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For high‐energy lithium–sulfur batteries, the poor volumetric energy density is a bottleneck as compared with lithium–ion batteries, due to the low density of both the sulfur active material and sulfur host. Herein, in order to enhance the volumetric energy density of sulfur cathode, a universal approach is proposed to fabricate a compact sulfur cathode with dense materials as sulfur host, instead of the old‐fashioned lightweight carbon nanomaterials. Based on this strategy, heavy lanthanum strontium manganese oxide (La0.8Sr0.2MnO3), with a high theoretical density of up to 6.5 g cm−3, is introduced as sulfur host. Meanwhile, the La0.8Sr0.2MnO3 host also acts as an efficient electrocatalyst to accelerate the diffusion, adsorption, and redox dynamics of lithium polysulfides in the charge–discharge processes. As a result, such S/La0.8Sr0.2MnO3 cathode presents high gravimetric/volumetric capacity and outstanding cycling stability. Moreover, an ultra‐high volumetric energy density of 2727 Wh L−1‐cathode is achieved based on the densification effect with higher density (1.69 g cm−3), which is competitive to the Ni‐rich oxide cathode (1800–2160 Wh L−1) of lithium–ion batteries. The current study opens up a path for constructing high volumetric capacity sulfur cathode with heavy and catalytic host toward practical applications of lithium–sulfur batteries. Heavy metal oxides are more suitable than light carbon materials to fabricate compact cathode for lithium–sulfur batteries. Specifically, lanthanum strontium manganese oxide nanofibers, with the tap density of 2.59 g cm−3, display efficient catalytic activity toward lithium polysulfides, enhancing the volumetric energy density of sulfur cathode, which can even exceed lithium–ion batteries.

Plant development and pattern formation depend on diffusible signals and location cues. These developmental signals and cues activate intracellular downstream components through cell surface receptors that direct cells to adopt specific fates for optimal function and establish biological fitness. There may be a single-pole dual-control competing mode in controlling plant development and microbial infection. In plant development, paracrine signaling molecules compete with autocrine signaling molecules to bind receptors or receptor complexes, turn on antagonistic molecular mechanisms, and precisely regulate developmental processes. In the process of microbial infection, two different signaling molecules, competing receptors or receptor complexes, form their respective signaling complexes, trigger opposite signaling pathways, establish symbiosis or immunity, and achieve biological adaptation. We reviewed several “single-pole dual-control” competing modes, focusing on analyzing the competitive commonality and characterization of “single-pole dual-control” molecular mechanisms. We suggest it might be an economical protective mechanism for plants’ sequentially and iteratively programmed developmental events. This mechanism may also be a paradigm for reducing internal friction in the struggle and coexistence with microbes. It provides extraordinary insights into molecular recognition, cell-to-cell communication, and protein–protein interactions. A detailed understanding of the “single-pole dual-control” competing mode will contribute to the discovery of more receptors or antagonistic peptides, and lay the foundation for food, biofuel production, and crop improvement.

Background Studies on the relationship between insulin resistance (IR) surrogates and long-term all-cause mortality in patients with coronary heart disease (CHD) and hypertension are lacking. This study aimed to explore the relationship between different IR surrogates and all-cause mortality and identify valuable predictors of survival status in this population. Methods The data came from the National Health and Nutrition Examination Survey (NHANES 2001–2018) and National Death Index (NDI). Multivariate Cox regression and restricted cubic splines (RCS) were performed to evaluate the relationship between homeostatic model assessment of IR (HOMA-IR), triglyceride glucose index (TyG index), triglyceride glucose-body mass index (TyG-BMI index) and all-cause mortality. The recursive algorithm was conducted to calculate inflection points when segmenting effects were found. Then, segmented Kaplan–Meier analysis, LogRank tests, and multivariable Cox regression were carried out. Receiver operating characteristic (ROC) and calibration curves were drawn to evaluate the differentiation and accuracy of IR surrogates in predicting the all-cause mortality. Stratified analysis and interaction tests were conducted according to age, gender, diabetes, cancer, hypoglycemic and lipid-lowering drug use. Results 1126 participants were included in the study. During the median follow-up of 76 months, 455 participants died. RCS showed that HOMA-IR had a segmented effect on all-cause mortality. 3.59 was a statistically significant inflection point. When the HOMA-IR was less than 3.59, it was negatively associated with all-cause mortality [HR = 0.87,95%CI (0.78, 0.97)]. Conversely, when the HOMA-IR was greater than 3.59, it was positively associated with all-cause mortality [HR = 1.03,95%CI (1.00, 1.05)]. ROC and calibration curves indicated that HOMA-IR was a reliable predictor of survival status (area under curve = 0,812). No interactions between HOMA-IR and stratified variables were found. Conclusion The relationship between HOMA-IR and all-cause mortality was U-shaped in patients with CHD and hypertension. HOMA-IR was a reliable predictor of all-cause mortality in this population.

Until recently, necrosis is generally regarded as traumatic cell death due to mechanical shear stress or other physicochemical factors, while apoptosis is commonly thought to be programmed cell death, which is silent to immunological response. Actually, multiple modalities of cell death are programmed to maintain systematic immunity. Programmed necrosis, such as necrosis, pyroptosis, and ferroptosis, are inherently more immunogenic than apoptosis. Programmed necrosis leads to the release of inflammatory cytokines, defined as danger-associated molecular patterns (DAMPs), resulting in a necroinflammatory response, which can drive the proinflammatory state under certain biological circumstances. Ferroptosis as a newly discovered non-apoptotic form of cell death, is characterized by excessive lipid peroxidation and overload iron, which occurs in cancer, neurodegeneration, immune and inflammatory diseases, as well as ischemia/reperfusion (I/R) injury. It is triggered by a surplus of reactive oxygen species (ROS) induced in an imbalanced redox reaction due to the decrease in glutathione synthesis and inaction of enzyme glutathione peroxidase 4 (GPX4). Ferroptosis is considered as a potential therapeutic and molecular target for the treatment of necroinflammatory disease, and further investigation into the underlying pathophysiological characteristics and molecular mechanisms implicated may lay the foundations for an interventional therapeutic strategy. This review aims to demonstrate the key roles of ferroptosis in the development of necroinflammatory diseases, the major regulatory mechanisms involved, and its potential as a therapeutic target.

To help doctors and patients evaluate lumbar intervertebral disc degeneration (IVDD) accurately and efficiently, we propose a segmentation network and a quantitation method for IVDD from T2MRI. A semantic segmentation network (BianqueNet) composed of three innovative modules achieves high-precision segmentation of IVDD-related regions. A quantitative method is used to calculate the signal intensity and geometric features of IVDD. Manual measurements have excellent agreement with automatic calculations, but the latter have better repeatability and efficiency. We investigate the relationship between IVDD parameters and demographic information (age, gender, position and IVDD grade) in a large population. Considering these parameters present strong correlation with IVDD grade, we establish a quantitative criterion for IVDD. This fully automated quantitation system for IVDD may provide more precise information for clinical practice, clinical trials, and mechanism investigation. It also would increase the number of patients that can be monitored. Globally, as a major public health problem, low back pain has been the leading cause of disability worldwide for the past 30 years. Here, the authors propose a segmentation network and a quantitative method lumbar intervertebral disc degeneration assessment.

ObjectivesThe tyrosine kinase inhibitor (TKI)-sensitive mutations of the epidermal growth factor receptor (EGFR) gene is essential in the treatment of lung adenocarcinoma. To overcome the difficulty of EGFR gene test in situations where surgery and biopsy samples are too risky to obtain, we tried a noninvasive imaging method using radiomics features and random forest models.MethodsFive hundred three lung adenocarcinoma patients who received surgery-based treatment were included in this study. The diagnosis and EGFR gene test were based on resections. TKI-sensitive mutations were found in 60.8% of the patients. CT scans before any invasive operation were gathered and analyzed to extract quantitative radiomics features and build random forest classifiers to identify EGFR mutants from wild types. Clinical features (sex and smoking history) were added to the image-based model. The model was trained on a set of 345 patients and validated on an independent test group (n = 158) using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity.ResultsThe performance of the random forest model with 94 radiomics features reached an AUC of 0.802. Its AUC was further improved to 0.828 by adding sex and smoking history. The sensitivity and specificity are 60.6% and 85.1% at the best diagnostic decision point.ConclusionOur results showed that radiomics could not only reflect the genetic differences among tumors but also have diagnostic value and the potential to be a diagnostic tool.Key Points• Radiomics provides a potential noninvasive method for the prediction of EGFR mutation status.• In situations where surgeries and biopsy are not available, CT image-based radiomics models could help to make treatment decisions.• The accuracy, sensitivity, and specificity still need to be improved before the image-based EGFR identifier could be used in clinics.

Nuclear receptor coactive 4 (NCOA4), which functions as a selective cargo receptor, is a critical regulator of the particularly autophagic degradation of ferritin, a process known as ferritinophagy. Mechanistically, NCOA4‐mediated ferritinophagy performs an increasingly vital role in the maintenance of intracellular iron homeostasis by promoting ferritin transport and iron release as needed. Ferritinophagy is not only involved in iron‐dependent responses but also in the pathogenesis and progression of various human diseases, including metabolism‐related, neurodegenerative, cardiovascular and infectious diseases. Therefore, ferritinophagy is of great importance in maintaining cell viability and function and represents a potential therapeutic target. Recent studies indicated that ferritinophagy regulates the signalling pathway associated with ferroptosis, a newly discovered type of cell death characterised by iron‐dependent lipid peroxidation. Although accumulating evidence clearly demonstrates the importance of the interplay between dysfunction in iron metabolism and ferroptosis, a deeper understanding of the double‐edged sword effect of ferritinophagy in ferroptosis has remained elusive. Details of the mechanisms underlying the ferritinophagy–ferroptosis axis in regulating relevant human diseases remain to be elucidated. In this review, we discuss the latest research findings regarding the mechanisms that regulate the biological function of NCOA4‐mediated ferritinophagy and its contribution to the pathophysiology of ferroptosis. The important role of the ferritinophagy–ferroptosis axis in human diseases will be discussed in detail, highlighting the great potential of targeting ferritinophagy in the treatment of diseases. Nuclear receptor coactive 4 (NCOA4), served as a selective cargo receptor, is critically responsible for the mediation of autophagic degradation of ferritin that is defined as ferrinnophagy. Mechanically, NCOA4‐mediated ferritinophagy is considered as a pre‐requisite for maintenance of intracellular iron homeostasis by promoting ferritin transport and iron release in accordance with requirements. Therefore, ferritinophagy is of great importance in safeguarding the viability and functionality of cells, and might be a potential therapeutic target for various diseases. In this review, we conclude the latest research findings and regulated mechanisms covering the biological function of NCOA4‐mediated ferritinophagy and its contribution to the pathophysiology of ferroptosis. Moreover, the pivotal role of ferritinophagy–ferroptosis axis in human diseases will be discussed in details, proposing to attract attention on the great potential of ferritinophagy in the treatment of various diseases.

Ferroptosis is a nonapoptotic form of programmed cell death triggered by the accumulation of reactive oxygen species (ROS) depended on iron overload. Although most investigations focus on the relationship between ferroptosis and cancer, neurodegenerative diseases, and ischemia/reperfusion injury, research on ferroptosis induced by immune-related inflammatory diseases, especially sepsis, is scarce. Sestrin2 (Sesn2), a highly evolutionary and stress-responsive protein, is critically involved in defense against oxidative stress challenges. Upregulated expression of Sesn2 has been observed in preliminary experiments to have an antioxidative function in the context of an inflammatory response. Nevertheless, the underlying function of Sesn2 in inflammation-mediated ferroptosis in the immune system remains uncertain. The current study aimed to demonstrate the protective effect of Sesn2 on ferroptosis and even correlations with ferroptosis and the functions of ferroptotic-dendritic cells (DCs) stimulated with lipopolysaccharide (LPS). The mechanism underlying DCs protection from LPS-induced ferroptosis by Sesn2 was further explored in this study. We found that the immune response of DCs assessed by co-stimulatory phenotypes was gradually enhanced at the peak time of 12 h upon 1 μg/ml LPS stimulation while ferroptosis in DCs treated with LPS at 24 h was significantly detected. LPS-induced ferroptosis showed a suppressive impact on DCs in phenotypic maturation, which was conversely relieved by the ferroptotic inhibitor. Compared with wild-type (WT) mice, DCs in genetic defective mice of Sesn2 (Sesn2 −/− ) exhibited exacerbated ferroptosis. Furthermore, the protective effect of Sesn2 on ferroptosis was noticed to be associated with the ATF4-CHOP-CHAC1 pathway, eventually exacerbating ferroptosis by degrading of glutathione. These results indicate that Sesn2 can suppress the ferroptosis of DCs in sepsis by downregulating the ATF4-CHOP-CHAC1 signaling pathway, and it might play an antioxidative role.

The global pandemic of coronavirus disease 2019 (COVID-19) is a disaster for human society. A convenient and reliable neutralization assay is very important for the development of vaccines and novel drugs. In this study, a G protein-deficient vesicular stomatitis virus (VSVdG) bearing a truncated spike protein (S with C-terminal 18 amino acid truncation) was compared to that bearing the full-length spike protein of SARS-CoV-2 and showed much higher efficiency. A neutralization assay was established based on VSV-SARS-CoV-2-Sdel18 pseudovirus and hACE2-overexpressing BHK21 cells (BHK21-hACE2 cells). The experimental results can be obtained by automatically counting the number of EGFP-positive cells at 12 h after infection, making the assay convenient and high-throughput. The serum neutralizing titer measured by the VSV-SARS-CoV-2-Sdel18 pseudovirus assay has a good correlation with that measured by the wild type SARS-CoV-2 assay. Seven neutralizing monoclonal antibodies targeting the receptor binding domain (RBD) of the SARS-CoV-2 S protein were obtained. This efficient and reliable pseudovirus assay model could facilitate the development of new drugs and vaccines.

Hepatitis B virus (HBV) X protein, HBx, interacts with anti-apoptotic Bcl-2 and Bcl-xL proteins through its BH3-like motif to promote HBV replication and cytotoxicity. Here we report the crystal structure of HBx BH3-like motif in complex with Bcl-xL where the BH3-like motif adopts a short α-helix to snuggle into a hydrophobic pocket in Bcl-xL via its noncanonical Trp120 residue and conserved Leu123 residue. This binding pocket is ~2 Å away from the canonical BH3-only binding pocket in structures of Bcl-xL with proapoptotic BH3-only proteins. Mutations altering Trp120 and Leu123 in HBx impair its binding to Bcl-xL in vitro and HBV replication in vivo, confirming the importance of this motif to HBV. A HBx BH3-like peptide, HBx-aa113-135, restores HBV replication from a HBx-null HBV replicon, while a shorter peptide, HBx-aa118-127, inhibits HBV replication. These results provide crucial structural and functional insights into drug designs for inhibiting HBV replication and treating HBV patients. Hepatitis B virus X protein (HBx) binds anti-apoptotic Bcl-xL through its BH3-like motif to promote viral replication. Here, the authors provide the structure of the HBx BH3-like domain and Bcl-xL, which shows an unusual mode of interaction, and identify a short peptide that inhibits HBV replication in cultured human hepatic cells.