SQSTM1 downregulates avian metapneumovirus subgroup C replication via mediating selective autophagic degradation of viral M2-2 protein.

Avian metapneumovirus subgroup C (aMPV/C), an important pathogen causing acute respiratory infection in chickens and turkeys, contributes to substantial economic losses in the poultry industry worldwide. aMPV/C has been reported to induce autophagy, which is beneficial to virus replication. Sequestosome 1 (SQSTM1/P62), a selective autophagic receptor, plays a crucial role in viral replication by clearing ubiquitinated proteins. However, the relationship between SQSTM1-mediated selective autophagy and aMPV/C replication is unclear. In this study, we found that the expression of SQSTM1 negatively regulates aMPV/C replication by reducing viral protein expression and viral titers. Further studies revealed that the interaction between SQSTM1 and aMPV/C M2-2 protein is mediated via the Phox and Bem1 (PB1) domain of the former, which recognizes a ubiquitinated lysine at position 67 of the M2-2 protein, and finally degrades M2-2 via SQSTM1-mediated selective autophagy. Collectively, our results reveal that SQSTM1 degrades M2-2 via a process of selective autophagy to suppress aMPV/C replication, thereby providing novel insights for the prevention and control of aMPV/C infection.IMPORTANCEThe selective autophagy plays an important role in virus replication. As an emerging pathogen of avian respiratory virus, clarification of the effect of SQSTM1, a selective autophagic receptor, on aMPV/C replication in host cells enables us to better understand the viral pathogenesis. Previous study showed that aMPV/C infection reduced the SQSTM1 expression accompanied by virus proliferation, but the specific regulatory mechanism between them was still unclear. In this study, we demonstrated for the first time that SQSTM1 recognizes the 67th amino acid of M2-2 protein by the interaction between them, followed by M2-2 degradation via the SQSTM1-mediated selective autophagy, and finally inhibits aMPV/C replication. This information supplies the mechanism by which SQSTM1 negatively regulates viral replication, and provides new insights for preventing and controlling aMPV/C infection.

E3 ligase RNF2 inhibits porcine circovirus type 3 replication by targeting its capsid protein for ubiquitination-dependent degradation.

Porcine circovirus type 3 (PCV3) is closely associated with various diseases, such as the porcine dermatitis, nephropathy syndrome, and multisystemic clinicopathological diseases. PCV3-associated diseases are increasingly recognized as severe diseases in the global swine industry. Ring finger protein 2 (RNF2), an E3 ubiquitin ligase exclusively located in the nucleus, contributes to various biological processes. This ligase interacts with the PCV3 Cap. However, its role in PCV3 replication remains unclear. This study confirmed that the nuclear localization signal domain of the Cap and the RNF2 N-terminal RING domain facilitate the interaction between the Cap and RNF2. Furthermore, RNF2 promoted the binding of K48-linked polyubiquitination chains to lysine at positions 139 and 140 (K139 and K140) of the PCV3 Cap, thereby degrading the Cap. RNF2 knockdown and overexpression increased or decreased PCV3 replication, respectively. Moreover, the RING domain-deleted RNF2 mutant eliminated the RNF2-induced degradation of the PCV3 Cap and RNF2-mediated inhibition of viral replication. This indicates that both processes were associated with its E3 ligase activity. Our findings demonstrate that RNF2 can interact with and degrade the PCV3 Cap via its N-terminal RING domain in a ubiquitination-dependent manner, thereby inhibiting PCV3 replication.IMPORTANCEPorcine circovirus type 3 is a recently described pathogen that is prevalent worldwide, causing substantial economic losses to the swine industry. However, the mechanisms through which host proteins regulate its replication remain unclear. Here, we demonstrate that ring finger protein 2 inhibits porcine circovirus type 3 replication by interacting with and degrading the Cap of this pathogen in a ubiquitination-dependent manner, requiring its N-terminal RING domain. Ring finger protein 2-mediated degradation of the Cap relies on its E3 ligase activity and the simultaneous existence of K139 and K140 within the Cap. These findings reveal the mechanism by which this protein interacts with and degrades the Cap to inhibit porcine circovirus type 3 replication. This consequently provides novel insights into porcine circovirus type 3 pathogenesis and facilitates the development of preventative measures against this pathogen.

Neutron Scattering Studies of Heterogeneous Catalysis.

Understanding the structural dynamics/evolution of catalysts and the related surface chemistry is essential for establishing structure-catalysis relationships, where spectroscopic and scattering tools play a crucial role. Among many such tools, neutron scattering, though less-known, has a unique power for investigating catalytic phenomena. Since neutrons interact with the nuclei of matter, the neutron-nucleon interaction provides unique information on light elements (mainly hydrogen), neighboring elements, and isotopes, which are complementary to X-ray and photon-based techniques. Neutron vibrational spectroscopy has been the most utilized neutron scattering approach for heterogeneous catalysis research by providing chemical information on surface/bulk species (mostly H-containing) and reaction chemistry. Neutron diffraction and quasielastic neutron scattering can also supply important information on catalyst structures and dynamics of surface species. Other neutron approaches, such as small angle neutron scattering and neutron imaging, have been much less used but still give distinctive catalytic information. This review provides a comprehensive overview of recent advances in neutron scattering investigations of heterogeneous catalysis, focusing on surface adsorbates, reaction mechanisms, and catalyst structural changes revealed by neutron spectroscopy, diffraction, quasielastic neutron scattering, and other neutron techniques. Perspectives are also provided on the challenges and future opportunities in neutron scattering studies of heterogeneous catalysis.

Critical Role of Framework Flexibility and Disorder in Driving High Ionic Conductivity in LiNbOCl4.

Understanding Li-ion transport is key for the rational design of superionic solid electrolytes with exceptional ionic conductivities. LiNbOCl4 is reported to be one of the most highly conducting materials in the recently realized new class of soft oxyhalide solid electrolytes, exhibiting an ionic conductivity of ∼11 mS·cm-1. Here, we apply X-ray/neutron diffraction and pair distribution function analysis─coupled with density functional theory/ab initio molecular dynamics (AIMD)─to determine a structural model that provides a rationale for the high conductivity that we observe experimentally in this nanocrystalline solid. We show that it arises from unusually high framework flexibility at room temperature. This is due to isolated 1-D [NbOCl4]- anionic chains that exhibit energetically favorable orientational disorder that is─in turn─correlated to multiple, disordered, and equi-energetic Li+ sites in the lattice. As the Li ions sample the 3-D energy landscape with a fast predicted diffusion coefficient of 5.1 × 10-7 cm2/s at room temperature (σicalc = 17.4 mS·cm-1), the inorganic polymer chains can reorient or vice versa. The activation energy barrier for Li migration through the frustrated energy landscape is especially reduced by the elastic nature of the NbO2Cl4 octahedra evident from very widely dispersed Cl-Nb-Cl bond angles in AIMD simulations at 300 K. The phonon spectra are predominantly influenced by Cl vibrations in the low energy range, and there is a strong overlap between the framework (Cl, Nb) and Li partial density of states in the region between 1.2 and 4.0 THz. The framework flexibility is also reflected in a relatively low bulk modulus of 22.7 GPa. Our findings pave the way for the investigation of future "flex-ion" inorganic solids and open up a new direction for the design of high-conductivity, soft solid electrolytes for all-solid-state batteries.

Boosting Energy-Storage in High-Entropy Pb-Free Relaxors Engineered by Local Lattice Distortion.

The high-entropy strategy has shown potential in advancing the energy-storage performance of dielectric capacitors, offering benefits to a range of electronic and electrical systems. However, designing high-performance high-entropy relaxor ferroelectrics (RFEs) presents challenges due to the unclear correlation between their core effects and local polarization heterogeneity. Here, we demonstrate that by engineering the local lattice distortion, a core effect in high-entropy systems, to manipulate the local polarization configuration, a giant energy density (Wrec) of 18.7 J cm-3 and high efficiency (η) of 85% can be achieved in (Bi0.5K0.5)TiO3-based high-entropy bulk RFE ceramics. Atomic-level local structural analysis unveils that the local lattice distortion field can be flattened by introducing ions with less size mismatch. The increase in configurational entropy from 1.54 to 2.06R is associated with a smoother polar displacement vector field and a reduction in the size of polar clusters to several unit-cell sizes with weak coupling. Consequently, a substantial decrease in hysteresis and an enhancement in the breakdown field strength can be obtained, leading to a significant improvement in energy density by over 6 times and efficiency by 3 times. Our research establishes a relationship between local lattice distortion, atomic polar displacement, and energy-storage performance in complex high-entropy systems, providing insights for enhancing energy-storage performance via a local structure design.

Influence of Interlayer Cation Ordering on Na Transport in P2-Type Na0.67-xLiy Ni0.33-zMn0.67+zO2 for Sodium-Ion Batteries.

P2-type Na2/3Ni1/3Mn2/3O2 (PNNMO) has been extensively studied because of its desirable electrochemical properties as a positive electrode for sodium-ion batteries. PNNMO exhibits intralayer transition-metal ordering of Ni and Mn and intralayer Na+/vacancy ordering. The Na+/vacancy ordering is often considered a major impediment to fast Na+ transport and can be affected by transition-metal ordering. We show by neutron/X-ray diffraction and density functional theory (DFT) calculations that Li doping (Na2/3Li0.05Ni1/3Mn2/3O2, LFN5) promotes ABC-type interplanar Ni/Mn ordering without disrupting the Na+/vacancy ordering and creates low-energy Li-Mn-coordinated diffusion pathways. A structure model is developed to quantitatively identify both the intralayer cation mixing and interlayer cationic stacking fault densities. Quasielastic neutron scattering reveals that the Na+ diffusivity in LFN5 is enhanced by an order of magnitude over PNNMO, increasing its capacity at a high current. Na2/3Ni1/4Mn3/4O2 (NM13) lacks Na+/vacancy ordering but has diffusivity comparable to that of LFN5. However, NM13 has the smallest capacity at a high current. The high site energy of Mn-Mn-coordinated Na compared to that of Ni-Mn and higher density of Mn-Mn-coordinated Na+ sites in NM13 disrupts the connectivity of low-energy Ni-Mn-coordinated diffusion pathways. These results suggest that the interlayer ordering can be tuned through the control of composition, which has an equal or greater impact on Na+ diffusion than the Na+/vacancy ordering.

Revealing the Chemical and Structural Complexity of Electrochemical Ion Exchange in Layered Oxide Materials.

Soft chemistry techniques, such as ion exchange, hold great potential for the development of battery electrode materials that cannot be stabilized via conventional equilibrium synthesis methods. Nevertheless, the intricate mechanisms governing ion exchange remain elusive. Herein, we investigate the evolution of the long-range and local structure, as well as the ion (de)intercalation mechanism during electrochemical Li-to-Na ion exchange initiated from an O3-type lithium-layered oxide cathode. The in situ-formed mixed-cation electrolyte leads to competitive intercalation of Li and Na ions. While Li ion intercalation predominates at the beginning of initial discharge, Na ion cointercalation into a different layer results in ion redistribution and phase separation, with the emergence of a P3-Na phase alongside an O3-Li phase. Further, this study spatially resolves the heterogeneous nature of electrochemical ion exchange reactions within individual particles and provides insights into the correlations between local Ni redox processes and phase separation. Overall, electrochemical ion exchange leads to a mixed-phase cathode and alters its reaction kinetics. Those findings have important implications for the development of new metastable materials for renewable energy devices and ion separation applications.

Displacive Jahn-Teller Transition in NaNiO2.

Below its Jahn-Teller transition temperature, TJT, NaNiO2 has a monoclinic layered structure consisting of alternating layers of edge-sharing NaO6 and Jahn-Teller-distorted NiO6 octahedra. Above TJT where NaNiO2 is rhombohedral, diffraction measurements show the absence of a cooperative Jahn-Teller distortion, accompanied by an increase in the unit cell volume. Using neutron total scattering, solid-state Nuclear Magnetic Resonance (NMR), and extended X-ray absorption fine structure (EXAFS) experiments as local probes of the structure we find direct evidence for a displacive, as opposed to order-disorder, Jahn-Teller transition at TJT. This is supported by ab initio molecular dynamics (AIMD) simulations. To our knowledge this study is the first to show a displacive Jahn-Teller transition in any material using direct observations with local probe techniques.

Outstanding Energy-Storage Density Together with Efficiency of above 90% via Local Structure Design.

Dielectric ceramic capacitors with high recoverable energy density (Wrec) and efficiency (η) are of great significance in advanced electronic devices. However, it remains a challenge to achieve high Wrec and η parameters simultaneously. Herein, based on density functional theory calculations and local structure analysis, the feasibility of developing the aforementioned capacitors is demonstrated by considering Bi0.25Na0.25Ba0.5TiO3 (BNT-50BT) as a matrix material with large local polarization and structural distortion. Remarkable Wrec and η of 16.21 J/cm3 and 90.5% have been achieved in Bi0.25Na0.25Ba0.5Ti0.92Hf0.08O3 via simple chemical modification, which is the highest Wrec value among reported bulk ceramics with η greater than 90%. The examination results of local structures at lattice and atomic scales indicate that the disorderly polarization distribution and small nanoregion (∼3 nm) lead to low hysteresis and high efficiency. In turn, the drastic increase in local polarization activated via the ultrahigh electric field (80 kV/mm) leads to large polarization and superior energy storage density. Therefore, this study emphasizes that chemical design should be established on a clear understanding of the performance-related local structure to enable a targeted regulation of high-performance systems.

Effects of physical and psychological multimorbidity on the risk of dementia: multinational prospective cohorts and a meta-analysis.

BACKGROUND: Previous studies only considered the impact of a single physical or psychological disorder on dementia. Our study investigated the association of physical and psychological multimorbidity with dementia among older adults using two multinational prospective cohorts to supplement the limited joint evidence. METHODS: We utilized the Health and Retirement Study (HRS 2012 to 2018) in the United States (US) and the Survey of Health, Ageing and Retirement in Europe (SHARE 2012 to 2018). Physical disorder was defined as any one of seven self-reported physician-diagnosed conditions. Psychological disorder was assessed using the 8-item Center for Epidemiologic Research Depression (CES-D) scale or the EURO-D. Dementia was determined through a combination of self-reported physician diagnosis of dementia or Alzheimer's disease, or the 27-point HRS cognitive scale. Competing risk models were utilized to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CI). DerSimonian-Laird random-effects meta-analyses were conducted to obtain pooled estimates. RESULTS: The prevalence of physical and psychological multimorbidity was 17.29% (1027/5939) in continental Europe and 15.52% (1326/8543) in the US. The incidence of dementia was 6.21 per 1000 person-years in continental Europe and 8.27 per 1000 person-years in the US, respectively. It was highest among participants with physical and psychological multimorbidity in continental Europe (10.46 per 1000 person-years) and the US (14.82 per 1000 person-years), compared with the other three groups. In the univariate model, participants who reported physical and psychological multimorbidity had a higher risk of dementia compared with those who reported no physical and psychological disorders in continental Europe (HR = 2.59; 95% CI: 1.55, 4.33) and the US (HR = 4.11; 95% CI: 2.44, 6.94). After adjusting all covariates, the risk of dementia among participants who reported physical and psychological multimorbidity increased by 86% in continental Europe (aHR = 1.86; 95% CI: 1.08, 3.21) and by 176% in the US (aHR = 2.76; 95% CI: 1.61, 4.72), respectively. After pooling the outcomes, the risk of dementia among participants who reported physical and psychological multimorbidity increased by 115% (aHR = 2.15; 95% CI: 1.27, 3.03). CONCLUSIONS: Physical and psychological multimorbidity was prevalent among older adults in the US and continental Europe. Given the consistent associations with dementia, it is imperative to increase awareness of the links and recognize the limitations of single-disorder care. Specific attention should be given to providing care coordination.

Trajectories of health conditions and their associations with the risk of cognitive impairment among older adults: insights from a national prospective cohort study.

BACKGROUND: The associations between trajectories of different health conditions and cognitive impairment among older adults were unknown. Our cohort study aimed to investigate the impact of various trajectories, including sleep disturbances, depressive symptoms, functional limitations, and multimorbidity, on the subsequent risk of cognitive impairment. METHODS: We conducted a prospective cohort study by using eight waves of national data from the Health and Retirement Study (HRS 2002-2018), involving 4319 adults aged 60 years or older in the USA. Sleep disturbances and depressive symptoms were measured using the Jenkins Sleep Scale and the Centers for Epidemiologic Research Depression (CES-D) scale, respectively. Functional limitations were assessed using activities of daily living (ADLs) and instrumental activities of daily living (IADLs), respectively. Multimorbidity status was assessed by self-reporting physician-diagnosed diseases. We identified 8-year trajectories at four examinations from 2002 to 2010 using latent class trajectory modeling. We screened participants for cognitive impairment using the 27-point HRS cognitive scale from 2010 to 2018 across four subsequent waves. We calculated hazard ratios (HR) using Cox proportional hazard models. RESULTS: During 25,914 person-years, 1230 participants developed cognitive impairment. In the fully adjusted model 3, the trajectories of sleep disturbances and ADLs limitations were not associated with the risk of cognitive impairment. Compared to the low trajectory, we found that the increasing trajectory of depressive symptoms (HR = 1.39; 95% CI = 1.17-1.65), the increasing trajectory of IADLs limitations (HR = 1.88; 95% CI = 1.43-2.46), and the high trajectory of multimorbidity status (HR = 1.48; 95% CI = 1.16-1.88) all posed an elevated risk of cognitive impairment. The increasing trajectory of IADLs limitations was associated with a higher risk of cognitive impairment among older adults living in urban areas (HR = 2.30; 95% CI = 1.65-3.21) and those who smoked (HR = 2.77; 95% CI = 1.91-4.02) (all P for interaction < 0.05). CONCLUSIONS: The results suggest that tracking trajectories of depressive symptoms, instrumental functioning limitations, and multimorbidity status may be a potential and feasible screening method for identifying older adults at risk of cognitive impairment.

Seneca Valley virus 3Cpro antagonizes type I interferon response by targeting STAT1-STAT2-IRF9 and KPNA1 signals.

IMPORTANCE: Type I interferon (IFN) signaling plays a principal role in host innate immune responses against invading viruses. Viruses have evolved diverse mechanisms that target the Janus kinase-signal transducer and activator of transcription (STAT) signaling pathway to modulate IFN response negatively. Seneca Valley virus (SVV), an emerging porcine picornavirus, has received great interest recently because it poses a great threat to the global pork industry. However, the molecular mechanism by which SVV evades host innate immunity remains incompletely clear. Our results revealed that SVV proteinase (3Cpro) antagonizes IFN signaling by degrading STAT1, STAT2, and IRF9, and cleaving STAT2 to escape host immunity. SVV 3Cpro also degrades karyopherin 1 to block IFN-stimulated gene factor 3 nuclear translocation. Our results reveal a novel molecular mechanism by which SVV 3Cpro antagonizes the type I IFN response pathway by targeting STAT1-STAT2-IRF9 and karyopherin α1 signals, which has important implications for our understanding of SVV-evaded host innate immune responses.

Ubiquitination-dependent degradation of nucleolin mediated by porcine circovirus type 3 capsid protein.

IMPORTANCE: Porcine circovirus type 3 (PCV3) is an emerging pathogen that causes multisystem disease in pigs and poses a severe threat to the swine industry. However, the mechanisms of how PCV3 uses host proteins to regulate its own life cycle are not well understood. In this study, we found that PCV3 capsid protein interacts with nucleolin and degrades it. Degradation of nucleolin by the PCV3 capsid protein requires recruitment of the enzyme RNF34, which is transported to the nucleolus from the cytoplasm in the presence of the PCV3 capsid protein. Nucleolin also decreases PCV3 replication by promoting the release of interferon ß. These findings clarify the mechanism by which nucleolin modulates PCV3 replication in cells, thereby facilitating to provide an important strategy for preventing and controlling PCV3 infection.

ANGPTL4 accelerates ovarian serous cystadenocarcinoma carcinogenesis and angiogenesis in the tumor microenvironment by activating the JAK2/STAT3 pathway and interacting with ESM1.

BACKGROUND: Ovarian cancer (OC) is a malignant neoplasm that displays increased vascularization. Angiopoietin-like 4 (ANGPTL4) is a secreted glycoprotein that functions as a regulator of cell metabolism and angiogenesis and plays a critical role in tumorigenesis. However, the precise role of ANGPTL4 in the OC microenvironment, particularly its involvement in angiogenesis, has not been fully elucidated. METHODS: The expression of ANGPTL4 was confirmed by bioinformatics and IHC in OC. The potential molecular mechanism of ANGPTL4 was measured by RNA-sequence. We used a series of molecular biological experiments to measure the ANGPTL4-JAK2-STAT3 and ANGPTL4-ESM1 axis in OC progression, including MTT, EdU, wound healing, transwell, xenograft model, oil red O staining, chick chorioallantoic membrane assay and zebrafish model. Moreover, the molecular mechanisms were confirmed by Western blot, Co-IP and molecular docking. RESULTS: Our study demonstrates a significant upregulation of ANGPTL4 in OC specimens and its strong association with unfavorable prognosis. RNA-seq analysis affirms that ANGPTL4 facilitates OC development by driving JAK2-STAT3 signaling pathway activation. The interaction between ANGPTL4 and ESM1 promotes ANGPTL4 binding to lipoprotein lipase (LPL), thereby resulting in reprogrammed lipid metabolism and the promotion of OC cell proliferation, migration, and invasion. In the OC microenvironment, ESM1 may interfere with the binding of ANGPTL4 to integrin and vascular-endothelial cadherin (VE-Cad), which leads to stabilization of vascular integrity and ultimately promotes angiogenesis. CONCLUSION: Our findings underscore that ANGPTL4 promotes OC development via JAK signaling and induces angiogenesis in the tumor microenvironment through its interaction with ESM1.

Characterizing the metabolic divide: distinctive metabolites differentiating CAD-T2DM from CAD patients.

OBJECTIVE: To delineate the metabolomic differences in plasma samples between patients with coronary artery disease (CAD) and those with concomitant CAD and type 2 diabetes mellitus (T2DM), and to pinpoint distinctive metabolites indicative of T2DM risk. METHOD: Plasma samples from CAD and CAD-T2DM patients across three centers underwent comprehensive metabolomic and lipidomic analyses. Multivariate logistic regression was employed to discern the relationship between the identified metabolites and T2DM risk. Characteristic metabolites' metabolic impacts were further probed through hepatocyte cellular experiments. Subsequent transcriptomic analyses elucidated the potential target sites explaining the metabolic actions of these metabolites. RESULTS: Metabolomic analysis revealed 192 and 95 significantly altered profiles in the discovery (FDR < 0.05) and validation (P < 0.05) cohorts, respectively, that were associated with T2DM risk in univariate logistic regression. Further multivariate regression analyses identified 22 characteristic metabolites consistently associated with T2DM risk in both cohorts. Notably, pipecolinic acid and L-pipecolic acid, lysine derivatives, exhibited negative association with CAD-T2DM and influenced cellular glucose metabolism in hepatocytes. Transcriptomic insights shed light on potential metabolic action sites of these metabolites. CONCLUSIONS: This research underscores the metabolic disparities between CAD and CAD-T2DM patients, spotlighting the protective attributes of pipecolinic acid and L-pipecolic acid. The comprehensive metabolomic and transcriptomic findings provide novel insights into the mechanism research, prophylaxis and treatment of comorbidity of CAD and T2DM.

Association between parity and female mortality: the mediative role of depressive symptoms.

STUDY QUESTION: Is parity associated with all-cause and cause-specific mortality among women in a nationally representative cohort of the US population, and does depression mediate this association? SUMMARY ANSWER: Nulliparous women have a higher risk of all-cause and cause-specific mortality, with depression partially mediating the relationship between parity and women's all-cause and cause-specific mortality. WHAT IS KNOWN ALREADY: Parity, a significant state in reproductive life, has enduring implications for women's health. There is also a complex relationship between depression, a prevalent mental and emotional disorder, and female fertility. Previous studies have elucidated the relationships between parity and depression, both of which are associated with mortality. However, findings from studies examining parity and women's mortality have been inconsistent. Moreover, few studies have investigated whether the effect of parity on mortality is mediated by depression. STUDY DESIGN, SIZE, DURATION: We conducted a cross-sectional study using data from seven cycles of the National Health and Nutrition Examination Survey (NHANES) spanning 2005-2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study cohort comprised adult women with available parity and survival follow-up data. Parity data were self-reported and sourced from the Reproductive Health Questionnaire. Depression scores were derived from the Patient Health Questionnaire 9, and cause-specific deaths were identified using the International Statistical Classification of Diseases, 10th Revision (ICD-10). Weighted multivariable Cox regression was applied to analyze the association between parity, depression, and mortality. Weighted linear regression was performed to examine the relationship between parity and depression. Mediation analyses were employed to determine whether and to what extent depression mediated the effect of parity on mortality. MAIN RESULTS AND THE ROLE OF CHANCE: Our study ultimately encompassed 16 962 American women. Following multivariable adjustment, compared to nulliparous women, those with one to three live births exhibited a 17% and 33% reduction in all-cause and cancer mortality, respectively (all-cause mortality: HR = 0.83, 95% CI = 0.69-0.99, P = 0.040; cancer mortality: HR = 0.67, 95% CI = 0.45-0.99, P = 0.045). Women with more than four live births demonstrated lower all-cause mortality and mortality from other (not cancer or cardiovascular disease) diseases (all-cause mortality: HR = 0.73, 95% CI = 0.58-0.93, P = 0.011; other diseases mortality: HR = 0.66, 95% CI = 0.47-0.91, P = 0.013). No correlation was detected between parity and the risk of cardiovascular disease mortality among women. Furthermore, depression was found to partially mediate the impact of parity on all-cause mortality and mortality from other diseases in women. LIMITATIONS, REASONS FOR CAUTION: Firstly, a single index of parity was used as an exposure factor, and other reproductive factors such as birth spacing, age at first birth, and mode of delivery were not taken into account. Secondly, despite accounting for important potentially confounders in our analysis, such as BMI, smoking status, and educational level, the influence of unmeasured confounders (e.g., social class, latent reproductive system diseases) on reproductive behavior or mortality cannot be dismissed. Thirdly, women's vulnerability to depression fluctuates across reproductive stages, and the effect of depression on female fertility varies over time. Due to data constraints, we were unable to obtain information on women's mental health status at different reproductive stages. Fourthly, due to the data accessibility limitations of NHANES, we were unable to specifically explore the relationship between parity and different specific types of cancer, a limitation that may obscure potential correlations. Additionally, despite our efforts to control for various confounding factors in subgroup analyses, the smaller sample sizes in some subgroups may limit the statistical power, affecting the ability to detect effects. Finally, studies exploring the association between parity and depression are cross-sectional designs, making it difficult to infer causality. These results should be interpreted with caution, and further research is warranted to corroborate our findings. WIDER IMPLICATIONS OF THE FINDINGS: Our study underscores the elevated risk of all-cause and cause-specific mortality in nulliparous women and reveals that depression partially mediates the negative correlation between parity and women's all-cause mortality and mortality from other diseases. These results should be interpreted with caution, and further investigation is needed to support our findings. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Key Research and Development Program of China (2023YFC2705700), the Key Research & Developmental Program of Hubei Province (2022BCA042), and the Interdisciplinary Innovative Talents Foundation from Renmin Hospital of Wuhan University (JCRCWL-2022-001). The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Seneca valley virus 3C protease blocks EphA2-Mediated mTOR activation to facilitate viral replication.

The Seneca Valley virus (SVV) is a recently discovered porcine pathogen that causes vesicular diseases and poses a significant threat to the pig industry worldwide. Erythropoietin-producing hepatoma receptor A2 (EphA2) is involved in the activation of the AKT/mTOR signaling pathway, which is involved in autophagy. However, the regulatory relationship between SVV and EphA2 remains unclear. In this study, we demonstrated that EphA2 is proteolysed in SVV-infected BHK-21 and PK-15 cells. Overexpression of EphA2 significantly inhibited SVV replication, as evidenced by decreased viral protein expression, viral titers, and viral load, suggesting an antiviral function of EphA2. Subsequently, viral proteins involved in the proteolysis of EphA2 were screened, and the SVV 3C protease (3Cpro) was found to be responsible for this cleavage, depending on its protease activity. However, the protease activity sites of 3Cpro did not affect the interactions between 3Cpro and EphA2. We further determined that EphA2 overexpression inhibited autophagy by activating the mTOR pathway and suppressing SVV replication. Taken together, these results indicate that SVV 3Cpro targets EphA2 for cleavage to impair its EphA2-mediated antiviral activity and emphasize the potential of the molecular interactions involved in developing antiviral strategies against SVV infection.

Exotic Magnetism in Perovskite KOsO_{3}.

A new perovskite KOsO_{3} has been stabilized under high-pressure and high-temperature conditions. It is cubic at 500 K (Pm-3m) and undergoes subsequent phase transitions to tetragonal at 320 K (P4/mmm) and rhombohedral (R-3m) at 230 K as shown from refining synchrotron x-ray powder diffraction (SXRD) data. The larger orbital overlap integral and the extended wave function of 5d electrons in the perovskite KOsO_{3} allow to explore physics from the regime where Mott and Hund's rule couplings dominate to the state where the multiple interactions are on equal footing. We demonstrate an exotic magnetic ordering phase found by neutron powder diffraction along with physical properties via a suite of measurements including magnetic and transport properties, differential scanning calorimetry, and specific heat, which provide comprehensive information for a system at the crossover from localized to itinerant electronic behavior.

Global, regional and national trends and impacts of natural floods, 1990-2022.

Objective: To assess global, regional and national trends in the impact of floods from 1990 to 2022 and determine factors influencing flood-related deaths. Methods: We used data on flood disasters from the International Disaster Database for 1990-2022 from 168 countries. We calculated the annual percentage change to estimate trends in the rates of people affected and killed by floods by study period, World Health Organization (WHO) region, country income level and flood type. We used multivariable logistic regression analysis to assess the factors associated with death from floods. Findings: From 1990 to 2022, 4713 floods were recorded in 168 countries, which affected > 3.2 billion people, caused 218 353 deaths and were responsible for more than 1.3 trillion United States dollars of economic losses. The WHO Western Pacific Region had the most people affected by floods (> 2.0 billion), accounting for 63.19% (2 024 599 380/3 203 944 965) of all affected populations. The South-East Asia Region had the most deaths (71 713, 32.84%). The African and Eastern Mediterranean Regions had the highest number of people affected and killed by floods per 100 000 population in 2022. The odds of floods causing more than 50 deaths were significantly higher in low-income countries (adjusted odds ratio: 14.34; 95% confidence interval: 7.46 to 30.04) compared with high-income countries. Numbers of people affected and mortality due to floods declined over time. Conclusion: Despite the decreases in populations affected and deaths, floods still have a serious impact on people and economies globally, particularly in lower-income countries. Action is needed to improve disaster risk management and flood mitigation.

Prenatal Diagnosis of Placenta Accreta Spectrum Disorders: Deep Learning Radiomics of Pelvic MRI.

BACKGROUND: Diagnostic performance of placenta accreta spectrum (PAS) by prenatal MRI is unsatisfactory. Deep learning radiomics (DLR) has the potential to quantify the MRI features of PAS. PURPOSE: To explore whether DLR from MRI can be used to identify pregnancies with PAS. STUDY TYPE: Retrospective. POPULATION: 324 pregnant women (mean age, 33.3 years) suspected PAS (170 training and 72 validation from institution 1, 82 external validation from institution 2) with clinicopathologically proved PAS (206 PAS, 118 non-PAS). FIELD STRENGTH/SEQUENCE: 3-T, turbo spin-echo T2-weighted images. ASSESSMENT: The DLR features were extracted using the MedicalNet. An MRI-based DLR model incorporating DLR signature, clinical model (different clinical characteristics between PAS and non-PAS groups), and MRI morphologic model (radiologists' binary assessment for the PAS diagnosis) was developed. These models were constructed in the training dataset and then validated in the validation datasets. STATISTICAL TESTS: The Student t-test or Mann-Whitney U, χ2 or Fisher exact test, Kappa, dice similarity coefficient, intraclass correlation coefficients, least absolute shrinkage and selection operator logistic regression, multivariate logistic regression, receiver operating characteristic (ROC) curve, DeLong test, net reclassification improvement (NRI) and integrated discrimination improvement (IDI), calibration curve with Hosmer-Lemeshow test, decision curve analysis (DCA). P < 0.05 indicated a significant difference. RESULTS: The MRI-based DLR model had a higher area under the curve than the clinical model in three datasets (0.880 vs. 0.741, 0.861 vs. 0.772, 0.852 vs. 0.675, respectively) or MRI morphologic model in training and independent validation datasets (0.880 vs. 0.760, 0.861, vs. 0.781, respectively). The NRI and IDI were 0.123 and 0.104, respectively. The Hosmer-Lemeshow test had nonsignificant statistics (P = 0.296 to 0.590). The DCA offered a net benefit at any threshold probability. DATA CONCLUSION: An MRI-based DLR model may show better performance in diagnosing PAS than a clinical or MRI morphologic model. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.