malignancies. However, the effect of angelicin on GBM cells and its mechanism are still unclear. In this study, we found that angelicin inhibited the proliferation of GBM by inducing the cell cycle arrested in G1 phase and suppressed the migration of GBM cells in vitro. Mechanically, we found that angelicin downregulated the expression of YAP and decreased the nuclear localization of YAP, and suppressed the expression of ß-catenin. Furthermore, overexpression of YAP partially restored the inhibitory effect of angelicin on GBM cells in vitro. Finally, we found that angelicin could inhibit the growth of tumor and reduce the expression of YAP in the subcutaneous xenograft model of GBM in nude mice and the syngeneic intracranial orthotopic model of GBM in C57BL/6 mice. Taken together, our results suggest that the natural product angelicin exerts its anticancer effects on GBM via YAP signaling pathway, and is expected to be a promising compound for the treatment of GBM.

Uncertainty-inspired open set learning for retinal anomaly identification.

Failure to recognize samples from the classes unseen during training is a major limitation of artificial intelligence in the real-world implementation for recognition and classification of retinal anomalies. We establish an uncertainty-inspired open set (UIOS) model, which is trained with fundus images of 9 retinal conditions. Besides assessing the probability of each category, UIOS also calculates an uncertainty score to express its confidence. Our UIOS model with thresholding strategy achieves an F1 score of 99.55%, 97.01% and 91.91% for the internal testing set, external target categories (TC)-JSIEC dataset and TC-unseen testing set, respectively, compared to the F1 score of 92.20%, 80.69% and 64.74% by the standard AI model. Furthermore, UIOS correctly predicts high uncertainty scores, which would prompt the need for a manual check in the datasets of non-target categories retinal diseases, low-quality fundus images, and non-fundus images. UIOS provides a robust method for real-world screening of retinal anomalies.