Coronaviruses exploit a host cysteine-aspartic protease for replication.

Highly pathogenic coronaviruses, including severe acute respiratory syndrome coronavirus 2 (refs. 1,2) (SARS-CoV-2), Middle East respiratory syndrome coronavirus3 (MERS-CoV) and SARS-CoV-1 (ref. 4), vary in their transmissibility and pathogenicity. However, infection by all three viruses results in substantial apoptosis in cell culture5-7 and in patient tissues8-10, suggesting a potential link between apoptosis and pathogenesis of coronaviruses. Here we show that caspase-6, a cysteine-aspartic protease of the apoptosis cascade, serves as an important host factor for efficient coronavirus replication. We demonstrate that caspase-6 cleaves coronavirus nucleocapsid proteins, generating fragments that serve as interferon antagonists, thus facilitating virus replication. Inhibition of caspase-6 substantially attenuates lung pathology and body weight loss in golden Syrian hamsters infected with SARS-CoV-2 and improves the survival of mice expressing human DPP4 that are infected with mouse-adapted MERS-CoV. Our study reveals how coronaviruses exploit a component of the host apoptosis cascade to facilitate virus replication.

Supertough MXene/Sodium Alginate Composite Fiber Felts Integrated with Outstanding Electromagnetic Interference Shielding and Heating Properties.

The development of multifunctional MXene-based fabrics for smart textiles and portable devices has garnered significant attention. However, very limited studies have focused on their structure design and associated mechanical properties. Here, the supertough MXene fiber felts composed of MXene/sodium alginate (SA) fibers were fabricated. The fracture strength and bending stiffness of felts can be up to 97.8 MPa and 1.04 N mm2, respectively. Besides, the fracture toughness of felts was evaluated using the classic Griffith theory, yielding to a critical stress intensity factor of 1.79 MPam. In addition, this kind of felt presents outstanding electrothermal conversion performance (up to 119 °C at a voltage of 2.5 V), high cryogenic and high-temperature tolerance of photothermal conversion performance (-196 to 160 °C), and excellent electromagnetic interference (EMI) shielding effectiveness (54.4 dB in the X-band). This work provides new structural design concepts for high-performance MXene-based textiles, broadening their future applications.

Hierarchical Assembly of High-Nuclearity Copper(I) Alkynide Nanoclusters: Highly Effective CO2 Electroreduction Catalyst toward Hydrocarbons.

The pursuit of precision in the engineering of metal nanoparticle assemblies has long fascinated scientists, but achieving atomic-level accuracy continues to pose a significant challenge. This research sheds light on the hierarchical assembly processes of two high-nuclearity Cu(I) nanoclusters (NCs). By employing a multiligand cooperative stabilization strategy, we have isolated a series of thiacalix[4]arene (TC4A)/alkynyl coprotected Cu(I) NCs (Cux, where x = 9, 13, 17, 22). These NCs are intricately coassembled from the fundamental building units of {Cu4(TC4A)} and alkynyl-stabilized Cu5L6 in various ratios. By capturing active anion templates such as O2-, Cl-, or C22- that are generated in situ, we have further explored the secondary structural self-assembly of these clusters. Cu13 serves as a secondary assembly module for constructing Cu38 and Cu43, which exhibit the highest nuclearity reported to date among Cu(I) NCs encased in macrocyclic ligands. Notably, Cu38 demonstrates an impressive Faradaic efficiency of 62.01% for hydrocarbons at -1.57 V vs RHE during CO2 electroreduction, with 34.03% for C2H4 and 27.98% for CH4. This performance establishes it as an exceptionally rare, large, atomically precise metal NC (nuclearity >30) capable of catalyzing the formation of highly electro-reduced hydrocarbon products. Our research has introduced a new approach for constructing high-nuclearity Cu(I) NCs through a hierarchical assembly method and investigating their potential in the electrocatalytic transformation of CO2 into hydrocarbons.

PMS2 amplification contributes brain metastasis from lung cancer.

BACKGROUND: Lung adenocarcinoma metastasizing to the brain results in a notable increase in patient mortality. The high incidence and its impact on survival presents a critical unmet need to develop an improved understanding of its mechanisms. METHODS: To identify genes that drive brain metastasis of tumor cells, we collected cerebrospinal fluid samples and paired plasma samples from 114 lung adenocarcinoma patients with brain metastasis and performed 168 panel-targeted gene sequencing. We examined the biological behavior of PMS2 (PMS1 Homolog 2)-amplified lung cancer cell lines through wound healing assays and migration assays. In vivo imaging techniques are used to detect fluorescent signals that colonize the mouse brain. RNA sequencing was used to compare differentially expressed genes between PMS2 amplification and wild-type lung cancer cell lines. RESULTS: We discovered that PMS2 amplification was a plausible candidate driver of brain metastasis. Via in vivo and in vitro assays, we validated that PMS2 amplified PC-9 and LLC lung cancer cells had strong migration and invasion capabilities. The functional pathway of PMS2 amplification of lung cancer cells is mainly enriched in thiamine, butanoate, glutathione metabolism. CONCLUSION: Tumor cells elevated expression of PMS2 possess the capacity to augment the metastatic potential of lung cancer and establish colonies within the brain through metabolism pathways.

Stabilizing the Layer-Structured Oxide Cathode by Modulating the Oxygen Redox Activity for Sodium Ion Batteries.

The layer-structured oxide cathode for sodium-ion batteries has attracted a widespread attention due to the unique redox properties and the anionic redox activity providing additional capacity. Nevertheless, such excessive oxygen redox reactions will lead to irreversible oxygen release, resulting in a rapid deterioration of the cycling stability. Herein, sulfur ion is successfully introduced to the O3-NaNi0.3Mn0.5Cu0.1Ti0.05W0.05O2 material through high-temperature quenching, thereby developing a novel Na2S-modified O3/P2-NaNi0.3Mn0.5Cu0.1Ti0.05W0.05O2 composite with extended cycling life. The S2- is analyzed for the ability to enhance the reversibility of oxidation-reduction reactions under high voltage and suppress the loss of lattice oxygen during cycling. The stable S─O covalent bonds are found to inhibit the oxygen generation and release within the structure. Benefiting from these improvements, the Na2S-modified O3/P2-NaNi0.3Mn0.5Cu0.1Ti0.05W0.05O2 exhibited a high reversible capacity of 173.1 mA h g-1 over a wide voltage range of 1.5-4.3 V under test conditions at 0.1 C and 81.5% capacity retention after 120 cycles at 1 C. The Na2S-modified O3/P2-NaNi0.3Mn0.5Cu0.1Ti0.05W0.05O2 demonstrates the excellent rate capability with the reversible capacities of 173.1,137.0,114.7,96.7, and 80.1 mA h g-1 at 0.1, 0.2, 0.5, 1, and 2 C.

Ultra-Strong Janus Covalent Organic Framework Membrane with Smart Response to Organic Vapor.

Vapor-driven smart Janus materials have made significant advancements in intelligent monitoring, control, and interaction, etc. Nevertheless, the development of ultrafast response single-layer Janus membrane, along with a deep exploration of the smart response mechanisms, remains a long-term endeavor. Here, the successful synthesis of a high-crystallinity single-layer Covalent organic framework (COF) Janus membrane is reported by morphology control. This kind of membrane displays superior mechanical properties and specific surface area, along with excellent responsiveness to CH2Cl2 vapor. The analysis of the underlying mechanisms reveals that the vapor-induced breathing effect of the COF and the stress mismatch of the Janus structure play a crucial role in its smart deformation performance. It is believed that this COF Janus membrane holds promise for complex tasks in various fields.

Additive effect of metabolic dysfunction-associated fatty liver disease on left ventricular function and global strain in type 2 diabetes mellitus patients: a 3.0 T cardiac magnetic resonance feature tracking study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and metabolic-associated fatty liver disease (MAFLD) are both metabolic disorders that negatively impact the cardiovascular system. This study comprehensively analyzed the additive effect of MAFLD on left ventricular function and global strain in T2DM patients by cardiac magnetic resonance (CMR). METHODS: Data of 261 T2DM patients, including 109 with and 152 without MAFLD, as well as 73 matched normal controls from our medical center between June 2015 and March 2022 were retrospectively analyzed. CMR-derived parameters, including LV function and global strain parameters, were compared among different groups. Univariate and multivariate linear regression analyses were conducted to investigate the impact of various factors on LV function and global strain. RESULTS: Our investigation revealed a progressive deterioration in LV functional parameters across three groups: control subjects, T2DM patients without MAFLD, and T2DM patients with MAFLD. Statistically significant increases in left ventricular end-diastolic volume index (LVEDVI), left ventricular end-systolic volume index (LVESVI), left ventricular mass index (LVMI) were observed, along with decreases in left ventricular ejection fraction (LVEF) and left ventricular global function index (LVGFI). Among these three groups, significant reductions were also noted in the absolute values of LV global radial, circumferential, and longitudinal peak strains (GRPS, GCPS, and GLPS), as well as in peak systolic (PSSR) and peak diastolic strain rates (PDSR). MAFLD was identified as an independent predictor of LVEF, LVMI, LVGFI, GRPS, GCPS, and GLPS in multivariate linear analysis. Besides, the incidence of late gadolinium enhancement was higher in MAFLD patients than in non-MAFLD patients (50/109 [45.9%] vs. 42/152 [27.6%], p = 0.003). Furthermore, escalating MAFLD severity was associated with a numerical deterioration in both LV function parameters and global strain values. CONCLUSIONS: This study thoroughly compared CMR parameters in T2DM patients with and without MAFLD, uncovering MAFLD's adverse impact on LV function and deformation in T2DM patients. These findings highlight the critical need for early detection and comprehensive management of cardiac function in T2DM patients with MAFLD.

Sex differences in clinical profile, left ventricular remodeling and cardiovascular outcomes among diabetic patients with heart failure and reduced ejection fraction: a cardiac-MRI-based study.

BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) is associated with a high rate of mortality and morbidity. Evidence has shown that sex differences may be an important contributor to phenotypic heterogeneity in patients with HFrEF. Although diabetes mellitus (DM) frequently coexists with HFrEF and results in a worse prognosis, there remains a need to identify sex-related differences in the characteristics and outcomes of this population. In this study, we aimed to investigate the between-sex differences in clinical profile, left ventricular (LV) remodeling, and cardiovascular risk factors and outcomes in patients with HFrEF concomitant with DM. METHODS: A total of 273 patients with HFrEF concomitant with DM who underwent cardiac MRI were included in this study. Clinical characteristics, LV remodeling as assessed by cardiac MRI, and cardiovascular risk factors and outcomes were compared between sexes. RESULTS: Women were older, leaner and prone to have anemia and hypoproteinemia but less likely to have ischemic etiology. Cardiac MRI revealed that despite similar LVEFs between the sexes, there was more LV concentric remodeling, less impaired global systolic peak strain in longitudinal and circumferential components and a decreased likelihood of late gadolinium enhancement presence in women than in men. During a median follow-up time of 34.6 months, women exhibited better overall survival than men did (log-rank P = 0.042). Multivariable Cox proportional hazards analysis indicated different risk factors for predicting outcomes between sexes, with hypertension [hazard ratio (HR) = 2.05, 95% confidence interval (CI) 1.05 to 4.85, P = 0.041] and hypoproteinemia (HR = 2.27, 95% CI 1.06 to 4.37, P = 0.039) serving as independent determinants of outcomes in women, whereas ischemic etiology (HR = 1.96, 95% CI 1.11 to 3.48, P = 0.021) and atrial fibrillation (HR = 1.86, 95% CI 1.02 to 3.41, P = 0.044) served as independent determinants of outcomes in men. CONCLUSIONS: Among patients with HFrEF concomitant with DM, women displayed different LV remodeling and risk factors and had better survival than men did. Sex-based phenotypic heterogeneity in patients with HFrEF in the context of DM should be addressed in clinical practice.

Reduced thoracic skeletal muscle size is associated with adverse outcomes in diabetes patients with heart failure and reduced ejection fraction: quantitative analysis of sarcopenia by using cardiac MRI.

BACKGROUND: Sarcopenia is frequently found in patients with heart failure with reduced ejection fraction (HFrEF) and is associated with reduced exercise capacity, poor quality of life and adverse outcomes. Recent evidence suggests that axial thoracic skeletal muscle size could be used as a surrogate to assess sarcopenia in HFrEF. Since diabetes mellitus (DM) is one of the most common comorbidities with HFrEF, we aimed to explore the potential association of axial thoracic skeletal muscle size with left ventricular (LV) remodeling and determine its prognostic significance in this condition. METHODS: A total of 243 diabetes patients with HFrEF were included in this study. Bilateral axial thoracic skeletal muscle size was obtained using cardiac MRI. Patients were stratified by the tertiles of axial thoracic skeletal muscle index (SMI). LV structural and functional indices, as well as amino-terminal pro-B-type natriuretic peptide (NT-proBNP), were measured. The determinants of elevated NT-proBNP were assessed using linear regression analysis. The associations between thoracic SMI and clinical outcomes were assessed using a multivariable Cox proportional hazards model. RESULTS: Patients in the lowest tertile of thoracic SMI displayed a deterioration in LV systolic strain in three components, together with an increase in LV mass and a heavier burden of myocardial fibrosis (all P < 0.05). Moreover, thoracic SMI (ß = -0.25; P < 0.001), rather than body mass index (ß = -0.04; P = 0.55), was independently associated with the level of NT-proBNP. The median follow-up duration was 33.6 months (IQR, 20.4-52.8 months). Patients with adverse outcomes showed a lower thoracic SMI (40.1 [34.3, 47.9] cm2/m2 vs. 45.3 [37.3, 55.0] cm2/m2; P < 0.05) but a similar BMI (P = 0.76) compared with those without adverse outcomes. A higher thoracic SMI indicated a lower risk of adverse outcomes (hazard ratio: 0.96; 95% confidence interval: 0.92-0.99; P = 0.01). CONCLUSIONS: With respect to diabetes patients with HFrEF, thoracic SMI is a novel alternative for evaluating muscle wasting in sarcopenia that can be obtained by a readily available routine cardiac MRI protocol. A reduction in thoracic skeletal muscle size predicts poor outcomes in the context of DM with HFrEF.

Left Atrial Phasic Function Impairment in Subacute and Chronic Pulmonary Embolism Patients With Different Degrees of Obstruction: An MRI Feature Tracking Study.

BACKGROUND: The alteration of left atrial (LA) phasic function in subacute and chronic pulmonary embolism (PE) patients is unclear. PURPOSE: To investigate LA phasic strain and LA-right ventricular (RV) interaction in subacute and chronic PE patients with different degrees of obstruction by MRI-feature tracking (MRI-FT). STUDY TYPE: Retrospective. POPULATION: One hundred three PE patients (54 subacute [2 weeks to 3 months after initial symptoms], 49 chronic [>3 months after initial symptoms]) and 80 controls. FIELD STRENGTH/SEQUENCE: 3.0 T/balanced steady state free precession sequence. ASSESSMENT: Patients were divided into mild (pulmonary artery obstruction index [PAOI] < 30%, N = 57), moderate (30% ≤ PAOI < 50%, N = 27), and severe (50% ≥ PAOI, N = 19) PE subgroups. LA reservoir, conduit, and active pump longitudinal strains (εs, εe, and εa) and strain rates (SRs, SRe, and SRa) and biventricular global strains were measured. Determinants of LA strains were investigated. STATISTICAL TESTS: ANOVA, t-tests, Mann-Whitney U tests, linear regression. P < 0.05 was considered statistically significant. RESULTS: For both subacute and chronic PE patients, LA reservoir, conduit, and active pump strains and strain rates were significantly lower than in controls. However, there were no significant differences in LA strains between patients with subacute and chronic PE (P = 0.933, 0.625, and 0.630 for εs, εe, and εa). The severe PE subgroup had significantly higher εa and SRa than the mild and moderate PE subgroups. LA strains were significantly correlated with RV diameter and biventricular strains, and RV diameter (ß = -6.836, -4.084, and -1.899 for εs, εe, and εa) was independently associated with LA strains after adjustment for other factors (R2 = 0.627, 0.536, and 0.437 for εs, εe, and εa). DATA CONCLUSION: LA phasic function evaluated by MRI-FT was significantly impaired in subacute and chronic PE patients, and LA active pump function in the severe PE subgroup was higher than that in the mild and moderate PE subgroups. The independent association between RV diameter and LA strains demonstrates that RV diameter may be an important indicator for monitoring LA dysfunction in PE patients. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.