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Federated Learning is an effective solution to address the issues of data isolation and privacy leakage in machine learning. However, ensuring the security of network devices and architectures deploying federated learning remains a challenge due to network attacks. This paper proposes an attention-based Graph Neural Network for detecting cross-level and cross-department network attacks. This method enables collaborative model training while protecting data privacy on distributed devices. By organizing network traffic information in chronological order and constructing a graph structure based on log density, enhances the accuracy of network attack detection. The introduction of an attention mechanism and the construction of a Federated Graph Attention Network (FedGAT) model are used to evaluate the interactivity between nodes in the graph, thereby improving the precision of internal network interactions. Experimental results demonstrate that our method achieves comparable accuracy and robustness to traditional detection methods while prioritizing privacy protection and data security.

A cryo-EM structure of the human 26S proteasome in a resting state at an average resolution of 3.5 Å reveals details in the interactions between subunits. An additional structure of the proteasome with USP14 bound suggests a mechanism for its activation. We report the cryo-EM structure of the human 26S proteasome at an average resolution of 3.5 Å, allowing atomic modeling of 28 subunits in the core particle (CP) and 18 subunits in the regulatory particle (RP). The C-terminal residues of Rpt3 and Rpt5 subunits in the RP can be seen inserted into surface pockets formed between adjacent α subunits in the CP. Each of the six Rpt subunits contains a bound nucleotide, and the central gate of the CP α-ring is closed despite RP association. The six pore 1 loops in the Rpt ring are arranged similarly to a spiral staircase along the axial channel of substrate transport, which is constricted by the pore 2 loops. We also determined the cryo-EM structure of the human proteasome bound to the deubiquitinating enzyme USP14 at 4.35-Å resolution. Together, our structures provide a framework for mechanistic understanding of eukaryotic proteasome function.

Currently, chemotherapy is the main treatment for tumors, but there are still problems such as unsatisfactory chemotherapy results, susceptibility to drug resistance, and serious adverse effects. Natural compounds have numerous pharmacological activities which are important sources of drug discovery for tumor treatment. The combination of chemotherapeutic drugs and natural compounds is gradually becoming an important strategy and development direction for tumor treatment. In this paper, we described the role of natural compounds in combination with chemotherapeutic drugs in synergizing, reducing drug resistance, mitigating adverse effects and related mechanisms, and providing new insights for future oncology research.

There is growing interest in using functional foods or nutraceuticals for the prevention and treatment of hypertension or high blood pressure. Although numerous preventive and therapeutic pharmacological interventions are available on the market, unfortunately, many patients still suffer from poorly controlled hypertension. Furthermore, most pharmacological drugs, such as inhibitors of angiotensin-I converting enzyme (ACE), are often associated with significant adverse effects. Many bioactive food compounds have been characterized over the past decades that may contribute to the management of hypertension; for example, bioactive peptides derived from various food proteins with antihypertensive properties have gained a great deal of attention. Some of these peptides have exhibited potent in vivo antihypertensive activity in both animal models and human clinical trials. This review provides an overview about the complex pathophysiology of hypertension and demonstrates the potential roles of food derived bioactive peptides as viable interventions targeting specific pathways involved in this disease process. This review offers a comprehensive guide for understanding and utilizing the molecular mechanisms of antihypertensive actions of food protein derived peptides.

Voltage-gated sodium (Na v ) channels respond to a change in voltage potential by allowing sodium ions to move into cells, thus initiating electrical signaling. Mutations in Na v channels cause neurological and cardiovascular disorders, making the channels important therapeutic targets. Shen et al. determined a high-resolution structure of a Na v channel from the American cockroach by electron microscopy. The structure affords insight into voltage sensing and ion permeability and provides a foundation for understanding function and disease mechanism of Na v and the related Ca v ion channels. Science , this issue p. eaal4326 The cryo–electron microscopy structure of a cockroach sodium channel provides a foundation for understanding the channel’s function and disease mechanism. Voltage-gated sodium (Na v ) channels are responsible for the initiation and propagation of action potentials. They are associated with a variety of channelopathies and are targeted by multiple pharmaceutical drugs and natural toxins. Here, we report the cryogenic electron microscopy structure of a putative Na v channel from American cockroach (designated Na v PaS) at 3.8 angstrom resolution. The voltage-sensing domains (VSDs) of the four repeats exhibit distinct conformations. The entrance to the asymmetric selectivity filter vestibule is guarded by heavily glycosylated and disulfide bond–stabilized extracellular loops. On the cytoplasmic side, a conserved amino-terminal domain is placed below VSD I , and a carboxy-terminal domain binds to the III-IV linker. The structure of Na v PaS establishes an important foundation for understanding function and disease mechanism of Na v and related voltage-gated calcium channels.

The cation channel of sperm (CatSper) is essential for sperm motility and fertility 1 , 2 . CatSper comprises the pore-forming proteins CATSPER1–4 and multiple auxiliary subunits, including CATSPERβ, γ, δ, ε, ζ, and EFCAB9 1 , 3 – 9 . Here we report the cryo-electron microscopy (cryo-EM) structure of the CatSper complex isolated from mouse sperm. In the extracellular view, CATSPER1–4 conform to the conventional domain-swapped voltage-gated ion channel fold 10 , following a counterclockwise arrangement. The auxiliary subunits CATSPERβ, γ, δ and ε—each of which contains a single transmembrane segment and a large extracellular domain—constitute a pavilion-like structure that stabilizes the entire complex through interactions with CATSPER4, 1, 3 and 2, respectively. Our EM map reveals several previously uncharacterized components, exemplified by the organic anion transporter SLCO6C1. We name this channel–transporter ultracomplex the CatSpermasome. The assembly and organization details of the CatSpermasome presented here lay the foundation for the development of CatSpermasome-related treatments for male infertility and non-hormonal contraceptives. A structure of the sperm-specific CatSper complex features a number of additional components; together, these components and the CatSper complex are termed the CatSpermasome.

Chronic diseases such as atherosclerosis and cancer are now the leading causes of morbidity and mortality worldwide. Inflammatory processes and oxidative stress underlie the pathogenesis of these pathological conditions. Bioactive peptides derived from food proteins have been evaluated for various beneficial effects, including anti-inflammatory and antioxidant properties. In this review, we summarize the roles of various food-derived bioactive peptides in inflammation and oxidative stress and discuss the potential benefits and limitations of using these compounds against the burden of chronic diseases.

The glucose transporter GLUT1 catalyses facilitative diffusion of glucose into erythrocytes and is responsible for glucose supply to the brain and other organs. Dysfunctional mutations may lead to GLUT1 deficiency syndrome, whereas overexpression of GLUT1 is a prognostic indicator for cancer. Despite decades of investigation, the structure of GLUT1 remains unknown. Here we report the crystal structure of human GLUT1 at 3.2 Å resolution. The full-length protein, which has a canonical major facilitator superfamily fold, is captured in an inward-open conformation. This structure allows accurate mapping and potential mechanistic interpretation of disease-associated mutations in GLUT1. Structure-based analysis of these mutations provides an insight into the alternating access mechanism of GLUT1 and other members of the sugar porter subfamily. Structural comparison of the uniporter GLUT1 with its bacterial homologue XylE, a proton-coupled xylose symporter, allows examination of the transport mechanisms of both passive facilitators and active transporters. The structure of human GLUT1 in an inward-open conformation is reported; access to the structure of the human protein, instead of just a bacterial homologue, made it possible to map (inactivating) mutations associated with GLUT1 deficiency syndrome onto the structure. Human GLUT1 glucose transporter structure GLUT1 is a membrane protein that is responsible for the uptake of glucose into erythrocytes and other cells. The structure of a proton-coupled xylose symporter that is a bacterial homologue of GLUT1 has been reported previously and here Nieng Yan and colleagues report the structure of human GLUT1 in an inward-open conformation. Having access to the structure of the human protein, the authors were able to map inactivating mutations associated with GLUT1 deficiency syndrome — also known as De Vivo syndrome — onto their structure. Because elevated expression levels of GLUT1 have been observed in several cancer types, access to this structure may facilitate the development of new anticancer agents.

The nighttime light (NTL) satellite data have been widely used to investigate the urbanization process. The Defense Meteorological Satellite Program Operational Linescan System (DMSP-OLS) stable nighttime light data and Suomi National Polar-orbiting Partnership Visible Infrared Imaging Radiometer Suite (NPP-VIIRS) nighttime light data are two widely used NTL datasets. However, the difference in their spatial resolutions and sensor design requires a cross-sensor calibration of these two datasets for analyzing a long-term urbanization process. Different from the traditional cross-sensor calibration of NTL data by converting NPP-VIIRS to DMSP-OLS-like NTL data, this study built an extended time series (2000–2018) of NPP-VIIRS-like NTL data through a new cross-sensor calibration from DMSP-OLS NTL data (2000–2012) and a composition of monthly NPP-VIIRS NTL data (2013–2018). The proposed cross-sensor calibration is unique due to the image enhancement by using a vegetation index and an auto-encoder model. Compared with the annual composited NPP-VIIRS NTL data in 2012, our product of extended NPP-VIIRS-like NTL data shows a good consistency at the pixel and city levels with R2 of 0.87 and 0.95, respectively. We also found that our product has great accuracy by comparing it with DMSP-OLS radiance-calibrated NTL (RNTL) data in 2000, 2004, 2006, and 2010. Generally, our extended NPP-VIIRS-like NTL data (2000–2018) have an excellent spatial pattern and temporal consistency which are similar to the composited NPP-VIIRS NTL data. In addition, the resulting product could be easily updated and provide a useful proxy to monitor the dynamics of demographic and socioeconomic activities for a longer time period compared to existing products. The extended time series (2000–2018) of nighttime light data is freely accessible at https://doi.org/10.7910/DVN/YGIVCD (Chen et al., 2020).

Milk derived tripeptides IPP (Ile-Pro-Pro) and VPP (Val-Pro-Pro) have shown promise as anti-hypertensive agents due to their inhibitory effects on angiotensin converting enzyme (ACE). Due to the key inter-related roles of hypertension, chronic inflammation and insulin resistance in the pathogenesis of metabolic syndrome, there is growing interest in investigating established anti-hypertensive agents for their effects on insulin sensitivity and inflammation. In this study, we examined the effects of IPP and VPP on 3T3-F442A murine pre-adipocytes, a widely used model for studying metabolic diseases. We found that both IPP and VPP induced beneficial adipogenic differentiation as manifested by intracellular lipid accumulation, upregulation of peroxisome proliferator-activated receptor gamma (PPARγ) and secretion of the protective lipid hormone adiponectin by these cells. The observed effects were similar to those induced by insulin, suggesting potential benefits in the presence of insulin resistance. IPP and VPP also inhibited cytokine induced pro-inflammatory changes such as reduction in adipokine levels and activation of the nuclear factor kappa B (NF-κB) pathway. Taken together, our findings suggest that IPP and VPP exert insulin-mimetic adipogenic effects and prevent inflammatory changes in adipocytes, which may offer protection against metabolic disease.