Integrated multi-omics identified the novel intratumor microbiome-derived subtypes and signature to predict the outcome, tumor microenvironment heterogeneity, and immunotherapy response for pancreatic cancer patients

Background: The extremely malignant tumour known as pancreatic cancer (PC) lacks efficient prognostic markers and treatment strategies. The microbiome is crucial to how cancer develops and responds to treatment. Our study was conducted in order to better understand how PC patients’ microbiomes influence their outcome, tumour microenvironment, and responsiveness to immunotherapy.Methods: We integrated transcriptome and microbiome data of PC and used univariable Cox regression and Kaplan–Meier method for screening the prognostic microbes. Then intratumor microbiome-derived subtypes were identified using consensus clustering. We utilized LASSO and Cox regression to build the microbe-related model for predicting the prognosis of PC, and utilized eight algorithms to assess the immune microenvironment feature. The OncoPredict package was utilized to predict drug treatment response. We utilized qRT-PCR to verify gene expression and single-cell analysis to reveal the composition of PC tumour microenvironment.Results: We obtained a total of 26 prognostic genera in PC. And PC samples were divided into two microbiome-related subtypes: Mcluster A and B. Compared with Mcluster A, patients in Mcluster B had a worse prognosis and higher TNM stage and pathological grade. Immune analysis revealed that neutrophils, regulatory T cell, CD8+ T cell, macrophages M1 and M2, cancer associated fibroblasts, myeloid dendritic cell, and activated mast cell had remarkably higher infiltrated levels within the tumour microenvironment of Mcluster B. Patients in Mcluster A were more likely to benefit from CTLA-4 blockers and were highly sensitive to 5-fluorouracil, cisplatin, gemcitabine, irinotecan, oxaliplatin, and epirubicin. Moreover, we built a microbe-derived model to assess the outcome. The ROC curves showed that the microbe-related model has good predictive performance. The expression of LAMA3 and LIPH was markedly increased within pancreatic tumour tissues and was linked to advanced stage and poor prognosis. Single-cell analysis indicated that besides cancer cells, the tumour microenvironment of PC was also rich in monocytes/macrophages, endothelial cells, and fibroblasts. LIPH and LAMA3 exhibited relatively higher expression in cancer cells and neutrophils.Conclusion: The intratumor microbiome-derived subtypes and signature in PC were first established, and our study provided novel perspectives on PC prognostic indicators and treatment options

Chiral symmetry breaking for deterministic switching of perpendicular magnetization by spin-orbit torque

Symmetry breaking is a characteristic to determine which branch of a bifurcation system follows upon crossing a critical point. Specifically, in spin-orbit torque (SOT) devices, a fundamental question arises: how to break the symmetry of the perpendicular magnetic moment by the in-plane spin polarization? Here, we show that the chiral symmetry breaking by the DMI can induce the deterministic SOT switching of the perpendicular magnetization. By introducing a gradient of saturation magnetization or magnetic anisotropy, non-collinear spin textures are formed by the gradient of effective SOT strength, and thus the chiral symmetry of the SOT-induced spin textures is broken by the DMI, resulting in the deterministic magnetization switching. We introduce a strategy to induce an out-of-plane (z) gradient of magnetic properties, as a practical solution for the wafer-scale manufacture of SOT devices.Comment: 16 pages, 4 figure

Analysis of the response regulatory network of pepper genes under hydrogen peroxide stress

Hydrogen peroxide (H2O2) is a regulatory component related to plant signal transduction. To better understand the genome-wide gene expression response to H2O2 stress in pepper plants, a regulatory network of H2O2 stress-gene expression in pepper leaves and roots was constructed in the present study. We collected the normal tissues of leaves and roots of pepper plants after 40 days of H2O2 treatment and obtained the RNA-seq data of leaves and roots exposed to H2O2 for 0.5–24 h. By comparing the gene responses of pepper leaves and roots exposed to H2O2 stress for different time periods, we found that the response in roots reached the peak at 3 h, whereas the response in leaves reached the peak at 24 h after treatment, and the response degree in the roots was higher than that in the leaves. We used all datasets for K-means analysis and network analysis identified the clusters related to stress response and related genes. In addition, CaEBS1, CaRAP2, and CabHLH029 were identified through a co-expression analysis and were found to be strongly related to several reactive oxygen species-scavenging enzyme genes; their homologous genes in Arabidopsis showed important functions in response to hypoxia or iron uptake. This study provides a theoretical basis for determining the dynamic response process of pepper plants to H2O2 stress in leaves and roots, as well as for determining the critical time and the molecular mechanism of H2O2 stress response in leaves and roots. The candidate transcription factors identified in this study can be used as a reference for further experimental verification

Extreme long-lifetime self-assembled monolayer for air-stable molecular junctions

The molecular electronic devices based on self-assembled monolayer (SAM) on metal surfaces demonstrate novel electronic functions for device minimization yet are unable to realize in practical applications, due to their instability against oxidation of the sulfur-metal bond. This paper describes an alternative to the thiolate anchoring group to form stable SAMs on gold by selenides anchoring group. Because of the formation of strong selenium-gold bonds, these stable SAMs allow us to incorporate them in molecular tunnel junctions to yield extremely stable junctions for over 200 days. A detailed structural characterization supported by spectroscopy and first-principles modeling shows that the oxidation process is much slower with the selenium-gold bond than the sulfur-gold bond, and the selenium-gold bond is strong enough to avoid bond breaking even when it is eventually oxidized. This proof of concept demonstrates that the extraordinarily stable SAMs derived from sel-enides are useful for long-lived molecular electronic devices and can possibly become important in many air-stable applications involving SAMs.</p

Plant-Morphing Strategies and Plant-Inspired Soft Actuators Fabricated by Biomimetic Four-Dimensional Printing: A Review

From Frontiers via Jisc Publications RouterHistory: collection 2021, received 2021-01-10, accepted 2021-03-09, epub 2021-05-04Publication status: PublishedFor prey, seeding, and protection, plants exhibit ingenious adaptive motions that respond autonomously to environmental stimuli by varying cellular organization, anisotropic orientation of cellulose fibers, mechanical instability design, etc. Notably, plants do not leverage muscle and nerves to produce and regulate their motions. In contrast, they harvest energy from the ambient environment and compute through embodied intelligence. These characteristics make them ideal candidates for application in self-morphing devices. Four-dimensional (4D) printing is a bottom-up additive manufacturing method that builds objects with the ability to change shape/properties in a predetermined manner. A versatile motion design catalog is required to predict the morphing processes and final states of the printed parts. This review summarizes the morphing and actuation mechanisms of plants and concludes with the recent development of 4D-printed smart materials inspired by the locomotion and structures of plant systems. We provide analyses of the challenges and our visions of biomimetic 4D printing, hoping to boost its application in soft robotics, smart medical devices, smart parts in aerospace, etc

Tunable van Hove singularity without structural instability in Kagome metal CsTi3_3Bi5_5

In Kagome metal CsV$_3$Sb$_5$, multiple intertwined orders are accompanied by both electronic and structural instabilities. These exotic orders have attracted much recent attention, but their origins remain elusive. The newly discovered CsTi$_3$Bi$_5$ is a Ti-based Kagome metal to parallel CsV$_3$Sb$_5$. Here, we report angle-resolved photoemission experiments and first-principles calculations on pristine and Cs-doped CsTi$_3$Bi$_5$ samples. Our results reveal that the van Hove singularity (vHS) in CsTi$_3$Bi$_5$ can be tuned in a large energy range without structural instability, different from that in CsV$_3$Sb$_5$. As such, CsTi$_3$Bi$_5$ provides a complementary platform to disentangle and investigate the electronic instability with a tunable vHS in Kagome metals

Genome-Wide Identification and Capsaicinoid Biosynthesis-Related Expression Analysis of the R2R3-MYB Gene Family in Capsicum annuum L.

Capsaicinoids are naturally specialized metabolites in pepper and are the main reason that Capsicum fruits have a pungent smell. During the synthesis of capsaicin, MYB transcription factors play key regulatory roles. In particular, R2R3-MYB subfamily genes are the most important members of the MYB family and are critical candidate factors in capsaicinoid biosynthesis. The 108 R2R3-MYB genes in pepper were identified in this study and all are shown to have two highly conserved MYB binding domains. Phylogenetic and structural analyses clustered CaR2R3-MYB genes into seven groups. Interspecies collinearity analysis found that the R2R3-MYB family contains 16 duplicated gene pairs and the highest gene density is on chromosome 00 and 03. The expression levels of CaR2R3-MYB differentially expressed genes (DEGs) and capsaicinoid-biosynthetic genes (CBGs) in fruit development stages were obtained via RNA-seq and quantitative polymerase chain reaction (qRT-PCR). Co-expression analyses reveal that highly expressed CaR2R3-MYB genes are co-expressed with CBGs during early stages of pericarp and placenta development processes. It is speculated that six candidate CaR2R3-MYB genes are involved in regulating the synthesis of capsaicin and dihydrocapsaicin. This study is the first systematic analysis of the CaR2R3-MYB gene family and provided references for studying their molecular functions. At the same time, these results also laid the foundation for further research on the capsaicin characteristics of CaR2R3-MYB genes in pepper

The relationship between daytime napping and glycemic control in people with type 2 diabetes

AimTo examine the association between napping characteristics and glycemic control in people with type 2 diabetes.DesignThis study used a cross-sectional design.MethodsA convenience sample of people with type 2 diabetes (N=226) were included. Glycemic control was indicated by HbA1c which was measured by A1C Now®+. Napping characteristics including napping frequency, duration, timing, and type were measured by validated questionnaires. Other variables, such as insomnia, cognitive impairment, and depression were measured by the Insomnia Severity Index, Montreal Cognitive Assessment, and Patient Health Questionnaire-9, respectively. Multivariate linear regression analyses were performed.ResultsThe sample consisted of 122 women (54.0%), with a median age of 67 years. Their median HbA1c was 6.8%. No significant relationship was found between napping frequency and HbA1c. Among nappers, after controlling for covariates, long napping duration (≥60 min) and morning napping were both associated with poorer glycemic control. Compared with appetitive napping, restorative napping was associated with better glycemic control.ConclusionDaytime napping (e.g., duration and type) is an important modifiable factor for glycemic control in people with type 2 diabetes. This study provides new insights into the relationship between napping and glucose management among people with diabetes