SIRT1 deacetylates WEE1 and sensitizes cancer cells to WEE1 inhibition.

The cell-cycle checkpoint kinase WEE1 is emerging as a therapeutic target for cancer treatment. However, how its catalytic activity is regulated remains poorly understood, and reliable biomarkers for predicting response to WEE1 inhibitor remain to be identified. Here we identify an evolutionarily conserved segment surrounding its Lys177 residue that inhibits WEE1 activity through an intermolecular interaction with the catalytic kinase domain. Upon DNA damage, CHK1-dependent phosphorylation of WEE1 at Ser642 primes GCN5-mediated acetylation at Lys177, resulting in dissociation of the inhibitory segment from the kinase domain and subsequent activation of WEE1 and cell-cycle checkpoints. Conversely, SIRT1 associates with and deacetylates WEE1, which maintains it in an inactive state. Consequently, SIRT1 deficiency induces WEE1 hyperacetylation and activation, rendering cancer cells resistant to WEE1 inhibition. These results suggest that SIRT1 expression level and abundance of WEE1 Lys177 acetylation in tumor cells can serve as useful biomarkers for predicting WEE1 inhibitor sensitivity or resistance.

Topology, vorticity, and limit cycle in a stabilized Kuramoto-Sivashinsky equation.

A noisy stabilized Kuramoto-Sivashinsky equation is analyzed by stochastic decomposition. For values of the control parameter for which periodic stationary patterns exist, the dynamics can be decomposed into diffusive and transverse parts which act on a stochastic potential. The relative positions of stationary states in the stochastic global potential landscape can be obtained from the topology spanned by the low-lying eigenmodes which interconnect them. Numerical simulations confirm the predicted landscape. The transverse component also predicts a universal class of vortex-like circulations around fixed points. These drive nonlinear drifting and limit cycle motion of the underlying periodic structure in certain regions of parameter space. Our findings might be relevant in studies of other nonlinear systems such as deep learning neural networks.

Unveiling the Occurrence and Non-Negligible Role of Amino Sugars in Waste Activated Sludge Fermentation by an Enriched Chitin-Degradation Consortium.

Polysaccharides in extracellular polymeric substances (EPS) can form a hybrid matrix network with proteins, impeding waste-activated sludge (WAS) fermentation. Amino sugars, such as N-acetyl-d-glucosamine (GlcNAc) polymers and sialic acid, are the non-negligible components in the EPS of aerobic granules or biofilm. However, the occurrence of amino sugars in WAS and their degradation remains unclear. Thus, amino sugars (∼6.0%) in WAS were revealed, and the genera of Lactococcus and Zoogloea were identified for the first time. Chitin was used as the substrate to enrich a chitin-degrading consortium (CDC). The COD balances for methane production ranged from 83.3 and 95.1%. Chitin was gradually converted to oligosaccharides and GlcNAc after dosing with the extracellular enzyme. After doing enriched CDC in WAS, the final methane production markedly increased to 60.4 ± 0.6 mL, reflecting an increase of ∼62%. Four model substrates of amino sugars (GlcNAc and sialic acid) and polysaccharides (cellulose and dextran) could be used by CDC. Treponema (34.3%) was identified as the core bacterium via excreting chitinases (EC 3.2.1.14) and N-acetyl-glucosaminidases (EC 3.2.1.52), especially the genetic abundance of chitinases in CDC was 2.5 times higher than that of WAS. Thus, this study provides an elegant method for the utilization of amino sugar-enriched organics.

Pharmacologically significant constituents collectively responsible for anti-sepsis action of XueBiJing, a Chinese herb-based intravenous formulation.

Sepsis, a life-threatening health issue, lacks effective medicine targeting the septic response. In China, treatment combining the intravenous herbal medicine XueBiJing with conventional procedures reduces the 28-day mortality of critically ill patients by modulating septic response. In this study, we identified the combined active constituents that are responsible for the XueBiJing's anti-sepsis action. Sepsis was induced in rats by cecal ligation and puncture (CLP). The compounds were identified based on their systemic exposure levels and anti-sepsis activities in CLP rats that were given an intravenous bolus dose of XueBiJing. Furthermore, the identified compounds in combination were assessed, by comparing with XueBiJing, for levels of primary therapeutic outcome, pharmacokinetic equivalence, and pharmacokinetic compatibility. We showed that a total of 12 XueBiJing compounds, unchanged or metabolized, circulated with significant systemic exposure in CLP rats that received XueBiJing. Among these compounds, hydroxysafflor yellow A, paeoniflorin, oxypaeoniflorin, albiflorin, senkyunolide I, and tanshinol displayed significant anti-sepsis activities, which involved regulating immune responses, inhibiting excessive inflammation, modulating hemostasis, and improving organ function. A combination of the six compounds, with the same respective doses as in XueBiJing, displayed percentage survival and systemic exposure in CLP rats similar to those by XueBiJing. Both the combination and XueBiJing showed high degrees of pharmacokinetic compatibility regarding interactions among the six active compounds and influences of other circulating XueBiJing compounds. The identification of XueBiJing's pharmacologically significant constituents supports the medicine's anti-sepsis use and provides insights into a polypharmacology-based approach to develop medicines for effective sepsis management.

ATM controls the extent of DNA end resection by eliciting sequential posttranslational modifications of CtIP.

DNA end resection is a critical step in the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR). However, the mechanisms governing the extent of resection at DSB sites undergoing homology-directed repair remain unclear. Here, we show that, upon DSB induction, the key resection factor CtIP is modified by the ubiquitin-like protein SUMO at lysine 578 in a PIAS4-dependent manner. CtIP SUMOylation occurs on damaged chromatin and requires prior hyperphosphorylation by the ATM protein kinase. SUMO-modified hyperphosphorylated CtIP is targeted by the SUMO-dependent E3 ubiquitin ligase RNF4 for polyubiquitination and subsequent degradation. Consequently, disruption of CtIP SUMOylation results in aberrant accumulation of CtIP at DSBs, which, in turn, causes uncontrolled excessive resection, defective HR, and increased cellular sensitivity to DSB-inducing agents. These findings reveal a previously unidentified regulatory mechanism that regulates CtIP activity at DSBs and thus the extent of end resection via ATM-dependent sequential posttranslational modification of CtIP.

Predicting coronary plaque progression with conventional plaque parameters and radiomics features derived from coronary CT angiography.

OBJECTIVES: To determine the value of combining conventional plaque parameters and radiomics features derived from coronary computed tomography angiography (CCTA) for predicting coronary plaque progression. MATERIALS AND METHODS: Clinical data and CCTA images of 400 patients who underwent at least two CCTA examinations between January 2009 and August 2020 were analyzed retrospectively. Diameter stenosis, total plaque volume and burden, calcified plaque volume and burden, noncalcified plaque volume and burden (NCPB), pericoronary fat attenuation index (FAI), and other conventional plaque parameters were recorded. The patients were assigned to a training cohort (n = 280) and a validation cohort (n = 120) in a 7:3 ratio using a stratified random splitting method. The area under the receiver operating characteristics curve (AUC) was used to evaluate the predictive abilities of conventional parameters (model 1), radiomics features (model 2), and their combination (model 3). RESULTS: FAI and NCPB were identified as independent risk factors for coronary plaque progression in the training cohort. Both model 2 (training cohort AUC: 0.814, p < 0.001; validation cohort AUC: 0.729, p = 0.288) and model 3 (training cohort AUC: 0.824, p < 0.001; validation cohort AUC: 0.758, p = 0.042) had better diagnostic performances in predicting plaque progression than model 1 (training cohort AUC: 0.646; validation cohort AUC: 0.654). Moreover, model 3 was slightly higher than model 2, although not statistically significant. CONCLUSIONS: The combination of conventional coronary plaque parameters and CCTA-derived radiomics features had a better ability to predict plaque progression than conventional parameters alone. CLINICAL RELEVANCE STATEMENT: The conventional coronary plaque characteristics such as noncalcified plaque burden, pericoronary fat attenuation index, and radiomics features derived from CCTA can identify plaques prone to progression, which is helpful for further clinical decision-making of coronary artery disease. KEY POINTS: • FAI and NCPB were identified as independent risk factors for predicting plaque progression. • Coronary plaque radiomics features were more advantageous than conventional parameters in predicting plaque progression. • The combination of conventional coronary plaque parameters and radiomics features could significantly improve the predictive ability of plaque progression over conventional parameters alone.

Interfacial Engineering of Ru Nanocluster-Modified TiO2 Nanotube-Assisted Regulation of Lithium Polysulfide Reactions.

The inhibition of lithium polysulfide (LiPS) diffusion and the acceleration of reaction kinetics are two major challenges for the practical application of lithium-sulfur (Li-S) batteries. Herein, through an interface engineering strategy, a multifunctional sulfur host based on Ru nanocluster-modified TiO2 nanotubes (TiO2-Ru) was designed. The TiO2-Ru interface field effect, combined with the hollow nanotube structure and the strong chemical action of TiO2, enhanced the LiPS trapping ability and inhibited the "shuttle effect". Furthermore, the high catalytic activity of Ru nanoclusters reduced the energy barrier of multistep LiPS reactions, thus speeding up the electrode kinetics. As a result, the TiO2-Ru-based composite sulfur cathode delivered excellent electrochemical performance, including an extremely low capacity loss of ∼0.015% per cycle and an increased areal capacity of ∼6.1 mAh cm-2 at 4.8 mg cm-2. This work contributes to a better sulfur cathode design from insights into morphology and phase interface engineering.

Spinal muscular atrophy with hypoplasia of the corpus callosum: a case report.

BACKGROUND: Spinal Muscular Atrophy (SMA) is a severe neuromuscular disorder due to a defect in the survival motor neuron 1 (SMN1) gene. Hypoplasia of the corpus callosum is underdevelopment or thinness of the corpus callosum. SMA and callosal hypoplasia are relatively rare, and there is limited information sharing the diagnosis and treatment for SMA patients with callosal hypoplasia. CASE DESCRIPTION: A boy with callosal hypoplasia, small penis, and small testes had been perceived with motor regression at 5 months. He was referred to the rehabilitation department and neurology department at 7 months. Physical examination showed absent deep tendon reflexes, proximal weakness and significant hypotonia. He was recommended to perform trio whole-exome sequencing (WES) and array comparative genomic hybridization (aCGH) for his complicated conditions. The subsequent nerve conduction study revealed some characteristics of motor neuron diseases. We identified a homozygous deletion in exon 7 of the SMN1 gene by multiplex ligation-dependent probe amplification and failed to find further pathogenic variations responsible for multiple malformations by trio WES and aCGH. He was diagnosed as SMA. Despite some concerns, he received the therapy of nusinersen for nearly 2 years. He gained the milestone of sitting without support, which he had never accomplished, after the seventh injection, and he continued to improve. During follow-up, there were no adverse events reported and no signs of hydrocephalus. CONCLUSIONS: Some extra features which could not belong to neuromuscular manifestation made the diagnosis and treatment of SMA more complicated.

Autophagy-related 7 proteindependent autophagy mediates resveratrol-caused upregulation of mitochondrial biogenesis and steroidogenesis in aged Leydig cell.

BACKGROUND: Mitochondrial dysfunction may contribute to decreased testosterone synthesis in aged Leydig cells. Resveratrol (RSV) as an antioxidant has been shown to exhibit multiple positive effects on mitochondrion, where steroidogenesis takes place. Whether RSV can improve steroidogenesis in aged testis is still unknown. This study investigates the effect of RSV on testosterone production during aging and corresponding changes in mitochondrial biogenesis and autophagy activity, which are closely associated with steroidogenesis. Whether ATG7, an important autophagy-related protein, functions in RSV-treated aged Leydig cells will also be explored. METHODS AND RESULTS: Two-month-old male C57BL/6 mice were fed for 16 months by customized regular diet with or without RSV as diet supplement. Leydig cell line TM3 cells were treated with D-galactose to induce senescence, followed with or without RSV treatment. Results found that RSV supplement increased testosterone production in both aged mice and D-galactose-induced senescent Leydig cells. Western blot results revealed that RSV treatment elevated levels of steroidogenic rate-limiting enzymes StAR and 3ß-HSD, as well as autophagy-related proteins LC3II, Beclin1, ATG5 and ATG7 and mitochondrial function-related proteins mtTFA and COXIV. However, after Atg7 was knocked down in senescent Leydig cells, even though RSV was added, levels of these proteins declined significantly, accompanied by decreased levels of mitochondrial transcript factors PGC-1α, mtTFA and NRF-1 and more fragmented mitochondria, demonstrating that Atg7 knockdown wrecked the protective effects of RSV on steroidogenesis in senescent Leydig cells. CONCLUSION: ATG7-dependent autophagy plays a key role in RSV-brought testosterone production increase through regulating mitochondrial biogenesis in senescent Leydig cells.

Machine learning-based prediction model of acute kidney injury in patients with acute respiratory distress syndrome.

BACKGROUND: Acute kidney injury (AKI) can make cases of acute respiratory distress syndrome (ARDS) more complex, and the combination of the two can significantly worsen the prognosis. Our objective is to utilize machine learning (ML) techniques to construct models that can promptly identify the risk of AKI in ARDS patients. METHOD: We obtained data regarding ARDS patients from the Medical Information Mart for Intensive Care III (MIMIC-III) and MIMIC-IV databases. Within the MIMIC-III dataset, we developed 11 ML prediction models. By evaluating various metrics, we visualized the importance of its features using Shapley additive explanations (SHAP). We then created a more concise model using fewer variables, and optimized it using hyperparameter optimization (HPO). The model was validated using the MIMIC-IV dataset. RESULT: A total of 928 ARDS patients without AKI were included in the analysis from the MIMIC-III dataset, and among them, 179 (19.3%) developed AKI after admission to the intensive care unit (ICU). In the MIMIC-IV dataset, there were 653 ARDS patients included in the analysis, and among them, 237 (36.3%) developed AKI. A total of 43 features were used to build the model. Among all models, eXtreme gradient boosting (XGBoost) performed the best. We used the top 10 features to build a compact model with an area under the curve (AUC) of 0.850, which improved to an AUC of 0.865 after the HPO. In extra validation set, XGBoost_HPO achieved an AUC of 0.854. The accuracy, sensitivity, specificity, positive prediction value (PPV), negative prediction value (NPV), and F1 score of the XGBoost_HPO model on the test set are 0.865, 0.813, 0.877, 0.578, 0.957 and 0.675, respectively. On extra validation set, they are 0.724, 0.789, 0.688, 0.590, 0.851, and 0.675, respectively. CONCLUSION: ML algorithms, especially XGBoost, are reliable for predicting AKI in ARDS patients. The compact model maintains excellent predictive ability, and the web-based calculator improves clinical convenience. This provides valuable guidance in identifying AKI in ARDS, leading to improved patient outcomes.

Diagnostic aid to subepidermal calcified nodule with dermoscopy and reflectance confocal microscopy: a case report.

BACKGROUND: Subepidermal calcified nodule (SCN) is a type of calcinosis cutis that usually occurs in children. The lesions in the SCN resemble those of other skin diseases, such as pilomatrixoma, molluscum contagiosum, and juvenile xanthogranuloma, leading to a high rate of misdiagnoses. Noninvasive in vivo imaging techniques, represented by dermoscopy and reflectance confocal microscopy (RCM), have dramatically accelerated skin cancer research over the past decade, and their applications have greatly expanded into other skin disorders. However, the features of an SCN in dermoscopy and RCM have yet to be reported previously. Combining these novel approaches with conventional histopathological examinations is a promising method for increasing diagnostic accuracy. CASE PRESENTATION: We report on a case of SCN of the eyelid diagnosed with the aid of dermoscopy and RCM. A 14-year-old male patient who presented with a painless yellowish-white papule on his left upper eyelid was previously diagnosed with a common wart. Unfortunately, treatment with recombinant human interferon gel was not effective. To achieve a correct diagnosis, dermoscopy and RCM were performed. The former showed closely grouped multiple yellowish-white clods surrounded by linear vessels, and the latter exhibited hyperrefractile material nests at the dermal-epidermal junction level. The alternative diagnoses were, therefore, excluded because of in vivo characterizations. Subsequent surgical excision, histological examination, and von Kossa staining were performed. Pathology showed hyperkeratosis of the epidermis, a downward-directed basal-layer expansion, and small amorphous basophilic deposits scattered throughout the papillary dermis. The von Kossa staining confirmed calcium deposits in the lesion. An SCN was then diagnosed. During the 6-month follow-up, no relapse was observed. CONCLUSIONS: Patients with SCN could benefit from dermoscopy and RCM, which help achieve an accurate diagnosis. Clinicians should consider the possibility of an SCN for an adolescent patient with painless yellowish-white papules.

Global potential, topology, and pattern selection in a noisy stabilized Kuramoto-Sivashinsky equation.

We formulate a general method to extend the decomposition of stochastic dynamics developed by Ao et al. [J. Phys. Math. Gen. 37, L25-L30 (2004)] to nonlinear partial differential equations which are nonvariational in nature and construct the global potential or Lyapunov functional for a noisy stabilized Kuramoto-Sivashinsky equation. For values of the control parameter where singly periodic stationary solutions exist, we find a topological network of a web of saddle points of stationary states interconnected by unstable eigenmodes flowing between them. With this topology, a global landscape of the steady states is found. We show how to predict the noise-selected pattern which agrees with those from stochastic simulations. Our formalism and the topology might offer an approach to explore similar systems, such as the Navier Stokes equation.

Multiple Effects of High Surface Area Hollow Nanospheres Assembled by Nickel Cobaltate Nanosheets on Soluble Lithium Polysulfides.

Inhibiting the shuttle effect of soluble polysulfides and improving slow reaction kinetics are key factors for the future development of Li-S batteries. Herein, edelweiss shaped NiCo2O4 hollow nanospheres with a high surface area were prepared by a simple template method to modify the separator to realize multiple physical constraints and strong chemical anchoring on the polysulfides. On one hand, the good electrolyte wettability of NiCo2O4 promoted the migration of Li-ions and greatly improved the dynamics. On the other hand, mesoporous NiCo2O4 nanomaterials provided many strong chemical binding sites for loading sulfur species. The hollow structure also provided a physical barrier to mitigate the sulfur species diffusion. Therefore, the modified separator realized multiple physical constraints and strong chemical anchoring on sulfur species. As a result, the sulfur cathode based on this composite separator showed significantly enhanced electrochemical performance. Even at 4 C, a high capacity of 505 mAh g-1 was obtained, and about 80.6% could be retained after 300 cycles.

Myocardial involvement characteristics by cardiac MR imaging in patients with polymyositis and dermatomyositis.

OBJECTIVE: Myocardial involvement is frequently observed in PM and DM but typically remains subclinical. This study aimed to investigate characteristics of myocardial involvement and compare differences between patients with PM and DM by cardiac MR (CMR) imaging. METHODS: From March 2017 to December 2019, a total of 17 PM and 27 DM patients were enrolled in this retrospective study. In all patients, clinical assessment and CMR examination were performed. CMR parameters, including left ventricular (LV) morphologic and functional parameters, and CMR tissue characterization imaging parameters, such as native T1, T2, extracellular volume (ECV) and late gadolinium enhancement, were analysed. RESULTS: In patients in both PM and DM groups, elevated global native T1 and ECV values were observed. Global ECV values were higher in the PM group when compared with the DM group (33.24 ± 2.97% vs 30.36 ± 4.20%; P = 0.039). Furthermore, patients in the PM and DM groups showed a different positive segment distribution of late gadolinium enhancement, native T1 and ECV, whereas the number of positive segments in PM patients was greater compared with that in DM patients. No significant differences in LV morphological and functional parameters were observed between patients in PM and DM groups, and most were in normal range. CONCLUSION: CMR tissue characterization imaging could detect early myocardial involvement in PM and DM patients without overt LV dysfunction. Furthermore, characteristics of myocardial involvement were different between PM and DM patients with more serious myocardial involvement seen in PM patients.

Background rate of low-level HCV RNA in anti-HCV confirmed-positive and minipool nucleic acid test-nonreactive blood donations.

BACKGROUND: In 2019, the Food and Drug Administration revised the requirement for further testing of anti-HCV-reactive donations testing nucleic acid (NAT)-nonreactive via routine mini-pool (MP)-NAT. Individual donation (ID)-HCV NAT was required as a supplemental test prior to a second FDA-licensed anti-HCV assay; if ID-HCV-NAT is reactive, no further testing is required. This study investigated the rate of low-level RNA in anti-HCV-reactive donation samples prior to and following the implementation of supplemental ID-HCV NAT. STUDY DESIGN/METHODS: A retrospective analysis was conducted on frozen plasma unit samples from 1161 anti-HCV confirmed-positive/HCV-NAT-nonreactive donations collected from December 2014 to January 2020. Samples were tested by multiple replicates on the Grifols Procleix Ultrio Elite (UE) assay and corresponding discriminatory HCV (dHCV) assay on the Procleix Panther System. Prospectively, the prevalence of low-level RNA in 2912 anti-HCV-reactive donations detected through routine screening from April 2020 through March 2021 was determined. RESULTS: In retrospective analyses, 10 (0.86%) of 1161 plasma samples were UE reactive, of which four (0.34%) were dHCV reactive (in all replicates of UE and dHCV). Of 2912 anti-HCV-reactive donation samples testing NAT-nonreactive via routine MP-NAT, three (0.1%; 95% CI: 0.04-0.30) were dHCV reactive; 37% of the remaining samples were reactive by a second anti-HCV assay and thus serologically confirmed. CONCLUSIONS: Retrospective and prospective analysis in comparison to earlier studies revealed that low-level HCV-RNA reactivity is decreasing over time. The very low HCV-RNA rates may be due to the widespread use of highly effective, direct-acting anti-viral treatments for those diagnosed with HCV infection.

Interventricular septum angle obtained from cardiac computed tomography for origin differentiation of outflow tract ventricular arrhythmia between left and right.

AIMS: Our objective was to explore whether the accuracy of the transitional zone index (TZI) for outflow tract ventricular arrhythmias (OT-VAs) origin is affected by cardiac rotation and the additive value of interventricular septum angle (IVSa) obtained from coronary computed tomography angiography (CCTA). METHODS: Standard 12-lead ECGs of OT-VAs with inferior axis in consecutive patients undergoing both CCTA examination and successful ablation were retrospectively analyzed. The IVSa was defined as an angle between the long axis of IVS and sagittal axis of the body from CCTA. RESULTS: 64 patients (31 men; mean age 54.2 ± 11.6 years) were enrolled. The OT-VAs exhibited right ventricular outflow tract origin in 46 (71.9%) patients and 36 (78.3%) were diagnosed correctly by TZI. The left ventricular outflow tract origin OT-VAs was observed in 18 (28.1%) patients and 16 (88.9%) were diagnosed correctly by TZI. The patients were then divided into TZI correct group (n = 52) and TZI incorrect group (n = 12). In the TZI incorrect group, 11/12 (91.7%) cases were R/S transition in lead V3 with the TZ score during premature ventricular contractions [2.8(2.5-3.4)], and the TZI between -1.5 and 0. The IVSa was significantly larger in the TZI incorrect group than correct group (52.0 ± 6.9° vs. 39.0 ± 6.1°; p < .0001). The IVSa ≥46° predicted TZI incorrect with 92% sensitivity, 94% specificity, and 94% accuracy. CONCLUSION: The IVSa is a novel cardiac rotation index that reliably improves TZI to differentiate the OT-VAs origin, especially for the OT-VAs with lead V3 R/S transition.

Nutrition status survey of type 2 and 3 spinal muscular atrophy in Chinese population.

OBJECTIVE: To evaluate the nutritional status of children with SMA types II and III in a Chinese population. METHODS: We performed a retrospective medical record review of prospectively collected data from children with SMA types II and III in a single centre. We analysed data including clinical parameters, anthropometrics, and 24-hour dietary intake records in our clinic. RESULTS: We analysed the anthropometric data from 86 children with 69 (80%) SMAII and 17 (20%) SMAIII; 47 (55%) were female, mean age was 5.22 ± 3.73 years. The WAZ of the SMAII (n = 69) and SMAIII (n = 17) were -0.48 (IQR -1.69, 0.57) vs -0.53 (IQR -1.60, 0.55), P = 0.926; the HAZ were -0.62 (IQR -1.4, 0.3) vs -0.6 (IQR -1.61, 0.4), P=0.72; the BMIZ were -0.51 (IQR -1.53, 0.99) vs -0.08 (IQR -1.625, 1.125), P = 0.537.The dietary intake of 51 children was compared to the Chinese Dietary Reference Intakes (DRIs). The actual energy intake in SMAII was similar to the DRIs, but which in SMAIII was less than the DRIs (1312.4 ± 329.5 kcal vs. 1655 ± 640.1 kcal, P = 0.028). The protein intake in SMAII and SMAIII was higher than the DRIs (55 ± 16.3 g/d vs 30.2 ± 4.6 g/d, P < 0.05; 56.8 ± 18.1 g/d vs 41.5 ± 17.5 g/d, p = 0.22), and calcium intake was lower than the recommendation (507.7 ± 177.8 mg/d vs 731.7 ± 123.4 mg/d, P < 0.05; 478.4 ± 207.4 mg/d vs 478.4 ± 207.4 mg/d, P = 0.01). Swallowing on the Neuromuscular Disease Status Scale was 7.41 ± 0.5. CONCLUSIONS: Children with SMAII and SMAIII were at risk for malnutrition and low calcium intake.

Sestrin2 protects against lethal sepsis by suppressing the pyroptosis of dendritic cells.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sestrin2 (SESN2), a highly evolutionarily conserved protein, is critically involved in the cellular response to various stresses and has been confirmed to maintain the homeostasis of the internal environment. However, the potential effects of SESN2 in regulating dendritic cells (DCs) pyroptosis in the context of sepsis and the related mechanisms are poorly characterized. In this study, we found that SESN2 was capable of decreasing gasdermin D (GSDMD)-dependent pyroptosis of splenic DCs by inhibiting endoplasmic reticulum (ER) stress (ERS)-related nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)-mediated ASC pyroptosome formation and caspase-1 (CASP-1) activation. Furthermore, SESN2 deficiency induced NLRP3/ASC/CASP-1-dependent pyroptosis and the production of proinflammatory cytokines by exacerbating the PERK-ATF4-CHOP signaling pathway, resulting in an increase in the mortality of septic mice, which was reversed by inhibiting ERS. These findings suggest that SESN2 appears to be essential for inhibiting NLRP3 inflammasome hyperactivation, reducing CASP-1-dependent pyroptosis, and improving sepsis outcomes through stabilization of the ER. The present study might have important implications for exploration of novel potential therapeutic targets for the treatment of sepsis complications.

Ultrathin Two-Dimensional Fe-Co Bimetallic Oxide Nanosheets for Separator Modification of Lithium-Sulfur Batteries.

The shuttle effect is understood to be the most significant issue that needs to be solved to improve the performance of lithium-sulfur batteries. In this study, ultrathin two-dimensional Fe-Co bimetallic oxide nanosheets were prepared using graphene as a template, which could rapidly catalyze the conversion of polysulfides and inhibit the shuttle effect. Additionally, such ultrathin nanostructures based on graphene provided sufficient active sites and fast diffusion pathways for lithium ions. Taking into account the aforementioned benefits, the ultrathin two-dimensional Fe-Co bimetallic oxide nanosheets modified separator assembled lithium-sulfur batteries delivered an incredible capacity of 1044.2 mAh g-1 at 1 C and retained an excellent reversible capacity of 859.4 mAh g-1 after 100 cycles. Even under high loading, it still achieved high area capacity and good cycle stability (92.6% capacity retention).

CCTA-derived strain analysis in detection of regional myocardial dysfunction in coronary artery disease patients with preserved left ventricular ejection fraction: A feasibility study.

OBJECTIVES: To evaluate the feasibility of using coronary computed tomography angiography (CCTA)-derived strain to detect regional myocardial dysfunction in coronary artery disease (CAD) patients with normal left ventricular ejection fraction (LVEF). METHODS: A total of 1,580 segments from 101 patients who underwent stressed CT myocardial perfusion imaging (CT-MPI) and CCTA were retrospectively enrolled in this study. The CT-derived global and segmental strain values were evaluated using the feature tracking technique. Segments with myocardial blood flow (MBF) < 125 ml/min/100 ml and 95 ml/min/100 ml were categorized as ischemic and infarcted, respectively. RESULTS: Segmental radial strain (SRS) and segmental circumferential strain (SCS) in the abnormal segments (including all segments with MBF < 125 ml/min/100 ml) were significantly lower than those in the normal segments (14.81±8.65% vs 17.17±9.13%, p < 0.001; -10.21±5.79% vs -11.86±4.52%, p < 0.001, respectively). SRS and SCS values in infarcted segments were significantly impaired compared with the ischemic segments (12.43±8.03% vs. 15.32±8.71%, p = 0.038; -7.72±5.91% vs. -10.67±5.66%, p = 0.010, respectively). The AUCs for SRS and SCS in detecting infarcted segments were 0.622 and 0.698, respectively (p < 0.05). CONCLUSIONS: It is feasible for using CCTA-derived strain parameters to detect regional myocardial dysfunction in CAD patients with preserved LVEF. Segmental radial and circumferential strain have the potential ability to distinguish myocardial ischemia from infarction, and normal from ischemic myocardium.