Rice false smut virulence protein subverts host chitin perception and signaling at lemma and palea for floral infection.

The flower-infecting fungus Ustilaginoidea virens causes rice false smut, which is a severe emerging disease threatening rice (Oryza sativa) production worldwide. False smut not only reduces yield, but more importantly produces toxins on grains, posing a great threat to food safety. U. virens invades spikelets via the gap between the 2 bracts (lemma and palea) enclosing the floret and specifically infects the stamen and pistil. Molecular mechanisms for the U. virens-rice interaction are largely unknown. Here, we demonstrate that rice flowers predominantly employ chitin-triggered immunity against U. virens in the lemma and palea, rather than in the stamen and pistil. We identify a crucial U. virens virulence factor, named UvGH18.1, which carries glycoside hydrolase activity. Mechanistically, UvGH18.1 functions by binding to and hydrolyzing immune elicitor chitin and interacting with the chitin receptor CHITIN ELICITOR BINDING PROTEIN (OsCEBiP) and co-receptor CHITIN ELICITOR RECEPTOR KINASE1 (OsCERK1) to impair their chitin-induced dimerization, suppressing host immunity exerted at the lemma and palea for gaining access to the stamen and pistil. Conversely, pretreatment on spikelets with chitin induces a defense response in the lemma and palea, promoting resistance against U. virens. Collectively, our data uncover a mechanism for a U. virens virulence factor and the critical location of the host-pathogen interaction in flowers and provide a potential strategy to control rice false smut disease.

Desflurane improves electrical activity of neurons and alleviates oxygen-glucose deprivation-induced neuronal injury by activating the Kcna1-dependent Kv1.1 channel.

Several volatile anesthetics have presented neuroprotective functions in ischemic injury. This study investigates the effect of desflurane (Des) on neurons following oxygen-glucose deprivation (OGD) challenge and explores the underpinning mechanism. Mouse neurons HT22 were subjected to OGD, which significantly reduced cell viability, increased lactate dehydrogenase release, and promoted cell apoptosis. In addition, the OGD condition increased oxidative stress in HT22 cells, as manifested by increased ROS and MDA contents, decreased SOD activity and GSH/GSSG ratio, and reduced nuclear protein level of Nrf2. Notably, the oxidative stress and neuronal apoptosis were substantially blocked by Des treatment. Bioinformatics suggested potassium voltage-gated channel subfamily A member 1 (Kcna1) as a target of Des. Indeed, the Kcna1 expression in HT22 cells was decreased by OGD but restored by Des treatment. Artificial knockdown of Kcna1 negated the neuroprotective effects of Des. By upregulating Kcna1, Des activated the Kv1.1 channel, therefore enhancing K+ currents and inducing neuronal repolarization. Pharmacological inhibition of the Kv1.1 channel reversed the protective effects of Des against OGD-induced injury. Collectively, this study demonstrates that Des improves electrical activity of neurons and alleviates OGD-induced neuronal injury by activating the Kcna1-dependent Kv1.1 channel.

Long term survival outcomes of surgery combined with hyperthermic intraperitoneal chemotherapy for perforated low-grade appendiceal mucinous neoplasms: A multicenter retrospective study.

BACKGROUND: Low-grade appendiceal mucinous neoplasms (LAMN) are very rare, accounting for approximately 0.2%-0.5% of gastrointestinal tumors. We conducted a multicenter retrospective study to explore the impact of different surgical procedures combined with HIPEC on the short-term outcomes and long-term survival of patients. METHODS: We retrospectively analyzed the clinicopathological data of 91 LAMN perforation patients from 9 teaching hospitals over a 10-year period, and divided them into HIPEC group and non-HIPEC group based on whether or not underwent HIPEC. RESULTS: Of the 91 patients with LAMN, 52 were in the HIPEC group and 39 in the non-HIPEC group. The Kaplan-Meier method predicted that 52 patients in the HIPEC group had 5- and 10-year overall survival rates of 82.7% and 76.9%, respectively, compared with predicted survival rates of 51.3% and 46.2% for the 39 patients in the non-HIPEC group, with a statistically significant difference between the two groups (χ2 = 10.622, p = 0.001; χ2 = 10.995, p = 0.001). Compared to the 5-year and 10-year relapse-free survival rates of 75.0% and 65.4% in the HIPEC group, respectively, the 5-year and 10-year relapse-free survival rates of 48.7% and 46.2% in the non-HIPEC group were significant different between the two outcomes (χ2 = 8.063, p = 0.005; χ2 = 6.775, p = 0.009). The incidence of postoperative electrolyte disturbances and hypoalbuminemia was significantly higher in the HIPEC group than in the non-HIPEC group (p = 0.023; p = 0.044). CONCLUSIONS: This study shows that surgery combined with HIPEC can significantly improve 5-year and 10-year overall survival rates and relapse-free survival rates of LAMN perforation patients, without affecting their short-term clinical outcomes.

Action Recognition Based on Multi-Level Topological Channel Attention of Human Skeleton.

In action recognition, obtaining skeleton data from human poses is valuable. This process can help eliminate negative effects of environmental noise, including changes in background and lighting conditions. Although GCN can learn unique action features, it fails to fully utilize the prior knowledge of human body structure and the coordination relations between limbs. To address these issues, this paper proposes a Multi-level Topological Channel Attention Network algorithm: Firstly, the Multi-level Topology and Channel Attention Module incorporates prior knowledge of human body structure using a coarse-to-fine approach, effectively extracting action features. Secondly, the Coordination Module utilizes contralateral and ipsilateral coordinated movements in human kinematics. Lastly, the Multi-scale Global Spatio-temporal Attention Module captures spatiotemporal features of different granularities and incorporates a causal convolution block and masked temporal attention to prevent non-causal relationships. This method achieved accuracy rates of 91.9% (Xsub), 96.3% (Xview), 88.5% (Xsub), and 90.3% (Xset) on NTU-RGB+D 60 and NTU-RGB+D 120, respectively.

A novel automatic segmentation method directly based on magnetic resonance imaging K-space data for auxiliary diagnosis of glioma.

Background: The use of segmentation architectures in medical imaging, particularly for glioma diagnosis, marks a significant advancement in the field. Traditional methods often rely on post-processed images; however, key details can be lost during the fast Fourier transformation (FFT) process. Given the limitations of these techniques, there is a growing interest in exploring more direct approaches. The adaption of segmentation architectures originally designed for road extraction for medical imaging represents an innovative step in this direction. By employing K-space data as the modal input, this method completely eliminates the information loss inherent in FFT, thereby potentially enhancing the precision and effectiveness of glioma diagnosis. Methods: In the study, a novel architecture based on a deep-residual U-net was developed to accomplish the challenging task of automatically segmenting brain tumors from K-space data. Brain tumors from K-space data with different under-sampling rates were also segmented to verify the clinical application of our method. Results: Compared to the benchmarks set in the 2018 Brain Tumor Segmentation (BraTS) Challenge, our proposed architecture had superior performance, achieving Dice scores of 0.8573, 0.8789, and 0.7765 for the whole tumor (WT), tumor core (TC), and enhanced tumor (ET) regions, respectively. The corresponding Hausdorff distances were 2.5649, 1.6146, and 2.7187 for the WT, TC, and ET regions, respectively. Notably, compared to traditional image-based approaches, the architecture also exhibited an improvement of approximately 10% in segmentation accuracy on the K-space data at different under-sampling rates. Conclusions: These results show the superiority of our method compared to previous methods. The direct performance of lesion segmentation based on K-space data eliminates the time-consuming and tedious image reconstruction process, thus enabling the segmentation task to be accomplished more efficiently.

Tumor microenvironment remodeling plus immunotherapy could be used in mesenchymal-like tumor with high tumor residual and drug resistant rate.

Epithelial-mesenchymal transition (EMT) is a common process during tumor progression and is always related to residual tumor, drug resistance and immune suppression. However, considering the heterogeneity in EMT process, there is still a need to establish robust EMT classification system with reasonable molecular, biological and clinical implications to investigate whether these unfavorable survival factors are common or unique in different individuals. In our work, we classify tumors with four EMT status, that is, EMTlow, EMTmid, EMThigh-NOS (Not Otherwise Specified), and EMThigh-AKT (AKT pathway overactivation) subtypes. We find that EMThigh-NOS subtype is driven by intrinsic somatic alterations. While, EMThigh-AKT subtype is maintained by extrinsic cellular interplay between tumor cells and macrophages in an AKT-dependent manner. EMThigh-AKT subtype is both unresectable and drug resistant while EMThigh-NOS subtype can be treated with cell cycle related drugs. Importantly, AKT activation in EMThigh-AKT not only enhances EMT process, but also contributes to the immunosuppressive microenvironment. By remodeling tumor immune-microenvironment by AKT inhibition, EMThigh-AKT can be treated by immune checkpoint blockade therapies. Meanwhile, we develop TumorMT website ( http://tumormt.neuroscience.org.cn/ ) to apply this EMT classification and provide reasonable therapeutic guidance.

TNF-alpha increases angiogenic potential in a co-culture system of dental pulp cells and endothelial cells

Abstract We recently demonstrated that a co-culture system of human umbilical vein endothelial cells (HUVECs) and human dental pulp stem cells (hDPSCs) could enhance angiogenesis ability in vitro. However, whether tumor necrosis factor α (TNF-α) could promote blood vessel formation during pulp regeneration remained unknown. The aim of this study was to investigate the effects of TNF-α on the formation of endothelial tubules and vascular networks in a co-culture system of hDPSCs and HUVECs. hDPSCs were co-cultured with HUVECs at a ratio of 1:5. The Matrigel assay was performed to detect the total tubule branching lengths and numbers of branches, and the Cell-Counting Kit 8 assay was performed to examine the effect of TNF-α on cell proliferation. Real-time polymerase chain reactions and western blot were used to detect vascular endothelial growth factor (VEGF) mRNA and protein expression. The Matrigel assay showed significantly greater total branching lengths and numbers of branches formed in the experimental groups treated with different concentrations of TNF-α compared with the control group. The decomposition times of the tubule structures were also significantly prolonged (P < 0.05). Treatment with 50 ng/ml TNF-α did not significantly change the proliferation of co-cultured cells, but it significantly increased the VEGF mRNA and protein expression levels (p < 0.05). In addition, the migration abilities of HUVECs and hDPSCs increased after co-culture with TNF-α (p < 0.05). TNF-α enhanced angiogenic ability in vitro in the co-culture system of hDPSCs and HUVECs.