Cell death and immune response are at the core of life. In past decades, the endoplasmic reticulum (ER) protein STING1 (also known as STING or TMEM173) was found to play a fundamental role in the ...production of type I interferons (IFNs) and pro-inflammatory cytokines in response to DNA derived from invading microbial pathogens or damaged hosts by activating multiple transcription factors. In addition to this well-known function in infection, inflammation, and immunity, emerging evidence suggests that the STING1-dependent signaling network is implicated in health and disease by regulating autophagic degradation or various cell death modalities (e.g., apoptosis, necroptosis, pyroptosis, ferroptosis, mitotic cell death, and immunogenic cell death ICD). Here, we outline the latest advances in our understanding of the regulating mechanisms and signaling pathways of STING1 in autophagy and cell death, which may shed light on new targets for therapeutic interventions.
A quantum anomalous Hall (QAH) insulator coupled to an s-wave superconductor is predicted to harbor chiral Majorana modes. A recent experiment interprets the half-quantized two-terminal conductance ...plateau as evidence for these modes in a millimeter-size QAH-niobium hybrid device. However, non-Majorana mechanisms can also generate similar signatures, especially in disordered samples. Here, we studied similar hybrid devices with a well-controlled and transparent interface between the superconductor and the QAH insulator. When the devices are in the QAH state with well-aligned magnetization, the two-terminal conductance is always half-quantized. Our experiment provides a comprehensive understanding of the superconducting proximity effect observed in QAH-superconductor hybrid devices and shows that the half-quantized conductance plateau is unlikely to be induced by chiral Majorana fermions in samples with a highly transparent interface.
Inter-site interaction in densely populated single-atom catalysts has been demonstrated to have a crucial role in regulating the electronic structure of metal atoms, and consequently their catalytic ...performances. We herein report a general and facile strategy for the synthesis of several densely populated single-atom catalysts. Taking cobalt as an example, we further produce a series of Co single-atom catalysts with varying loadings to investigate the influence of density on regulating the electronic structure and catalytic performance in alkene epoxidation with O
. Interestingly, the turnover frequency and mass-specific activity are significantly enhanced by 10 times and 30 times with increasing Co loading from 5.4 wt% to 21.2 wt% in trans-stilbene epoxidation, respectively. Further theoretical studies reveal that the electronic structure of densely populated Co atoms is altered through charge redistribution, resulting in less Bader charger and higher d-band center, which are demonstrated to be more beneficial for the activation of O
and trans-stilbene. The present study demonstrates a new finding about the site interaction in densely populated single-atom catalysts, shedding insight on how density affects the electronic structure and catalytic performance for alkene epoxidation.
The Bloom’s helicase ortholog, Sgs1, plays central roles to coordinate the formation and resolution of joint molecule intermediates (JMs) during meiotic recombination in budding yeast. Sgs1 can ...associate with type-I topoisomerase Top3 and its accessory factor Rmi1 to form a conserved complex best known for its unique ability to decatenate double-Holliday junctions. Contrary to expectations, we show that the strand-passage activity of Top3-Rmi1 is required for all known functions of Sgs1 in meiotic recombination, including channeling JMs into physiological crossover and noncrossover pathways, and suppression of non-allelic recombination. We infer that Sgs1 always functions in the context of the Sgs1-Top3-Rmi1 complex to regulate meiotic recombination. In addition, we reveal a distinct late role for Top3-Rmi1 in resolving recombination-dependent chromosome entanglements to allow segregation at anaphase. Surprisingly, Sgs1 does not share this essential role of Top3-Rmi1. These data reveal an essential and pervasive role for the Top3-Rmi1 decatenase during meiosis.
Display omitted
•DNA strand passage by Top3-Rmi1 is pivotal for meiotic recombination•Conditional alleles define temporally and functionally distinct roles of Top3-Rmi1•Top3-Rmi1 partners with RecQ helicase BLM/Sgs1 to prevent abnormal recombination•Top3-Rmi1 is essential for disentangling chromosomes enabling complete separation
Topoisomerases are essential for chromosome metabolism. Tang et al. show that the Top3-Rmi1 complex must decatenate DNA strands to process intermediates during homologous recombination. Top3-Rmi1 partners with BLM/Sgs1 to prevent abnormal recombination. Top3-Rmi1 is also essential for disentangling chromosomes, enabling their complete separation.
Because it is difficulty to classify level of fabric wrinkle, this paper proposes a fabric winkle level classification model via online sequential extreme learning machine based on improved sine ...cosine algorithm (SCA). The SCA has excellent global optimization ability, can explore different search spaces, and effectively avoid falling into local optimum. Because the initial population of SCA will have an impact on its optimization speed and quality, the SCA is initialized by differential evolution (DE) to avoid local optimization, and then the output weight and hidden layer bias are optimized; that is, the improved SCA is used to select the optimal parameters of the online sequential extreme learning machine (OSELM) to improve the generalization performance of the algorithm. To verify the performance of the proposed model DE-SCA-OSELM, it will be compared with other algorithms using a fabric wrinkles dataset collected under standard conditions. The experimental results indicate that the proposed model can effectively find the optimal parameter value of OSELM. The average classification accuracy increased by 6.95%, 3.62%, 6.67%, and 3.34%, respectively, compared with the partial algorithms OSELM, SCAELM, RVFL and PSOSVM, which meets expectations.
Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare clinical syndrome with a high mortality rate. There is no biomarker to predict the early therapeutic response.
Objective: Our study ...explores the significance of serum ferritin in predicting the response of induction therapy.
Methods: We retrospectively analyzed the clinical data of 102 adult patients with HLH admitted to our hospital. These patients received HLH-94 regimen for induction therapy. The patients were divided into remission group and non-remission group according to the response of induction therapy.
Results: Ferritin values between 1-4 weeks post induction were predictive of remission (p<.05), which were higher in the non-remission group than in the remission group. Ferritin obtained 2 weeks post-induction had the highest ROC for predicting remission, with a cut-off value of 1188.5 µg/L. And patients with ferritin lower than 1188.5 µg/L had better response of induction therapy.
Conclusion: Our study suggests that serum ferritin is a good indicator to predict the efficacy of induction therapy for adult HLH.
KEY MESSAGES
Serum ferritin is a good indicator for predicting the efficacy of adult HLH induction therapy.
Serum ferritin two weeks after treatment may be a better indicator to judge the early curative effect.
Serum ferritin after treatment also had a predictive significance for the survival of HLH.
Street vitality plays an important role in improving residents’ quality of life and advancing urban development. However, traditional research methods pay minimal attention to pedestrians’ behavior, ...ignoring crowd preferences vis-à-vis the street-space. Utilizing the historic block of Shapowei in Xiamen as an illustrative example, this manuscript systematically examines the impact of this historic block’s built environment on street vitality. Using multimode analysis technologies including Global Positioning System (GPS) and Geographic Information System (GIS) software helps analyze time and space data on pedestrians; evaluates the space perception of the residents; assesses the street’s visual appeal, as well as the appeal of its commercial activities; identifies the environmental elements and rules of the high-vitality street space. Therefore, it puts forward suggestions for street planning and architectural design. This article constructs a street vitality evaluation system based on pedestrians’ time and space data, providing a new perspective for the research and design of the historical block space. In conclusion, the research suggests that the spatial change of the street, the openness of the building facade, and the spatial distribution of the shops have different impacts on pedestrians’ activities when the built-up environment is a concern.
Nonlinear Hall effect (NLHE) is a new type of Hall effect with wide application prospects. Practical device applications require strong NLHE at room temperature (RT). However, previously reported ...NLHEs are all low-temperature phenomena except for the surface NLHE of TaIrTe
. Bulk RT NLHE is highly desired due to its ability to generate large photocurrent. Here, we show the spin-valley locked Dirac state in BaMnSb
can generate a strong bulk NLHE at RT. In the microscale devices, we observe the typical signature of an intrinsic NLHE, i.e. the transverse Hall voltage quadratically scales with the longitudinal current as the current is applied to the Berry curvature dipole direction. Furthermore, we also demonstrate our nonlinear Hall device's functionality in wireless microwave detection and frequency doubling. These findings broaden the coupled spin and valley physics from 2D systems into a 3D system and lay a foundation for exploring bulk NLHE's applications.
Stimulator of interferon response cGAMP interactor 1 (STING1), also known as TMEM173, is an immune adaptor protein that governs signal crosstalk that is implicated in many physiological and ...pathological processes. Although it has been established that STING1 traffics from the endoplasmic reticulum (ER) to Golgi apparatus (Golgi) upon DNA-triggered activation, emerging evidence reveals that STING1 can be transported to different organelles, which dictate its immune-dependent (e.g., the production of type I interferons and pro-inflammatory cytokines) and -independent (e.g., the activation of autophagy and cell death) functions. In this brief review, we outline the roles of STING1 in different organelles (including the ER, ER-Golgi intermediate compartment, Golgi, mitochondria, endosomes, lysosomes, and nucleus) and discuss the potential relevance of these roles to diseases and pharmacological interventions.
•Metabolomics for distinguishing live from dead pork meat was firstly developed.•Untargeted and pseudotargeted metabolomics determined 14 differential markers.•Some differential markers were ...identified as carnosine, l-carnitine, l-histidine.•Approach was accurate in quantification to exclude the false-positive metabolites.•Developed approach would be applied to evaluate the quality and safety of foods.
An untargeted and pseudotargeted metabolomic combination approach was developed to identify reliable and stable differential markers which can distinguish between pork meat from live pigs conventionally butchered and pork meat from dead pigs butchered immediately after death from diseases or other abnormalities. In this study, 24 differential metabolites of interest were screened by the UHPLC–Triple–TOF–MS-based untargeted metabolomic method, and 14 differential markers were detected by the UHPLC–QTRAP–MS-based pseudotargeted metabolomic method after performing statistical analysis to remove false-positive differential metabolites. Among the possible differential markers identified using the Metlin database and references were carnosine, l-carnitine, l-histidine, N-acetylhistidine, acetylcholine, l-acetylcarnitine and two phosphatidylcholines. The results of the principal component analysis (PCA) and the hierarchical clustering analysis (HCA) indicate that 14 differential markers could be potentially used to distinguish live and dead pork meat. This reliable and stable approach not only could detect the unknown differential markers, but also accurately quantify them.
PDF
