Biomolecular condensation of ERC1 recruits ATG8 and NBR1 to drive autophagosome formation for plant heat tolerance.

Macroautophagy (hereafter autophagy) is essential for cells to respond to nutrient stress by delivering cytosolic contents to vacuoles for degradation via the formation of a multi-layer vesicle named autophagosome. A set of autophagy-related (ATG) regulators are recruited to the phagophore assembly site for the initiation of phagophore, as well as its expansion and closure and subsequent delivery into the vacuole. However, it remains elusive that how the phagophore assembly is regulated under different stress conditions. Here, we described an unknown Arabidopsis (Arabidopsis thaliana) cytosolic ATG8-interaction protein family (ERC1/2), that binds ATG8 and NBR1 to promote autophagy. ERC1 proteins translocate to the phagophore membrane and develop into classical ring-like autophagosomes upon autophagic induction. However, ERC1 proteins form large droplets together with ATG8e proteins when in the absence of ATG8 lipidation activity. We described the property of these structures as phase-separated membraneless condensates by solving the in vivo organization with spatial and temporal resolution. Moreover, ERC1 condensates elicits a strong recruitment of the autophagic receptor NBR1. Loss of ERC1 suppressed NBR1 turnover and attenuated plant tolerance to heat stress condition. This work provides novel insights into the mechanical principle of phagophore initiation via an unreported ERC1-mediated biomolecular condensation for heat tolerance in Arabidopsis .

Active nitrogen sites on nitrogen doped carbon for highly efficient associative ammonia decomposition.

Nitrogen doped carbon materials have been studied as catalyst support for ammonia decomposition. There are 4 different types of nitrogen environments (graphitic, pyrrolic, pyridinic and nitrogen oxide) on the amorphous support identified. In this paper, we report a 5%Ru on MgCO3 pre-treated nitrogen doped carbon catalyst with high content of edge nitrogen-containing sites which displays an ammonia conversion rate of over 90% at 500°C and WHSV = 30,000 mL gcat -1 h-1. It also gives an impressive hydrogen production rate of 31.3 mmol/(min gcat) with low apparent activation energy of 43 kJ mol-1. Fundamental studies indicate that the distinct average Ru-N4 coordination site on edge regions is responsible for such high catalytic activity. Ammonia is stepwise decomposed via a Ru-N(H)-N(H)-Ru intermediate. This associative mechanism circumvents the direct cleavage of energetic surface nitrogen from metal to form N2 hence lowering the activation barrier for the decomposition over this catalyst.

Comparison of dual-bolus versus dual-sequence techniques for determining myocardial blood flow and myocardial perfusion reserve by cardiac magnetic resonance stress perfusion: From the Automated Quantitative analysis of myocardial perfusion cardiac Magnetic Resonance Consortium.

BACKGROUND: Quantitative stress cardiac magnetic resonance (CMR) can be performed using the dual-sequence (DS) technique or dual-bolus (DB) method. It is unknown if DS and DB produce similar results for myocardial blood flow (MBF) and myocardial perfusion reserve (MPR). The study objective is to investigate if there are any differences between DB- and DS-derived MBF and MPR. METHODS: Retrospective observational study with 168 patients who underwent stress CMR. DB and DS methods were simultaneously performed on each patient on the same day. Global and segmental stress MBF and rest MBF values were collected. RESULTS: Using Bland-Altman analysis, segmental and global stress MBF values were higher in DB than DS (0.22 ± 0.60 mL/g/min, p < 0.001 and 0.20 ± 0.48 mL/g/min, p = 0.005, respectively) with strong correlation (r = 0.81, p < 0.001 for segmental and r = 0.82, p < 0.001 for global). In rest MBF, segmental and global DB values were higher than by DS (0.15 ± 0.51 mL/g/min, p < 0.001 and 0.14 ± 0.36 mL/g/min, p = 0.011, respectively) with strong correlation (r = 0.81, p < 0.001 and r = 0.77, p < 0.001). Mean difference between MPR by DB and DS was -0.02 ± 0.68 mL/g/min (p = 0.758) for segmental values and -0.01 ± 0.49 mL/g/min (p = 0.773) for global values. MPR values correlated strongly as well in both segmental and global, both (r = 0.74, p < 0.001) and (r = 0.75, p < 0.001), respectively. CONCLUSION: There is a very good correlation between DB- and DS-derived MBF and MPR values. However, there are significant differences between DB- and DS-derived global stress and rest MBF. While MPR values did not show statistically significant differences between DB and DS methods.

Prognostic factors in 448 newly diagnosed multiple myeloma receiving bortezomib-based induction: impact of ASCT, transplant refusal and high-risk MM.

In Hong Kong, newly diagnosed multiple myeloma (NDMM) receives bortezomib-based triplet induction. Upfront autologous stem cell transplant (ASCT) is offered to transplant eligible (TE) patients (NDMM ≤ 65 years of age), unless medically unfit (TE-unfit) or refused (TE-refused). Data was retrieved for 448 patients to assess outcomes. For the entire cohort, multivariate analysis showed that male gender (p = 0.006), international staging system (ISS) 3 (p = 0.003), high lactate dehydrogenase (LDH) (p = 7.6 × 10-7) were adverse predictors for overall survival (OS), while complete response/ near complete response (CR/nCR) post-induction (p = 2.7 × 10-5) and ASCT (p = 4.8 × 10-4) were favorable factors for OS. In TE group, upfront ASCT was conducted in 252 (76.1%). Failure to undergo ASCT in TE patients rendered an inferior OS (TE-unfit p = 1.06 × 10-8, TE-refused p = 0.002) and event free survival (EFS) (TE-unfit p = 0.00013, TE-refused p = 0.002). Among TE patients with ASCT, multivariate analysis showed that age ≥ 60 (p = 8.9 × 10-4), ISS 3 (p = 0.019) and high LDH (p = 2.6 × 10-4) were adverse factors for OS. In those with high-risk features (HR cytogenetics, ISS 3, R-ISS 3), ASCT appeared to mitigate their adverse impact. Our data reaffirmed the importance of ASCT. The poor survival inherent with refusal of ASCT should be recognized by clinicians. Finally, improved outcome with ASCT in those with high-risk features warrant further studies.

Prognostic Utility of Left Atrial Strain From MRI Feature Tracking in Ischemic and Nonischemic Dilated Cardiomyopathy: A Multicenter Study.

BACKGROUND. MRI-based prognostic evaluation in patients with dilated cardiomyopathy (DCM) has historically used markers of late gadolinium enhancement (LGE) and feature tracking (FT)-derived left ventricular global longitudinal strain (LVGLS). Early data indicate that FT-derived left atrial strain (LAS) parameters, including reservoir, conduit, and booster, may also have prognostic roles in such patients. OBJECTIVE. The purpose of our study was to evaluate the prognostic utility of LAS parameters, derived from MRI FT, in patients with ischemic or nonischemic DCM, including in comparison with the traditional parameters of LGE and LVGLS. METHODS. This retrospective study included 811 patients with ischemic or nonischemic DCM (median age, 60 years; 640 men, 171 women) who underwent cardiac MRI at any of five centers. FT-derived LAS parameters and LVGLS were measured using two- and four-chamber cine images. LGE percentage was quantified. Patients were assessed for a composite outcome of all-cause mortality or heart failure hospitalization. Multivariable Cox regression analyses including demographic characteristics, cardiovascular risk factors, medications used, and a wide range of cardiac MRI parameters were performed. Kaplan-Meier analyses with log-rank tests were also performed. RESULTS. A total of 419 patients experienced the composite outcome. Patients who did, versus those who did not, experience the composite outcome had larger LVGLS (-6.7% vs -8.3%, respectively; p < .001) as well as a smaller LAS reservoir (13.3% vs 19.3%, p < .001), LAS conduit (4.7% vs 8.0%, p < .001), and LAS booster (8.1% vs 10.3%, p < .001) but no significant difference in LGE (10.1% vs 11.3%, p = .51). In multivariable Cox regression analyses, significant independent predictors of the composite outcome included LAS reservoir (HR = 0.96, p < .001) and LAS conduit (HR = 0.91, p < .001). LAS booster and LGE were not significant independent predictors in the models. LVGLS was a significant independent predictor only in a model that initially included LAS booster but not the other LAS parameters. In Kaplan-Meier analysis, all three LAS parameters were significantly associated with the composite outcome (p < .001). CONCLUSION. In this multicenter study, LAS reservoir and LAS conduit were significant independent prognostic markers in patients with ischemic or nonischemic DCM, showing greater prognostic utility than the currently applied markers of LVGLS and LGE. CLINICAL IMPACT. FT-derived LAS analysis provides incremental prognostic information in patients with DCM.

Altered neutrophil-to-lymphocyte ratio in patients with non-affective first episode psychosis and its relationship with symptom severity and cognitive impairment.

Signatures of immune dysregulation as clinical biomarker for psychosis have remained unclear. We aimed to compare the Neutrophil-to-lymphocyte ratio (NLR) of patients with acute non-affective first-episode psychosis (FEP) with healthy controls after accounting for emotional states. We also explored the associations of NLR with symptom severity, onset profile and cognitive functions. The NLR was enumerated from complete blood count taken within a week of assessment. All FEP patients were rated on the Positive and Negative Syndrome Scale (PANSS) and the Clinician Global Impression-Severity (CGI-S) with verbal memory and executive functions assessed with the Cambridge Neuropsychological Test Automated Battery. Prevailing emotional state was measured with Beck Depression Inventory-II and Beck Anxiety Inventory. Out of seventy-nine consecutive FEP patients presenting to the study site, twenty-seven subjects were eligible and recruited. Twenty-seven age-/sex-matched controls were recruited. FEP patients had an NLR of 1.886 over the controls after accounting for scores on emotional states. The NLR of FEP patients was positively associated with CGI-S scores, PANSS positive symptom, disorganization and excitation scores. There was no significant correlation between NLR with the duration of untreated psychosis and cognitive performances. These findings support using NLR as a clinical biomarker in FEP, purporting further prospective study to measure NLR changes in the course of treatment.

Confined Ru Sites in a 13X Zeolite for Ultrahigh H2 Production from NH3 Decomposition.

Catalytic NH3 synthesis and decomposition offer a new promising way to store and transport renewable energy in the form of NH3 from remote or offshore sites to industrial plants. To use NH3 as a hydrogen carrier, it is important to understand the catalytic functionality of NH3 decomposition reactions at an atomic level. Here, we report for the first time that Ru species confined in a 13X zeolite cavity display the highest specific catalytic activity of over 4000 h-1 for the NH3 decomposition with a lower activation barrier, compared to most reported catalytic materials in the literature. Mechanistic and modeling studies clearly indicate that the N-H bond of NH3 is ruptured heterolytically by the frustrated Lewis pair of Ruδ+-Oδ- in the zeolite identified by synchrotron X-rays and neutron powder diffraction with Rietveld refinement as well as other characterization techniques including solid-state nuclear magnetic resonance spectroscopy, in situ diffuse reflectance infrared transform spectroscopy, and temperature-programmed analysis. This contrasts with the homolytic cleavage of N-H displayed by metal nanoparticles. Our work reveals the unprecedented unique behavior of cooperative frustrated Lewis pairs created by the metal species on the internal zeolite surface, resulting in a dynamic hydrogen shuttling from NH3 to regenerate framework Brønsted acid sites that eventually are converted to molecular hydrogen.

Metal-loaded zeolites in ammonia decomposition catalysis.

The viability of using ammonia as a hydrogen storage vector is contingent on the development of catalytic systems active for ammonia decomposition at low temperatures. Zeolite-supported metal catalysts, unlike systems based on supports like MgO or carbon nanotubes (CNTs), are crystalline and lend themselves to analytic techniques like synchrotron X-ray powder diffraction (SXRD) and Rietveld refinement, allowing precise characterisation of catalytic active sites, and therefore mechanistic elucidation. This study focuses on characterising and optimising novel zeolite-supported Ru catalysts for ammonia decomposition, with a focus on the effects of N-substitution on catalyst structure and activity. Characterisation focuses on an unsubstituted and N-substituted Ru-zeolite Y pair with NMR, FTIR, TEM, XRD, XAS, ICP, and BET, demonstrating the successful incorporation of N into the zeolite framework and an enhancement in metal dispersion upon N-substitution. A series of 18 monometallic and bimetallic catalysts is then synthesised on X and USY supports and screened for catalytic activity. Ru is identified as the most active metal for ammonia decomposition. Observed trends suggest catalyst dispersion can be increased with substantially lower metal loadings, and in particular via the formation of stably anchored oligonuclear metal clusters within the zeolite framework, as opposed to much larger nanoparticles (NPs) on its exterior, following N-substitution of the framework. DFT modelling proposes a prismatic Ru6N6 cluster fitted to XAS data. High-activity catalyst Ru-ß (N) 2.4% demonstrates comparable or better ammonia conversion by Ru wt% than recently reported catalysts in the literature at 450 °C and 30 000 WHSV.

Dispersed surface Ru ensembles on MgO(111) for catalytic ammonia decomposition.

Ammonia is regarded as an energy vector for hydrogen storage, transport and utilization, which links to usage of renewable energies. However, efficient catalysts for ammonia decomposition and their underlying mechanism yet remain obscure. Here we report that atomically-dispersed Ru atoms on MgO support on its polar (111) facets {denoted as MgO(111)} show the highest rate of ammonia decomposition, as far as we are aware, than all catalysts reported in literature due to the strong metal-support interaction and efficient surface coupling reaction. We have carefully investigated the loading effect of Ru from atomic form to cluster/nanoparticle on MgO(111). Progressive increase of surface Ru concentration, correlated with increase in specific activity per metal site, clearly indicates synergistic metal sites in close proximity, akin to those bimetallic N2 complexes in solution are required for the stepwise dehydrogenation of ammonia to N2/H2, as also supported by DFT modelling. Whereas, beyond surface doping, the specific activity drops substantially upon the formation of Ru cluster/nanoparticle, which challenges the classical view of allegorically higher activity of coordinated Ru atoms in cluster form (B5 sites) than isolated sites.

Prevalence, Patterns, and Clinical Severity of Long COVID among Chinese Medicine Telemedicine Service Users: Preliminary Results from a Cross-Sectional Study.

INTRODUCTION: The emergence and persistence of symptoms after acute COVID-19 is expected to become a major burden on healthcare systems. We assessed the features of the post-COVID-19 Syndrome (Long COVID) burden in a cohort of COVID-19 patients during the fifth major wave in Hong Kong. METHODS: A cross-sectional study of 135 patients with confirmed COVID-19 from Feb to Apr 2022 who utilized traditional Chinese medicine telemedicine services was conducted. The COVID-19 Yorkshire Rehabilitation Scale was administered using an online survey 12 weeks after the COVID-19 infection. Prevalence of symptom severity and functional impairments were assessed to identify burdens and patterns. The correlation between symptom severity, functional impairments, patient characteristics, and overall health was evaluated. RESULTS: The mean age was 46.8 years, with 46 (34.1%) males. Symptoms, functional impairments, and overall health worsened significantly when compared to the status prior to the infection. More than 50% reported the following sequelae 12 weeks after the acute infection: breathlessness, laryngeal or airway complications, fatigue, weakness, sleep, cognition, and anxiety. The presence of a single symptom or functional impairment significantly correlated with at least seven other problems positively, except for pain. Severity tended to be higher among vulnerable groups, including those who were chronic disease patients, older, less well educated, female, or had incomplete COVID-19 vaccinations. CONCLUSIONS: Long COVID is a significant healthcare burden among telemedicine users in Hong Kong, with complex needs for symptom and functional impairment management. Designing relevant health and rehabilitation services tailored to the needs of these patients is warranted.