Macrophage biomimetic nanoparticle-targeted functional extracellular vesicle micro-RNAs revealed via multiomics analysis alleviate sepsis-induced acute lung injury.

Patients who suffer from sepsis typically experience acute lung injury (ALI). Extracellular vesicles (EVs) contain miRNAs, which are potentially involved in ALI. However, strategies to screen more effective EV-miRNAs as therapeutic targets are yet to be elucidated. In this study, functional EV-miRNAs were identified based on multiomics analysis of single-cell RNA sequencing of targeted organs and serum EV (sEV) miRNA profiles in patients with sepsis. The proportions of neutrophils and macrophages were increased significantly in the lungs of mice receiving sEVs from patients with sepsis compared with healthy controls. Macrophages released more EVs than neutrophils. MiR-125a-5p delivery by sEVs to lung macrophages inhibited Tnfaip3, while miR-221-3p delivery to lung neutrophils inhibited Fos. Macrophage membrane nanoparticles (MM NPs) loaded with an miR-125a-5p inhibitor or miR-221-3p mimic attenuated the response to lipopolysaccharide (LPS)-induced ALI. Transcriptome profiling revealed that EVs derived from LPS-stimulated bone marrow-derived macrophages (BMDMs) induced oxidative stress in neutrophils. Blocking toll-like receptor, CXCR2, or TNFα signaling in neutrophils attenuated the oxidative stress induced by LPS-stimulated BMDM-EVs. This study presents a novel method to screen functional EV-miRNAs and highlights the pivotal role of macrophage-derived EVs in ALI. MM NPs, as delivery systems of key sEV-miRNA mimics or inhibitors, alleviated cellular responses observed in sepsis-induced ALI. This strategy can be used to reduce septic organ damage, particularly lung damage, by targeting EVs.

Classification, detection, and segmentation performance of image-based AI in intracranial aneurysm: a systematic review.

BACKGROUND: The detection and management of intracranial aneurysms (IAs) are vital to prevent life-threatening complications like subarachnoid hemorrhage (SAH). Artificial Intelligence (AI) can analyze medical images, like CTA or MRA, spotting nuances possibly overlooked by humans. Early detection facilitates timely interventions and improved outcomes. Moreover, AI algorithms offer quantitative data on aneurysm attributes, aiding in long-term monitoring and assessing rupture risks. METHODS: We screened four databases (PubMed, Web of Science, IEEE and Scopus) for studies using artificial intelligence algorithms to identify IA. Based on algorithmic methodologies, we categorized them into classification, segmentation, detection and combined, and then their merits and shortcomings are compared. Subsequently, we elucidate potential challenges that contemporary algorithms might encounter within real-world clinical diagnostic contexts. Then we outline prospective research trajectories and underscore key concerns in this evolving field. RESULTS: Forty-seven studies of IA recognition based on AI were included based on search and screening criteria. The retrospective results represent that current studies can identify IA in different modal images and predict their risk of rupture and blockage. In clinical diagnosis, AI can effectively improve the diagnostic accuracy of IA and reduce missed detection and false positives. CONCLUSIONS: The AI algorithm can detect unobtrusive IA more accurately in communicating arteries and cavernous sinus arteries to avoid further expansion. In addition, analyzing aneurysm rupture and blockage before and after surgery can help doctors plan treatment and reduce the uncertainties in the treatment process.

Optimizing zoning for ecological management in alpine region by combining ecosystem service supply and demand with ecosystem resilience.

In order to enhance ecosystem stability and promote sustainable regional ecological, social, and economic development, it is crucial to explore the coupling relationship between ecosystem service supply and demand and the resilience of ecosystem, so as to propose scientific ecological management zones and strategies. Taking the vulnerable alpine ecosystem in Gannan Tibetan Autonomous Prefecture (Gannan Prefecture) as the study area, this paper comprehensively utilized multi-source data, grid analysis, ecosystem service supply and demand estimation model, and coupled coordination model to analyze the spatio-temporal differentiation and coordination pattern of ecosystem service supply and demand in the study area from 2000 to 2020. With the assistance of the Analytic Hierarchy Process (AHP), the ecosystem resilience index system was constructed to evaluate the regional ecological resilience. The results reveal the following: (1) In the past 20 years, the ecosystem service supply and resilience in Gannan Prefecture showed a fluctuating upward trend, and the demand continued to grow steadily. Their spatial differentiation were obvious, but the pattern remained stable. (2) There was a moderate incoordination indicated by the average coordination degree of the supply and demand coupling of ecosystem services, which rangeed between 0.3 and 0.4. (3) Gannan Prefecture was split into three ecological management zones, considering the spatial distribution of ecosystem service supply and demand, as well as resilience. Through system function monitoring and other measures, the ecological conservation zone will rely on its high resilience to support the restoration and self-sufficiency of the system, ensuring the stability and well-being of the ecosystem. The primary objectives of general protected zone includes environmental preservation, strict regulations, and the prevention of human intervention. To enhance their ecological background, key restoration zone must intensify the implementation of ecological restoration initiatives. To address the needs of the locals, strategies such as ecological compensation, optimizing the land use structure, and fostering the growth of environmentally friendly companies can be implemented simultaneously.

Macrophagic Extracellular Vesicle CXCL2 Recruits and Activates the Neutrophil CXCR2/PKC/NOX4 Axis in Sepsis.

Sepsis is a life-threatening organ dysfunction caused by a dysfunctional host response to infection. Neutrophils play a protective role by releasing antibacterial proteins or by phagocytizing bacteria. However, excess neutrophils can induce tissue damage. Recently, a novel intercellular communication pathway involving extracellular vesicles (EVs) has garnered considerable attention. However, whether EVs secreted by macrophages mediate neutrophil recruitment to infected sites has yet to be studied. In this study, we assessed the chemotactic effect of EVs isolated from mouse Raw264.7 macrophages on mouse neutrophils and found that CXCL2 was highly expressed in these EVs. By regulating CXCL2 in Raw264.7 macrophages, we found that CXCL2 on macrophage EVs recruited neutrophils in vitro and in vivo. The CXCL2 EVs activated the CXCR2/PKC/NOX4 pathway and induced tissue damage. This study provides information regarding the mechanisms underlying neutrophil recruitment to tissues and proposes innovative strategies and targets for the treatment of sepsis.

Rapid, sensitive, and high-throughput quantification of broad serological ceramides by using isotope dilution liquid chromatography-negative ion electrospray tandem mass spectrometry.

Ceramides are important intermediates in the metabolism of sphingolipids. High-throughput liquid chromatography-mass spectrometry has been used extensively for monitoring the levels of serological ceramides, but is still limited by inadequate coverage or lack of sensitivity. Herein, a rapid, sensitive, and high-throughput isotope dilution liquid chromatography-negative ion electrospray tandem mass spectrometry (IDLC-nESI-MS/MS) method was developed and verified for accurate quantification of 41 ceramides, involving ceramides with C16-20 sphingosine, dihydro-ceramide, and dehydro-ceramide. This method was validated with excellent linearity (R2 > 0.99) and good recovery in the range of 90-110%. Intra- and inter-day imprecision were below 5.57% and 7.83% respectively. The improved high-throughput quantitative method developed in this study may aid in the accurate characterization of ceramides for understanding ceramide biology and application in disease diagnosis.

NOD-like Receptor Signaling Pathway in Gastrointestinal Inflammatory Diseases and Cancers.

Nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) are intracellular proteins with a central role in innate and adaptive immunity. As a member of pattern recognition receptors (PRRs), NLRs sense specific pathogen-associated molecular patterns, trigger numerous signaling pathways and lead to the secretion of various cytokines. In recent years, cumulative studies have revealed the significant impacts of NLRs in gastrointestinal (GI) inflammatory diseases and cancers. Deciphering the role and molecular mechanism of the NLR signaling pathways may provide new opportunities for the development of therapeutic strategies related to GI inflammatory diseases and GI cancers. This review presents the structures and signaling pathways of NLRs, summarizes the recent advances regarding NLR signaling in GI inflammatory diseases and GI cancers and describes comprehensive therapeutic strategies based on this signaling pathway.

Predictive role of blood eosinophils in adult varicella patients.

The study aimed to explore the relationship between eosinophils and the prognosis of varicella in adults. We retrospectively reviewed the medical records of patients who were hospitalised in The Fifth People's Hospital of Suzhou with a diagnosis of adult varicella during the period between 1 January 2012 and 31 December 2020. Of the 359 patients, 228 (63.51%) had eosinopenia. The proportion of patients with mild type disease was significantly lower in the eosinopenia group than that in the non-eosinopenia group (50.44% vs. 65.65%, P = 0.006). The proportion of the patients with common type disease was significantly higher in the eosinopenia group than that in the non-eosinopenia group (39.47% vs. 28.24%, P = 0.039). The proportion of the patients with severe type disease was higher in the eosinopenia group, although the difference did not reach statistical significance (10.09% vs. 6.11%, P = 0.243). The rates of high fever (47.81% vs. 32.82%, P = 0.008; relative risk (RR) 1.296, 95% confidence interval (CI) 1.091-1.540), headache (43.42% vs. 22.14%, P < 0.001; RR 1.415, 95% CI 1.233-1.623), anorexia (53.51% vs. 35.88%, P = 0.001; RR 1.367, 95% CI 1.129-1.655) and complications (82.89% vs. 64.12%, P < 0.001; RR 2.106, 95% CI 1.460-3.038) were also significantly higher in the eosinopenia group. Among the complications, the liver injury and skin infection were more serious in the eosinopenia group. The disease course was significantly longer in the eosinopenia group than that in the non-eosinopenia group (9.43 ± 1.89 days vs. 8.73 ± 1.25 days, P < 0.001). The improvement rate of liver injury in the recovery period was lower in the eosinopenia group than that in the non-eosinopenia group (35.38% vs. 50%, P = 0.012). The study found that adult varicella patients with eosinopenia had a more serious condition, a higher morbidity of complications and a slower recovery. Blood eosinophils can be used as a new predictor of the severity of adult varicella.

CPVA: a web-based metabolomic tool for chromatographic peak visualization and annotation.

MOTIVATION: Liquid chromatography-mass spectrometry-based non-targeted metabolomics is routinely performed to qualitatively and quantitatively analyze a tremendous amount of metabolite signals in complex biological samples. However, false-positive peaks in the datasets are commonly detected as metabolite signals by using many popular software, resulting in non-reliable measurement. RESULTS: To reduce false-positive calling, we developed an interactive web tool, termed CPVA, for visualization and accurate annotation of the detected peaks in non-targeted metabolomics data. We used a chromatogram-centric strategy to unfold the characteristics of chromatographic peaks through visualization of peak morphology metrics, with additional functions to annotate adducts, isotopes and contaminants. CPVA is a free, user-friendly tool to help users to identify peak background noises and contaminants, resulting in decrease of false-positive or redundant peak calling, thereby improving the data quality of non-targeted metabolomics studies. AVAILABILITY AND IMPLEMENTATION: The CPVA is freely available at http://cpva.eastus.cloudapp.azure.com. Source code and installation instructions are available on GitHub: https://github.com/13479776/cpva. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Serum metabolomic and lipidomic profiling identifies diagnostic biomarkers for seropositive and seronegative rheumatoid arthritis patients.

BACKGROUND: Diagnosing seronegative rheumatoid arthritis (RA) can be challenging due to complex diagnostic criteria. We sought to discover diagnostic biomarkers for seronegative RA cases by studying metabolomic and lipidomic changes in RA patient serum. METHODS: We performed comprehensive metabolomic and lipidomic profiling in serum of 225 RA patients and 100 normal controls. These samples were divided into a discovery set (n = 243) and a validation set (n = 82). A machine-learning-based multivariate classification model was constructed using distinctive metabolites and lipids signals. RESULTS: Twenty-six metabolites and lipids were identified from the discovery cohort to construct a RA diagnosis model. The model was subsequently tested on a validation set and achieved accuracy of 90.2%, with sensitivity of 89.7% and specificity of 90.6%. Both seropositive and seronegative patients were identified using this model. A co-occurrence network using serum omics profiles was built and parsed into six modules, showing significant association between the inflammation and immune activity markers and aberrant metabolism of energy metabolism, lipids metabolism and amino acid metabolism. Acyl carnitines (20:3), aspartyl-phenylalanine, pipecolic acid, phosphatidylethanolamine PE (18:1) and lysophosphatidylethanolamine LPE (20:3) were positively correlated with the RA disease activity, while histidine and phosphatidic acid PA (28:0) were negatively correlated with the RA disease activity. CONCLUSIONS: A panel of 26 serum markers were selected from omics profiles to build a machine-learning-based prediction model that could aid in diagnosing seronegative RA patients. Potential markers were also identified in stratifying RA cases based on disease activity.

A Chinese family with Noonan syndrome caused by a heterozygous variant in LZTR1: a case report and literature review.

BACKGROUND: Noonan syndrome is an inherited disease involving multiple systems. More than 15 related genes have been discovered, among which LZTR1 was discovered recently. However, the pathogenesis and inheritance pattern of LZTR1 in Noonan syndrome have not yet been elucidated. CASE PRESENTATION: We herein describe a family with LZTR1-related Noonan syndrome. In our study, the proband, sister, mother, maternal aunt and grandmother and female cousin showed the typical or atypical features of Noonan syndrome. Only 3 patients underwent the whole-exome sequencing analysis and results showed that the proband as well as her sister inherited the same heterozygous LZTR1 variant (c.1149 + 1G > T) from their affected mother. Moreover, the proband accompanied by growth hormone deficiency without other associated variants. CONCLUSION: In a Chinese family with Noonan syndrome, we find that the c.1149 + 1G > T variant in LZTR1 gene shows a different autosomal dominant inheritance from previous reports, which changes our understanding of its inheritance and improves our understanding of Noonan syndrome.

The influence of risk perception for COVID-19 pandemic on posttraumatic stress disorder in healthcare workers: A survey from four designated hospitals.

The aim of current study was to investigate risk perception of COVID-19 pandemic, sleep quality and time change of leisure activity and their correlations with posttraumatic stress disorder (PTSD) in healthcare workers (HCWs) from four designated hospitals in China. Medical staffs (n = 317) from three designated hospitals in Guangdong Province and one designated hospital in Guangxi Province were surveyed on their demographic information, sleep quality and time change of leisure activity, risk perception of pandemic and PTSD symptoms (by using PTSD checklist for DSM-5 (PCL-5)). Hierarchical regression and structural equation model (SEM) were used to examine the correlated factors of PTSD. The prevalence of high level of PTSD symptoms (PCL-5 > =33, a probable diagnosis of PTSD) was 10.7%. Regression analysis found that risk perception (dread: ß = 0.142, p < 0.01; familiarity: ß = 0.203, p < 0.01), sleep quality (ß = 0.250, p < 0.001), time change of leisure activity (ß = -0.179, p < 0.01), were independently correlated with PTSD severity, which was further confirmed by SEM. Locations of COVID-19-related hazards were significant different in cognitive map of risk perception between groups with high and low levels of PTSD symptoms. Risk perception of COVID-19 pandemic influenced PTSD symptoms in HCWs. Adequate time for leisure activity and good sleep quality protected some HCWs against PTSD symptoms under the influence of pandemic. More researches were warranted to understand the path from pre-factors of risk perception to its psychological consequences among HCWs.

Chiral Magnetism and High-Temperature Skyrmions in B20-Ordered Co-Si.

Magnets with chiral crystal structures and helical spin structures have recently attracted much attention as potential spin-electronics materials, but their relatively low magnetic-ordering temperatures are a disadvantage. While cobalt has long been recognized as an element that promotes high-temperature magnetic ordering, most Co-rich alloys are achiral and exhibit collinear rather than helimagnetic order. Crystallographically, the B20-ordered compound CoSi is an exception due to its chiral structure, but it does not exhibit any kind of magnetic order. Here, we use nonequilibrium processing to produce B20-ordered Co_{1+x}Si_{1-x} with a maximum Co solubility of x=0.043. Above a critical excess-Co content (x_{c}=0.028), the alloys are magnetically ordered, and for x=0.043, a critical temperature T_{c}=328 K is obtained, the highest among all B20-type magnets. The crystal structure of the alloy supports spin spirals caused by Dzyaloshinskii-Moriya interactions, and from magnetic measurements we estimate that the spirals have a periodicity of about 17 nm. Our density-functional calculations explain the combination of high magnetic-ordering temperature and short periodicity in terms of a quantum phase transition where excess-cobalt spins are coupled through the host matrix.

Successful pregnancy after prenatal diagnosis by NGS for a carrier of complex chromosome rearrangements.

BACKGROUND: The study is aimed to provide prediction for fertility risk in the setting of assisted reproduction for a woman with complex chromosomal rearrangements (CCRs). METHODS: We implemented a robust approach, which combined whole-genome low-coverage mate-pair sequencing (WGL-MPS), junction-spanning PCR and preimplantation genetic testing for aneuploidy (PGT-A) method to provide accurate chromosome breakpoint junctional sequences in the embryo selection process in the setting of assisted reproduction for a couple with recurrent abortions due to CCRs. RESULT: WGL-MPS was applied to a female carrying CCRs which consisted of 9 breakpoints and 1 cryptic deletion related to fertility risks. Sequencing data provided crucial information for designing junction-spanning PCR and PGT-A process, which was performed on the 11 embryos cultivated. One embryo was considered qualified for transplanting, which carried the exact same CCRs as the female carrier, whose phenotype was normal. The amniotic fluid was also investigated by WGL-MPS and karyotyping at 19 weeks' gestation, which verified the results that the baby carried the same CCRs. A healthy baby was born at 39 weeks' gestation by vaginal delivery. CONCLUSION(S): Our study illustrates the WGL-MPS approach combining with junction-spanning PCR and PGT-A is a powerful and practical method in the setting of assisted reproduction for couples with recurrent miscarriage due to chromosomal abnormalities, especially CCRs carriers.

Fine Characterization of the Macromolecular Structure of Huainan Coal Using XRD, FTIR, 13C-CP/MAS NMR, SEM, and AFM Techniques.

Research on the composition and structure of coal is the most important and complex basic research in the coal chemistry field. Various methods have been used to study the structure of coal from different perspectives. However, due to the complexity of coal and the limitations of research methods, research on the macromolecular structure of coal still lacks systematicness. Huainan coalfield is located in eastern China and is the largest coal production and processing base in the region. In this study, conventional proximate analysis and ultimate analysis, as well as advanced instrumental analysis methods, such as Fourier transform infrared spectroscopy (FITR), X-ray diffraction (XRD), 13C-CP/MAS NMR, and other methods (SEM and AFM), were used to analyze the molecular structure of Huainan coal (HNC) and the distribution characteristics of oxygen in different oxygen-containing functional groups (OCFGs) in an in-depth manner. On the basis of SEM observation, it could be concluded that the high-resolution morphology of HNC's surface contains pores and fractures of different sizes. The loose arrangement pattern of HNC's molecular structure could be seen from 3D AFM images. The XRD patterns show that the condensation degree of HNC's aromatic ring is low, and the orientation degree of carbon network lamellae is poor. The calculated ratio of the diameter of aromatic ring lamellae to their stacking height (La/Lc = 1.05) and the effective stacking number of aromatic nuclei (Nave = 7.3) show that the molecular space structure of HNC is a cube formed of seven stacked aromatic lamellae. The FTIR spectra fitting results reveal that the aliphatic chains in HNC's molecular structure are mainly methyne and methylene. Oxygen is mainly -O-, followed by -C=O, and contains a small amount of -OH, the ratio of which is about 8:1:2. The molar fraction of binding elements has the approximate molecular structure C100H76O9N of organic matter in HNC. The results of the 13C NMR experiments show that the form of aromatic carbon atoms in HNC's structure (the average structural size X_b of aromatic nucleus = 0.16) is mainly naphthalene with a condensation degree of 2, and the rest are aromatic rings composed of benzene rings and heteroatoms. In addition, HNC is relatively rich in ≡CH and -CH2- structures.

Protective effect of the glucagon-like peptide-1 analogue liraglutide on carbon tetrachloride-induced acute liver injury in mice.

Acute liver injury seriously endangers human health. Liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, has antioxidative effects in addition to being widely used in the treatment of type 2 diabetes and was reported to ameliorate liver diseases. The aim of this study was to evaluate the hepatoprotective effects of liraglutide on carbon tetrachloride (CCl4)-induced acute liver injury in mice and to investigate the mechanisms involved in this protective effect. Male BALB/c mice were pre-treated with liraglutide (200 µg/kg/day) by hypodermic injection for 3 days before a 0.1% (v/v) CCl4 (10 ml/kg, dissolved in olive oil) intraperitoneal injection, or post-treated with liraglutide once immediately after a CCl4 intraperitoneal injection. The experimental data showed that liraglutide treatment significantly decreased the serum ALT and AST levels and ameliorated the liver histopathological changes induced by CCl4. In addition, liraglutide pre-treatment dramatically increased the number of proliferating cell nuclear antigen (PCNA)-positive hepatocytes and significantly reduced hepatocyte apoptosis after CCl4 treatment. As a consequence, liraglutide pre-treatment significantly prevented CCl4-induced malondialdehyde (MDA) production and increased the activity of the antioxidant superoxide dismutase (SOD) enzyme. In addition, liraglutide pre-treatment significantly ameliorated mitochondrial respiratory functions and ultrastructural features. Furthermore, liraglutide pre-treatment enhances the activation of the NRF2/HO-1 signaling pathway. In summary, liraglutide protects against CCl4-induced acute liver injury by protecting mitochondrial functions and inhibiting oxidative stress, which may partly involve the activation of NRF2/HO-1 signaling pathway.

Fecal microbiota transplantation alleviates myocardial damage in myocarditis by restoring the microbiota composition.

Myocarditis can be caused by several infectious and noninfectious causes. Treatment for myocarditis is still a difficult task in clinical practice. The gut microbiota is related to cardiovascular diseases such as atherosclerosis and hypertension. However, little is known about the role of the gut microbiota in myocarditis. In our study, we tested the hypothesis that gut dysbiosis is associated with myocarditis. We focused on whether fecal microbiota transplantation (FMT) can be used as an effective treatment for myocarditis. We used an experimental autoimmune myocarditis (EAM) mouse model. Fecal samples were isolated from the control and EAM groups for bacterial genome analysis. We observed an increase in microbial richness and diversity in the myocarditis mice. These changes were accompanied by an increased Firmicutes/Bacteroidetes ratio. We also evaluated the efficacy of FMT for the treatment of myocarditis. EAM mouse guts were repopulated with fecal contents from an untreated male mouse donor. We found that myocardial injury was improved by diminished inflammatory infiltration, showing that IFN-γ gene expression in the heart tissue and CD4+IFN-γ+ cells in the spleen were decreased after FMT in EAM mice. We also found that FMT was able to rebalance the gut microbiota by restoring the Bacteroidetes population and reshaping the microbiota composition. Myocarditis is associated with gut microbiota dysbiosis and characterized by an increased F/B ratio. FMT treatment can rebalance the gut microbiota and attenuate myocarditis. Thus, FMT may be a potential therapeutic strategy for the treatment of myocarditis.

Screening of triploid with low-coverage whole-genome sequencing by a single-nucleotide polymorphism-based test in miscarriage tissue.

PURPOSE: To establish a single-nucleotide polymorphism-based analysis (SBA) method to identify triploidy in the miscarriage tissue by using low-coverage whole-genome sequencing (LC-WGS). METHODS: The method was established by fitting a quadratic curve model by counting the distribution of three heterozygous mutation content intervals. The triploid test result was mainly determined by the opening direction and the axis of symmetry of the quadratic curve, and Z test between the same batch samples was also used for auxiliary judgment. RESULTS: Two hundred thirteen diploid samples and 8 triploid samples were used for establishment of the analytical method and 203 unknown samples were used for blind testing. In the blind testing, we found 2 cases positive for triploidy. After chromosome microarray analysis (CMA) and mass spectrometry verification, we found that both samples were true positives. We randomly selected 5 samples from the negative samples for mass spectrometry verification, and the results showed that these samples were all true negatives. CONCLUSIONS: Our method achieved accurate detection of triploidy in the miscarriage tissue and has the potential to detect more chromosomal abnormality types such as uniparental disomy (UPD) using a single LC-WGS approach.

A Multi-Ion Strategy towards Rechargeable Sodium-Ion Full Batteries with High Working Voltage and Rate Capability.

Sodium-ion batteries (SIBs) are a promising alternative for the large-scale energy storage owing to the natural abundance of sodium. However, the practical application of SIBs is still hindered by the low working voltage, poor rate performance, and insufficient cycling stability. A sodium-ion based full battery using a multi-ion design is now presented. The optimized full batteries delivered a high working voltage of about 4.0 V, which is the best result of reported sodium-ion full batteries. Moreover, this multi-ion battery exhibited good rate performance up to 30 C and a high capacity retention of 95 % over 500 cycles at 5 C. Although the electrochemical performance of this multi-ion battery may be further enhanced via optimizing electrolyte and electrode materials for example, the results presented clearly indicate the feasibility of this multi-ion strategy to improve the electrochemical performance of SIBs for possible energy storage applications.

On a framework of data assimilation for hyperparameter estimation of spiking neuronal networks.

When handling real-world data modeled by a complex network dynamical system, the number of the parameters is often much more than the size of the data. Therefore, in many cases, it is impossible to estimate these parameters and the exact value of each parameter is frequently less interesting than the distribution of the parameters. In this paper, we aim to estimate the distribution of the parameters in the mesoscopic neuronal network model from the macroscopic experimental data, for example, the BOLD (blood oxygen level dependent) signal. Herein, we assume that the parameters of the neurons and synapses are inhomogeneous but independently and identically distributed from certain distributions with unknown hyperparameters. Thus, we estimate these hyperparameters of the distributions of the parameters, instead of estimating the parameters themselves. We formulate this problem under the framework of data assimilation and hierarchical Bayesian method and present an efficient method named Hierarchical Data Assimilation (HDA) to conduct the statistical inference on the neuronal network model with the BOLD signal data simulated by the hemodynamic model. We consider the Leaky Integral-Fire (LIF) neuronal networks with four synapses and show that the proposed algorithm can estimate the BOLD signals and the hyperparameters with high preciseness. In addition, we discuss the influence on the performance of the algorithm configuration and the LIF network model setup.

Coexisting RET/PTC and TERT Promoter Mutation Predict Poor Prognosis but Effective RET and MEK Targets in Thyroid Cancer.

PURPOSE: To investigate the role of coexisting RET/PTC rearrangement and TERT promoter mutation in the prognosis and therapeutic targeting in papillary thyroid cancer (PTC). METHODS: A total of 669 PTC patients with complete clinical follow-up and genetic data were pooled from thyroid cancer datasets TCGA, MSK MetTropism, and MSK-IMPACT, from whom 163 patients (112 women and 47 men, 4 unknown) with wild-type BRAF/RAS were identified, with median age (IQR) of 46.00 (33.00, 61.00) years and median follow-up time (IQR) of 16.13 (8.09, 27.91) months for comparative genotype cohort analysis of mortality. RESULTS: There was a significant concurrence index between RET/PTC and TERT promoter mutations, being 2.040 (95% CI 1.110-3.747, P = 0.023). Mortality occurred in 5/100 (5%) patients harboring neither mutation, 2/18 (11.1%) patients harboring TERT promoter mutation alone, 0/31 (0%) patients harboring RET/PTC alone, and 7/14 (50%) patients harboring both genetic alterations, corresponding to HRs (95% CI) of 1 (Reference), 2.469 (0.405-14.02), 3.296e-09 (0-inf), and 9.019 (2.635-30.87), respectively, which remained essentially unchanged after adjustment for patient race, sex, and age. Similar results were observed with BRAF/RAS and TERT promoter mutations. Mechanistically, RET/PTC used the MAP kinase pathway to upregulate the mutated TERT, but not the wild-type TERT, and, correspondingly, targeting RET and MEK could suppress mutated TERT but not the wild-type TERT. CONCLUSION: Coexisting RET/PTC and TERT promoter mutation identify PTC as a unique clinical entity with high mortality, providing new implications for genetic-based prognostication and potential therapeutic targeting of RET and MEK guided by RET/PTC and TERT status.