Integrated multi-omics of the gastrointestinal microbiome and ruminant host reveals metabolic adaptation underlying early life development

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From Adversarial Arms Race to Model-centric Evaluation: Motivating a Unified Automatic Robustness Evaluation Framework

Textual adversarial attacks can discover models' weaknesses by adding semantic-preserved but misleading perturbations to the inputs. The long-lasting adversarial attack-and-defense arms race in Natural Language Processing (NLP) is algorithm-centric, providing valuable techniques for automatic robustness evaluation. However, the existing practice of robustness evaluation may exhibit issues of incomprehensive evaluation, impractical evaluation protocol, and invalid adversarial samples. In this paper, we aim to set up a unified automatic robustness evaluation framework, shifting towards model-centric evaluation to further exploit the advantages of adversarial attacks. To address the above challenges, we first determine robustness evaluation dimensions based on model capabilities and specify the reasonable algorithm to generate adversarial samples for each dimension. Then we establish the evaluation protocol, including evaluation settings and metrics, under realistic demands. Finally, we use the perturbation degree of adversarial samples to control the sample validity. We implement a toolkit RobTest that realizes our automatic robustness evaluation framework. In our experiments, we conduct a robustness evaluation of RoBERTa models to demonstrate the effectiveness of our evaluation framework, and further show the rationality of each component in the framework. The code will be made public at \url{https://github.com/thunlp/RobTest}.Comment: Accepted to Findings of ACL 202

Identification of novel urine proteomic biomarkers for high stamina in high-altitude adaptation

Introduction: We aimed to identify urine biomarkers for screening individuals with adaptability to high-altitude hypoxia with high stamina levels. Although most non-high-altitude natives experience rapid decline in physical ability when ascending to high altitudes, some individuals with high-altitude adaptability continue to maintain high endurance levels.Methods: We divided the study population into two groups: the LC group (low change in endurance from low to high altitude) and HC group (high change in endurance from low to high altitude). We performed blood biochemistry testing for individuals at high altitudes and sea level. We used urine peptidome profiling to compare the HH (high-altitude with high stamina) and HL (high-altitude with low stamina) groups and the LC and HC groups to identify urine biomarkers.Results: Routine blood tests revealed that the concentration of white blood cells, lymphocytes and platelets were significantly higher in the HH group than in the HL group. Urine peptidome profiling showed that the proteins ITIH1, PDCD1LG2, NME1-NME2, and CSPG4 were significantly differentially expressed between the HH and HL groups, which was tested using ELISA. Urine proteomic analysis showed that LRG1, NID1, VASN, GPX3, ACP2, and PRSS8 were urine proteomic biomarkers of high stamina during high-altitude adaptation.Conclusion: This study provides a novel approach for identifying potential biomarkers for screening individuals who can adapt to high altitudes with high stamina

The Long Noncoding RNA MALAT1 Induces Tolerogenic Dendritic Cells and Regulatory T Cells via miR155/Dendritic Cell-Specific Intercellular Adhesion Molecule-3 Grabbing Nonintegrin/IL10 Axis

By shaping T cell immunity, tolerogenic dendritic cells (tDCs) play critical roles in the induction of immune tolerance after transplantation. However, the role of long noncoding RNAs (lncRNAs) in the function and immune tolerance of dendritic cells (DCs) is largely unknown. Here, we found that the lncRNA MALAT1 is upregulated in the infiltrating cells of tolerized mice with cardiac allografts and activated DCs. Functionally, MALAT1 overexpression favored a switch in DCs toward a tolerant phenotype. Mechanistically, ectopic MALAT1 promoted dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN) expression by functioning as an miR155 sponge, which is essential for the tolerogenic maintenance of DCs and the DC-SIGN-positive subset with more potent tolerogenic ability. The adoptive transfer of MALAT1-overexpressing DCs promoted cardiac allograft survival and protected from the development of experimental autoimmune myocarditis, accompanied with increasing antigen-specific regulatory T cells. Therefore, overexpressed MALAT1 induces tDCs and immune tolerance in heart transplantation and autoimmune disease by the miRNA-155/DC-SIGH/IL10 axis. This study highlights that the lncRNA MALAT1 is a novel tolerance regulator in immunity that has important implications in settings in which tDCs are preferred

Field measurement of the erosion threshold of silty seabed in the intertidal flat of the Yellow River Delta with a newly-developed annular flume

Accurately measuring the critical shear stress is crucial for numerous applications, such as sediment transport modeling, erosion prediction, and the design of sustainable coastal engineering structures. However, developing reliable and precise in-situ measurement devices faces significant challenges due to the harsh and dynamic nature of aquatic environments. Factors like turbulence and waves introduce complexities that must be considered when designing and calibrating these devices. The newly developed Openable Underwater Carousel In-situ Flume (OUC-IF) was used to determine the critical shear stress (τc) and quantify erosion rates. Acoustic Doppler Velocimeter (ADV) was employed to measure 3D near-bottom velocities, which were then used to estimate and pre-calibrate bed shear stress (τ) applied on the seabed in the annular flume. Three computation methods of shear stress were evaluated: turbulent kinetic energy (TKE), direct covariance (COV), and log profile (LP). In-situ erosion experiments were conducted for the first time at two sites in the tidal flat of the Yellow River Delta (site 1 with a water depth of 1.32 m and site 2 with a water depth of 0.75 m). The critical shear stress was found to be 0.10 Pa at site 1 and 0.19 Pa at site 2, and the erosion rates of the sediments were successfully measured. The effect of wave-seabed interactions on erosion resistance was explored by theoretically estimating the wave-induced pore pressure of the seabed based on the observed data. The max liquefaction degree of the seabed at site 1 and site 2 was 0.035 and 0.057, respectively, and the average erosion coefficient Me was 2.63E-05 kg m-2s-1 at site 1 and 3.48E-05 kg m-2s-1 at site 2

Administration of Interleukin-35-Conditioned Autologous Tolerogenic Dendritic Cells Prolong Allograft Survival After Heart Transplantation

Background/Aims: IL-35, a powerful suppressor of inflammation and autoimmunity, is primarily secreted by regulatory T cells (Tregs) and can, in turn, promote Treg differentiation. However, the precise effect of IL-35 on dendritic cells (DCs) remains to be clarified. Methods: In this study, we investigated the expression of IL-35 in DCs after stimulation with LPS utilizing enzyme linked immunosorbent assay(ELISA), quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting, and the influence of IL-35 on the maturation and function of DCs by mixed lymphocyte reaction assay and flow cytometry. We further examined the regulation of IL-35 in DCs by the microRNA let-7i (let-7i) via transfected with let-7i mimic, inhibitor or suppressor of cytokine signalling 1 (SOCS1) siRNA. IL-35-overexpressing DCs were transfused into BALB/c recipients with C57BL/6 heart transplantations to verify the role of immune tolerance in transplantation. Results: The results showed that IL-35 expression was significantly up-regulated following lipopolysaccharide (LPS)-induced DC maturation. Overexpression of IL-35 suppressed DC maturation, promoted the secretion of anti-inflammatory cytokines, and subsequently affected the balance between Treg and Th17 cells. IL-35 expression in DCs was regulated by let-7i, which targets SOCS1. The transfusion of IL-35-transfected DCs induced Treg generation in mice and prolonged cardiac allograft survival. Conclusion: Our data demonstrated that IL-35 induces tolerogenic DCs which are capable of alleviating allograft rejection. Clinical application of IL-35-treated DCs might be a promising approach for eliciting cardiac allograft immune tolerance

Cyanidin-3-o-Glucoside Pharmacologically Inhibits Tumorigenesis via Estrogen Receptor β in Melanoma Mice

Expression patterns of estrogen receptors [ERα, ERβ, and G-protein associated ER (GPER)] in melanoma and skin may suggest their differential roles in carcinogenesis. Phytoestrogenic compound cyanidin-3-o-glucoside (C3G) has been shown to inhibit the growth and metastatic potential of melanoma, although the underlying molecular mechanism remains unclear. The aim of this study was to clarify the mechanism of action of C3G in melanoma in vitro and in vivo, as well as to characterize the functional expressions of ERs in melanoma. In normal skin or melanoma (n = 20/each), no ERα protein was detectable, whereas expression of ERβ was high in skin but weak focal or negative in melanoma; and finally high expression of GPER in all skin vs. 50% melanoma tissues (10/20) was found. These results correspond with our analysis of the melanoma survival rates (SRs) from Human Protein Atlas and The Cancer Genome Atlas GDC (362 patients), where low ERβ expression in melanoma correlate with a poor relapse-free survival, and no correlations were observed between SRs and ERα or GPER expression in melanoma. Furthermore, we demonstrated that C3G treatment arrested the cell cycle at the G2/M phase by targeting cyclin B1 (CCNB1) and promoted apoptosis via ERβ in both mouse and human melanoma cell lines, and inhibited melanoma cell growth in vivo. Our study suggested that C3G elicits an agonistic effect toward ERβ signaling enhancement, which may serve as a potential novel therapeutic and preventive approach for melanoma

Impacts of Consolidation Time on the Critical Hydraulic Gradient of Newly Deposited Silty Seabed in the Yellow River Delta

The silty seabed in the Yellow River Delta (YRD) is exposed to deposition, liquefaction, and reconsolidation repeatedly, during which seepage flows are crucial to the seabed strength. In extreme cases, seepage flows could cause seepage failure (SF) in the seabed, endangering the offshore structures. A critical condition exists for the occurrence of SF, i.e., the critical hydraulic gradient (icr). Compared with cohesionless sands, the icr of cohesive sediments is more complex, and no universal evaluation theory is available yet. The present work first improved a self-designed annular flume to avoid SF along the sidewall, then simulated the SF process of the seabed with different consolidation times in order to explore the icr of newly deposited silty seabed in the YRD. It is found that the theoretical formula for icr of cohesionless soil grossly underestimated the icr of cohesive soil. The icr range of silty seabed in the YRD was 8–16, which was significantly affected by the cohesion and was inversely proportional to the seabed fluidization degree. SF could “pump” the sediments vertically from the interior of the seabed with a contribution to sediment resuspension of up to 93.2–96.8%. The higher the consolidation degree, the smaller the contribution will be