Frailty and risk of metabolic dysfunction-associated steatotic liver disease and other chronic liver diseases.

BACKGROUND & AIMS: Frailty is associated with multiple morbidities. However, its effect on chronic liver diseases remains largely unexplored. This study evaluated the association of frailty with the risk of incident metabolic dysfunction-associated steatotic liver disease (MASLD), cirrhosis, liver cancer, and liver-related mortality. METHODS: A total of 339,298 participants without prior liver diseases from the UK Biobank were included. Baseline frailty was assessed by using physical frailty and the frailty index, categorizing participants as nonfrail, prefrail, or frail. The primary outcome was MASLD, with secondary outcomes, including cirrhosis, liver cancer, and liver-related mortality, confirmed through hospital admission records and death registries. RESULTS: During a median follow-up of 11.6 years, 4,667 MASLD, 1,636 cirrhosis, 257 liver cancer, and 646 liver-related mortality cases were identified. After multivariable adjustment, the risk of MASLD was found to be higher in participants with prefrailty (physical frailty: HR = 1.66, 95% CI = 1.40-1.97; frailty index: HR = 2.01, 95% CI = 1.67-2.42) and frailty (physical frailty: HR = 3.32, 95% CI = 2.54-4.34; frailty index: HR = 4.54, 95% CI = 3.65-5.66) than in those with nonfrailty. Similar results were also observed for cirrhosis, liver cancer, and liver-related mortality. Additionally, the frail groups had a higher risk of MASLD, which was defined as magnetic resonance imaging-derived liver proton density fat fraction > 5%, than the nonfrail group (physical frailty: OR = 1.64, 95% CI = 1.32-2.04; frailty index: OR = 1.48, 95% CI = 1.30-1.68). CONCLUSIONS: Frailty was associated with an increased risk of chronic liver diseases. Public health strategies should target reducing chronic liver disease risk in frail individuals. IMPACT AND IMPLICATIONS: While frailty is common and associated with a poor prognosis in people with MASLD and advanced chronic liver diseases, its impact on the subsequent risk of these outcomes remains largely unexplored. Our study showed that frailty was associated with the increased risks of MASLD, cirrhosis, liver cancer, and liver-related mortality. This finding suggests that assessing frailty may help identify a high-risk population vulnerable to developing chronic liver diseases. Implementing strategies that target frailty could have major public health benefits for liver-related disease prevention.

Small vessel disease burden and prognosis of recent subcortical ischaemic stroke differ by parent artery atherosclerosis.

BACKGROUND AND PURPOSE: Parent artery atherosclerosis is an important aetiology of recent subcortical ischaemic stroke (RSIS). However, comparisons of RSIS with different degrees of parent artery atherosclerosis are lacking. METHODS: Prospectively collected data from our multicentre cohort (all were tertiary centres) of the Stroke Imaging Package Study between 2015 and 2017 were retrospectively reviewed. The patients with RSIS defined as a single clinically relevant diffusion-weighted imaging positive lesion in the territory of lenticulostriate arteries were categorized into three subgroups: (1) normal middle cerebral artery (MCA) on magnetic resonance angiography and high-resolution magnetic resonance imaging (HR-MRI); (2) low-grade MCA atherosclerosis (normal or <50% stenosis on magnetic resonance angiography and with MCA plaques on HR-MRI); (3) steno-occlusive MCA atherosclerosis (stenosis ≥50% or occlusion). The primary outcome was 90-day functional dependence (modified Rankin Scale score >2). The clinical and imaging findings were compared between subgroups. RESULTS: A total of 239 patients (median age 60.0 [52.0-67.0] years, 72% male) were enrolled, including 140 with normal MCA, 64 with low-grade MCA atherosclerosis and 35 with steno-occlusive MCA atherosclerosis. Patients with steno-occlusive MCA atherosclerosis had the largest infarct volume. Low-grade MCA atherosclerosis was independently associated with cerebral microbleeding, more severe perivascular spaces in basal ganglia and higher total cerebral small vessel disease burden. Low-grade MCA atherosclerosis was an independent determinant of 90-day functional dependence (odds ratio 3.897; 95% confidence interval 1.309-11.604). CONCLUSIONS: Our study suggested RSIS with varying severity of parent artery atherosclerosis exhibits distinctive clinical and neuroimaging characteristics, with low-grade MCA atherosclerosis associating with higher cerebral small vessel disease burden and worse prognosis.

Hospital-Treated Infectious Diseases, Infection Burden, and Risk of Lung Cancer: An Observational and Mendelian Randomization Study.

BACKGROUND: Although infections play a role in the development of lung cancer, the longitudinal association between infection and the risk of lung cancer is disputed, and data relating to pathogen types and infection sites are sparse. RESEARCH QUESTION: How do infections affect subsequent lung cancer risk, and is the impact limited to specific microbes rather than infection burden? STUDY DESIGN AND METHODS: Data on > 900 infectious diseases were gathered from the UK Biobank study. Short- and long-term effects of infections were assessed by using time-varying Cox proportional hazards models. The analysis was repeated, excluding patients with concurrent multi-pathogen infections or outcomes within the 10 years following the initial hospitalization for the index infection. A life table approach was used to estimate years of life lost from lung cancer. Infection burden was defined as the sum of the number of infection episodes over time and co-occurring infections. The genome-wide association studies used in two-sample Mendelian randomization were obtained from mostly European ancestry. RESULTS: Hospital-treated infectious disease was associated with a greater risk of lung cancer (adjusted hazard ratio [aHR], 1.79; 95% CI, 1.74-1.83). aHRs for lung cancer ranged from 1.39 to 2.82 across pathogen types. The impact of lower respiratory tract infections (LRTIs) on lung cancer was the strongest, with an aHR of 3.22 (95% CI, 2.64-3.92); the aHR for extra-LRTIs was 1.29 (95% CI, 1.16-1.44). A dose-response association was observed between infection burden and lung cancer risk across different FEV1 percent predicted (Ptrend < .001). Multiple infections led to significant life lost from lung cancer at the age of 50 years. Mendelian randomization analysis reaffirmed the causal association. INTERPRETATION: Both observational and genetic analyses suggest that infectious diseases could increase the risk of lung cancer. The dual perspective on the LRTIs and extra-LRTIs impacts may inform lung cancer prevention strategies.

Quantitative Assessment of Acute Intracranial Clot and Collaterals on High-Resolution Magnetic Resonance Imaging.

INTRODUCTION: There has been an increasing demand for imaging methods that provide a comprehensive evaluation of intracranial clot and collateral circulation, which are helpful for clinical decision-making and predicting functional outcomes. We aimed to quantitatively evaluate acute intracranial clot burden and collaterals on high-resolution magnetic resonance imaging (HR-MRI). METHODS: We analyzed acute ischemic stroke patients with internal carotid artery or middle cerebral artery occlusion in a prospective multicenter study. The clot burden was scored on a scale of 0-10 based on the clot location on HR-MRI. The collateral score was assigned on a scale of 0-3 using the minimum intensity projection from HR-MRI. Uni- and multivariable logistic regression analyses were performed to assess their correlation with clinical outcome (modified Rankin Scale >2 at 90 days). Thresholds were defined to dichotomize into low- and high-score groups, and predictive performances were assessed for clinical and radiologic outcomes. RESULTS: Ninety-nine patients (mean age of 60.77 ± 11.54 years) were included in the analysis. The interobserver correlation was 0.89 (95% CI: 0.77-0.95) for the clot burden score and 0.78 (95% CI: 0.53-0.90) for the collateral score. Multivariable logistic regression analysis demonstrated that the collateral score (odds ratio: 0.41, 95% CI: 0.19-0.90) was significantly associated with clinical outcomes. A better functional outcome was observed in the group with clot burden scores greater than 7 (p = 0.011). A smaller final infarct size and a higher diffusion-weighted imaging-based Alberta Stroke Program Early Computed Tomography Score were observed in the group with collateral scores greater than 1 (all p < 0.05). CONCLUSIONS: HR-MRI offers a new tool for quantitative assessment of clot burden and collaterals simultaneously in future clinical practices and research endeavors.

Small but bright: origin of the enhanced luminescence of ultrasmall ZnGa2O4:Cr3+ in mesoporous silica nanoparticles.

Chromium(III)-doped zinc gallate (CZGO) is one of the representative persistent luminescent phosphors emitting in the near-infrared (NIR) region. The emission wavelength it covers falls in the tissue-transparent window, making CZGO a promising optical probe for various biomedical applications. The PersL mechanism dictates that such a phenomenon is only profound in large crystals, so the preparation of CZGO with sizes small enough for biological applications while maintaining its luminescence remains a challenging task. Recent attempts to use mesoporous silica nanoparticles (MSN) as a template for growing nanosized CZGO have been successful. MSN is also a well-studied drug carrier, and incorporating CZGO in MSN further expands its potential in imaging-guided therapeutics. Despite the interest, it is unclear of how the addition of MSN would affect the luminescence properties of CZGO. In this work, we observed that forming a CZGO@MSN nanocomposite could enhance the luminescence intensity and extend the PersL lifetime of CZGO. X-ray absorption fine structure (XAFS) analysis was conducted to investigate the local structure of Zn2+, and an interaction between Zn2+ in CZGO and the MSN matrix was identified.

The relationship between ischemic penumbra progression and the oxygen content of cortex microcirculation in acute ischemic stroke.

The precise oxygen content thresholds of ischemic deep parenchymal (OCIDP) and that in cortical microcirculation (OCCM), which leads to ischemic penumbra converting into the infarcted core, remain uncertain. This study employed an invasive fiber-optic oxygen meter and a newly developed oxygen-responsive probe called RuA3-Cy5-rtPA (RC-rtPA) based on recombinant tissue-type plasminogen activator (rtPA) to examine the oxygen content thresholds. A mouse model of middle cerebral artery occlusion was generated and animals were randomly divided into a sham, 24-h reperfusion after 3-h ischemia (IR 3-h), and IR 6-h groups, all of which were sacrificed following reperfusion. Stroke severity was evaluated based on the infarction area, neurological symptoms, microcirculation perfusion, and microemboli in microcirculation. OCIDP was characterized based on its extent and distribution, whereas OCCM was measured using RC-rtPA. During ischemia, stroke severity escalation manifested as increasing infarction area, severe neurologic symptoms, and poorer microcirculation perfusion with more microthrombi depositions. OCIDP presented rapid decline following artery occlusion along with a gradual increase in the hypoxic area. Within 3 â€‹h following ischemia induction, the ischemic tissue that experienced hypoxia could be rescued, and this reversibility would disappear after 6 â€‹h. Within 6 â€‹h, OCCM continued to decrease. A significant decrease in oxygen content in cortical venules and cortical parenchyma was observed. These findings assist in establishing the extent of the ischemic penumbra at the microcirculation level and offer a foundation for assessing the ischemic penumbra that could respond positively to reperfusion therapy beyond the typical time window.

Harmonizing Between Chemical Functionality and Surface Area of Porous Organic Polymeric Nanotraps for Tuning Carbon Dioxide Capture.

The energy sector has demonstrated significant enthusiasm for investigating post-combustion CO2 capture, storage, and separation. However, the practical application of current porous adsorbents is impeded by challenges related to cost competitiveness, stability, and scalability. Intregation of heteroatoms in the porous organic polymers (POPs) dispense it more susceptible for CO2 adsorption to attenuate green house gases. In this regard, two hydroxy rich hypercrosslinked POPs, namely Ph/Tt-POP have been developed by one-pot condensation polymerization using a facile synthetic strategy. The high surface areas of both the Ph/Tt-POP (1057 and 893 m2g-1, respectively), and the heteroatom functionality in the POP framework instigated us to explore our material for CO2 adsorption study. The CO2 uptake capacities in Ph/Tt-POP are found to be 2.45 and 2.2 mmol g-1, at 273 K respectively. Further, in-situ static 13C NMR experiment shows that CO2 molecules in Tt-POP appear to be less mobile than those in Ph-POP which probably due to the presence of triazine functional groups along with high abundant -OH groups in the Tt-POP framework. An in-depth study of the CO2 adsorption mechanism by density functional theory (DFT) calculations also shows that CO2 adsorption at the cages formed by two benzyl rings represents the most stable interaction and CO2 molecule is more favorably adsorbed on the Ph-POP with the more negative interaction energies values compared to that of Tt-POP. Further, Non-covalent interaction (NCI) plot reveals that CO2 molecules adsorb more on the Ph-POP than Tt-POP, which can be explain by hydrogen bond formation in case of Tt-POP repeating units turning aside CO2 molecule to interact with the Ph component. Overall, our present study reflects the comprising effects of surface area of the solid adsorbents as well as their functionality can be beneficial for developing efficient hypercrosslinked porous polymers as solid CO2 adsorbent.

Understanding Cu(i) local environments in MOFs via63/65Cu NMR spectroscopy.

The field of metal-organic frameworks (MOFs) includes a vast number of hybrid organic and inorganic porous materials with wide-ranging applications. In particular, the Cu(i) ion exhibits rich coordination chemistry in MOFs and can exist in two-, three-, and four-coordinate environments, which gives rise to many structural motifs and potential applications. Direct characterization of the structurally and chemically important Cu(i) local environments is essential for understanding the sources of specific MOF properties. For the first time, 63/65Cu solid-state NMR has been used to investigate a variety of Cu(i) sites and local coordination geometries in Cu MOFs. This approach is a sensitive probe of the local Cu environment, particularly when combined with density functional theory calculations. A wide range of structurally-dependent 63/65Cu NMR parameters have been observed, including 65Cu quadrupolar coupling constants ranging from 18.8 to 74.8 MHz. Using the data from this and prior studies, a correlation between Cu quadrupolar coupling constants, Cu coordination number, and local Cu coordination geometry has been established. Links between DFT-calculated and experimental Cu NMR parameters are also presented. Several case studies illustrate the feasibility of 63/65Cu NMR for investigating and resolving inequivalent Cu sites, monitoring MOF phase changes, interrogating the Cu oxidation number, and characterizing the product of a MOF chemical reaction involving Cu(ii) reduction to Cu(i). A convenient avenue to acquire accurate 65Cu NMR spectra and NMR parameters from Cu(i) MOFs at a widely accessible magnetic field of 9.4 T is described, with a demonstrated practical application for tracking Cu(i) coordination evolution during MOF anion exchange. This work showcases the power of 63/65Cu solid-state NMR spectroscopy and DFT calculations for molecular-level characterization of Cu(i) centers in MOFs, along with the potential of this protocol for investigating a wide variety of MOF structural changes and processes important for practical applications. This approach has broad applications for examining Cu(i) centers in other weight-dilute systems.

Pressure Tuning and Sn Particle Size Optimization for Enhanced Performance in PbSnF4-Based All-Solid-State Fluoride Ion Batteries.

All-solid-state fluoride ion batteries (ASSFIBs) show remarkable potential as energy storage devices due to their low cost, superior safety, and high energy density. However, the poor ionic conductivity of F- conductor, large volume expansion, and the lack of a suitable anode inhibit their development. In this work, PbSnF4 solid electrolytes in different phases (ß- and γ-PbSnF4) are successfully synthesized and characterized. The ASSFIBs composed of ß-PbSnF4 electrolytes, a BiF3 cathode, and micrometer/nanometer size (µ-/n-) Sn anodes, exhibit substantial capacities. Compared to the µ-Sn anode, the n-Sn anode with nanostructure exhibits superior battery performance in the BiF3/ß-PbSnF4/Sn battery. The optimized battery delivers a high initial discharge capacity of 181.3 mAh g-1 at 8 mA g-1 and can be reversibly cycled at 40 mA g-1 with a high discharge capacity of over 100.0 mAh g-1 after 120 cycles at room temperature. Additionally, it displays high discharge capacities over 90.0 mAh g-1 with excellent cyclability over 100 cycles under -20 °C. Detailed characterization has confirmed that reducing Sn particle size and boosting external pressure are crucial for achieving good defluorination/fluorination behaviors in the Sn anode. These findings pave the way to designing ASSFIBs with high capacities and superior cyclability under different operating temperatures.

Layout analysis of the RCEP international airline network based on hub identification using improved contribution matrix.

The signing of the Regional Comprehensive Economic Partnership agreement brings new opportunities for the development of international air transportation. Faced with fierce competition, it is worth studying how hub airports should enhance competitiveness, and how low-cost carriers and full-service carriers should optimize the RCEP international airline network layout for better development. Aiming at providing suggestions for the development of hub airports, low-cost and full-service carriers in the RCEP international airline network, this paper identifies the hub airports, analyzes the layout of the RCEP international airline network, and the multi-layered characteristics based on an improved contribution matrix using data from 2010 to 2019 collected from the Official Airline Guide (OAG). This method comprehensively considers attributes of hub airports and the multi-layered characteristics of the airports and routes. The layout analysis indicates that the RCEP international transportation market presents a more open environment for competition and cooperation where base carriers are often the biggest supporters of hub construction. The multi-layered characteristics analysis reveals that low-cost carriers contribute more towards opening up new RCEP routes than full-service carriers. It is advised that carriers newly entering the RCEP international aviation transportation market and low-cost carriers dedicate to establishing new routes around their hub airports to monopolize this market and enhance their market share, whilst full-service carriers consolidate existing routes and increase route density to achieve economic benefits.

Association of hospital-treated infectious diseases and infection burden with cardiovascular diseases and life expectancy.

BACKGROUND: The association of a broad spectrum of infectious diseases with cardiovascular outcomes remains unclear. OBJECTIVES: We aim to provide the cardiovascular risk profiles associated with a wide range of infectious diseases and explore the extent to which infections reduce life expectancy. METHODS: We ascertained exposure to 900+ infectious diseases before cardiovascular disease (CVD) onset in 453,102 participants from the UK Biobank study. Time-varying Cox proportional hazard models were used. Life table was used to estimate the life expectancy of individuals aged ≥50 with different levels of infection burden (defined as the number of infection episodes over time and the number of co-occurring infections). RESULTS: Infectious diseases were associated with a greater risk of CVD events (adjusted HR [aHR] 1.79 [95% confidence interval {CI} 1.74-1.83]). For type-specific analysis, bacterial infection with sepsis had the strongest risk of CVD events [aHR 4.76 (4.35-5.20)]. For site-specific analysis, heart and circulation infections posed the greatest risk of CVD events [aHR 4.95 (95% CI 3.77-6.50)], whereas noncardiac infections also showed excess risk [1.77 (1.72-1.81)]. Synergistic interactions were observed between infections and genetic risk score. A dose-response relationship was found between infection burden and CVD risks (p-trend <0.001). Infection burden >1 led to a CVD-related life loss at age 50 by 9.3 years [95% CI 8.6-10.3]) for men and 6.6 years [5.5-7.8] for women. CONCLUSIONS: The magnitude of the infection-CVD association showed specificity in sex, pathogen type, infection burden, and infection site. High genetic risk and infection synergistically increased the CVD risk.

Analysis of Preimplantation and Clinical Outcomes of Two Cases by Oxford Nanopore Sequencing.

It is challenging to distinguish embryos with a balanced translocation karyotype from a normal karyotype by existing conventional genetic testing methods. However, in germ-cell gamete generation, chromosome exchange and separation through cell meiosis form a different proportion of unbalanced gametes. Adverse birth events may occur, such as repeated miscarriages and fetal birth defects. In this study, the exact breakpoints of structural variation (SV) from two balanced translocation carrier families by using Nanopore long reads sequencing technology were obtained, and haplotype analysis and Sanger verified the accuracy of the detection results, confirming the application value of the Nanopore sequencing technology in the detection of balanced translocation before embryo implantation. Nanopore long-read sequencing was performed to find the precise breakpoint of chromosome-balanced translocation carriers. The breakpoints were subsequently verified by designing primers across the breakpoints and Sanger sequencing. Haplotype linkage analysis of SNPs which can be linked by a read block of families around the breakpoint regions was followed. After frozen (-thawed) embryo transfer (FET), prenatal cytogenetic analysis of amniotic fluid cells confirmed the predicted karyotypes from the transferred embryos. The presence of breakpoints was detected in three embryos of patient 1. No breakpoints were detected in either embryo of patient 2. One balanced translocated embryo from patient 1 and one normal euploid embryo from patient 2 were transplanted back into the patients, and amniotic fluid cells were analyzed for the karyotype of fetuses. The results were entirely consistent with the fetal karyotype. And through late follow-up, both patients successfully had a live birth fetus. The breakpoint location of the balanced chromosome translocation can be accurately found by Nanopore sequencing. The haplotype of carriers can be successfully constructed by Nanopore and sanger sequencing confirmed that the results were accurate. This is very advantageous for preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR) detection in the families without proband.

Geographic differences in pharmacotherapy patterns and outcomes of acute ischemic stroke in China.

BACKGROUND: Vast economic and healthcare status discrepancies exist among regions in China, contributing to different treatment patterns. This study was aimed to investigate the current status of pharmacotherapy for acute ischemic stroke (AIS) and outcomes in China and explore the geographic variation in stroke care. METHODS: This study was a multicenter prospective registry study, which collected the data of patients with AIS from 80 hospitals in 46 cities in 2015-2017 across China. Poor functional outcome defined as a modified Rankin Scale score of 3-6 was assessed at 3 and 12 months. Multivariate logistic regression was used. RESULTS: Among 9973 eligible patients, the number of receiving intravenous thrombolysis (IVT), antiplatelet agents, anticoagulants, statin and human urinary kallidinogenase was 429 (4.3%), 9363 (93.9%), 1063 (10.7%), 6828 (74.7%) and 5112 (51.2%), respectively. Multivariable analysis showed IVT use in northeastern was significantly more frequent than in eastern region (OR = 3.17, 95% CI, 2.53-3.99), while the antiplatelets agents use were less frequent (OR = 0.46, 95%CI: 0.38-0.57). The proportions of poor outcomes at 3 and 12 months were 20.7% and 15.8%, respectively. Multivariate analysis showed AIS patients from northeastern and central region had significantly lower risk of poor outcome at month 3 and 12 than those from eastern region (all P < 0.05). CONCLUSIONS: There was a low IVT use and a high antiplatelet agent and statin use for AIS in China. The pharmacotherapy and prognosis of AIS had variation by geographic region. TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov (NCT02470624).

Amorphous Oxyhalide Matters for Achieving Lithium Superionic Conduction.

The recently surged halide-based solid electrolytes (SEs) are great candidates for high-performance all-solid-state batteries (ASSBs), due to their decent ionic conductivity, wide electrochemical stability window, and good compatibility with high-voltage oxide cathodes. In contrast to the crystalline phases in halide SEs, amorphous components are rarely understood but play an important role in Li-ion conduction. Here, we reveal that the presence of amorphous component is common in halide-based SEs that are prepared via mechanochemical method. The fast Li-ion migration is found to be associated with the local chemistry of the amorphous proportion. Taking Zr-based halide SEs as an example, the amorphization process can be regulated by incorporating O, resulting in the formation of corner-sharing Zr-O/Cl polyhedrons. This structural configuration has been confirmed through X-ray absorption spectroscopy, pair distribution function analyses, and Reverse Monte Carlo modeling. The unique structure significantly reduces the energy barriers for Li-ion transport. As a result, an enhanced ionic conductivity of (1.35 ± 0.07) × 10-3 S cm-1 at 25 °C can be achieved for amorphous Li3ZrCl4O1.5. In addition to the improved ionic conductivity, amorphization of Zr-based halide SEs via incorporation of O leads to good mechanical deformability and promising electrochemical performance. These findings provide deep insights into the rational design of desirable halide SEs for high-performance ASSBs.

Cubic Iodide Lix YI3+x Superionic Conductors through Defect Manipulation for All-Solid-State Li Batteries.

Halide solid electrolytes (SEs) have attracted significant attention due to their competitive ionic conductivity and good electrochemical stability. Among typical halide SEs (chlorides, bromides, and iodides), substantial efforts have been dedicated to chlorides or bromides, with iodide SEs receiving less attention. Nevertheless, compared with chlorides or bromides, iodides have both a softer Li sublattice and lower reduction limit, which enable iodides to possess potentially high ionic conductivity and intrinsic anti-reduction stability, respectively. Herein, we report a new series of iodide SEs: Lix YI3+x (x=2, 3, 4, or 9). Through synchrotron X-ray/neutron diffraction characterizations and theoretical calculations, we revealed that the Lix YI3+x SEs belong to the high-symmetry cubic structure, and can accommodate abundant vacancies. By manipulating the defects in the iodide structure, balanced Li-ion concentration and generated vacancies enables an optimized ionic conductivity of 1.04 × 10-3  S cm-1 at 25 °C for Li4 YI7 . Additionally, the promising Li-metal compatibility of Li4 YI7 is demonstrated via electrochemical characterizations (particularly all-solid-state Li-S batteries) combined with interface molecular dynamics simulations. Our study on iodide SEs provides deep insights into the relation between high-symmetry halide structures and ionic conduction, which can inspire future efforts to revitalize halide SEs.

A Dual Anion Chemistry-Based Superionic Glass Enabling Long-Cycling All-Solid-State Sodium-Ion Batteries.

Glassy Na-ion solid-state electrolytes (GNSSEs) are an important group of amorphous SSEs. However, the insufficient ionic conductivity of state-of-the-art GNSSEs at room temperature lessens their promise in the development of all-solid-state Na-ion batteries (ASSNIBs) with high energy density and improved safety. Here we report the discovery of a new sodium superionic glass, 0.5Na2 O2 -TaCl5 (NTOC), based on dual-anion sublattice of oxychlorides. The unique local structures with abundant bridging and non-bridging oxygen atoms contributes to a highly disordered Na-ion distribution as well as low Na+ migration barrier within NTOC, enabling an ultrahigh ionic conductivity of 4.62 mS cm-1 at 25 °C (more than 20 times higher than those of previously reported GNSSEs). Moreover, the excellent formability of glassy NTOC electrolyte and its high electrochemical oxidative stability ensure a favourable electrolyte-electrode interface, contributing to superior cycling stability of ASSNIBs for over 500 cycles at room temperature. The discovery of glassy NTOC electrolyte would reignite research enthusiasm in superionic glassy SSEs based on multi-anion chemistry.

Aquaporin 4 Mediates the Effect of Iron Overload on Hydrocephalus After Intraventricular Hemorrhage.

BACKGROUND: Iron overload plays an important role in hydrocephalus development following intraventricular hemorrhage (IVH). Aquaporin 4 (AQP4) participates in the balance of cerebrospinal fluid secretion and absorption. The current study investigated the role of AQP4 in the formation of hydrocephalus caused by iron overload after IVH. METHODS: There were three parts to this study. First, Sprague-Dawley rats received an intraventricular injection of 100 µl autologous blood or saline control. Second, rats had IVH and were treated with deferoxamine (DFX), an iron chelator, or vehicle. Third, rats had IVH and were treated with 2-(nicotinamide)-1,3,4-thiadiazole (TGN-020), a specific AQP4 inhibitor, or vehicle. Rats underwent T2-weighted and T2* gradient-echo magnetic resonance imaging to assess lateral ventricular volume and intraventricular iron deposition at 7, 14, and 28 days after intraventricular injection and were then euthanized. Real-time quantitative polymerase chain reaction, western blot analysis, and immunofluorescence analyses were conducted on the rat brains to evaluate the expression of AQP4 at different time points. Hematoxylin and eosin-stained brain sections were obtained to assess the ventricular wall damage on day 28. RESULTS: Intraventricular injection of autologous blood caused a significant ventricular dilatation, iron deposition, and ventricular wall damage. There was increased AQP4 mRNA and protein expression in the periventricular tissue in IVH rats through day 7 to day 28. The DFX treatment group had a lower lateral ventricular volume and less intraventricular iron deposition and ventricular wall damage than the vehicle-treated group after IVH. The expression of AQP4 protein in periventricular tissue was also inhibited by DFX on days 14 and 28 after IVH. The use of TGN-020 attenuated hydrocephalus development after IVH and inhibited the expression of AQP4 protein in the periventricular tissue between day 14 and day 28 without a significant effect on intraventricular iron deposition or ventricular wall damage. CONCLUSIONS: AQP4 located in the periventricular area mediated the effect of iron overload on hydrocephalus after IVH.

The predictive, preventive, and personalized medicine of insomnia: gut microbiota and inflammation.

Background: The human gut microbiota (GM) has been recognized as a significant factor in the development of insomnia, primarily through inflammatory pathways, making it a promising target for therapeutic interventions. Considering the principles of primary prediction, targeted prevention, and personalized treatment medicine (PPPM), identifying specific gut microbiota associated with insomnia and exploring the underlying mechanisms comprehensively are crucial steps towards achieving primary prediction, targeted prevention, and personalized treatment of insomnia. Working hypothesis and methodology: We hypothesized that alterations in the composition of specific GM could induce insomnia through an inflammatory response, which postulates the existence of a GM-inflammation-insomnia pathway. Mendelian randomization (MR) analyses were employed to examine this pathway and explore the mediative effects of inflammation. We utilized genetic proxies representing GM, insomnia, and inflammatory indicators (including 41 circulating cytokines and C-reactive protein (CRP)), specifically identified from European ancestry. The primary method used to identify insomnia-related GM and examine the medicative effect of inflammation was the inverse variance weighted method, supplemented by the MR-Egger and weighted median methods. Our findings have the potential to identify individuals at risk of insomnia through screening for GM imbalances, leading to the development of targeted prevention and personalized treatment strategies for the condition. Results: Nine genera and three circulating cytokines were identified to be associated with insomnia; only the associations of Clostridium (innocuum group) and ß-NGF on insomnia remained significant after the FDR test, OR = 1.08 (95% CI = 1.04-1.12, P = 1.45 × 10-4, q = 0.02) and OR = 1.06 (95% CI = 1.02-1.10, P = 1.06 × 10-3, q = 0.04), respectively. CRP was associated with an increased risk of insomnia, OR = 1.05 (95% CI = 1.01-1.10, P = 6.42 × 10-3). CRP mediated the association of Coprococcus 1, Holdemania, and Rikenellaceae (RC9gut group) with insomnia. No heterogeneity or pleiotropy were detected. Conclusions: Our study highlights the role of specific GM alterations in the development of insomnia and provides insights into the mediating effects of inflammation. Targeting these specific GM alterations presents a promising avenue for advancing the transition from reactive medicine to PPPM in managing insomnia, potentially leading to significant clinical benefits. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00345-1.

Autologous non-invasively derived stem cells mitochondria transfer shows therapeutic advantages in human embryo quality rescue.

BACKGROUND: The decline in the quantity and quality of mitochondria are closely associated with infertility, particularly in advanced maternal age. Transferring autologous mitochondria into the oocytes of infertile females represents an innovative and viable strategy for treating infertility, with no concerns regarding ethical considerations. As the donor cells of mitochondria, stem cells have biological advantages but research and evidence in this area are quite scarce. METHODS: To screen out suitable human autologous ooplasmic mitochondrial donor cells, we performed comprehensive assessment of mitochondrial physiology, function and metabolic capacity on a varity of autologous adipose, marrow, and urine-derived mesenchymal stromal cells (ADSC, BMSC and USC) and ovarian germline granulosa cells (GC). Further, to explore the biosafety, effect and mechanism of stem cell-derived mitochondria transfer on human early embryo development, randomized in-vitro basic studies were performed in both of the young and aged oocytes from infertile females. RESULTS: Compared with other types of mesenchymal stromal cells, USC demonstrated a non-fused spherical mitochondrial morphology and low oxidative stress status which resembled the oocyte stage. Moreover, USC mitochondrial content, activity and function were all higher than other cell types and less affected by age, and it also exhibited a biphasic metabolic pattern similar to the pre-implantation stage of embryonic development. After the biosafety identification of the USC mitochondrial genome, early embryos after USC mitochondrial transfer showed improvements in mitochondrial content, activity, and cytoplasmic Ca2+ levels. Further, aging embryos also showed improvements in embryonic morphological indicators, euploidy rates, and oxidative stress status. CONCLUSION: Autologous non-invasively derived USC mitochondria transfer may be an effective strategy to improve embryonic development and metabolism, especially in infertile females with advanced age or repeated pregnancy failure. It provides evidence and possibility for the autologous treatment of infertile females without invasive and ethical concerns.

Enhancing CO2 adsorption capacity of ZIF-8 by synergetic effect of high pressure and temperature.

Metal-organic frameworks (MOFs) and zeolitic imidazolate frameworks (ZIFs) are promising porous materials for adsorption and storage of greenhouse gases, especially CO2. In this study, guided by the CO2 phase diagram, we explore the adsorption behavior of solid CO2 loaded with ZIF-8 framework by heating the sample under high pressures, resulting in a drastic improvement in the CO2 uptake. The behavior of CO2 under simultaneous high temperature (T) and pressure (P) conditions is directly monitored by in situ FTIR spectroscopy. The remarkable enhancement in CO2 adsorption capability observed can be attributed to the synergetic effect of high T and P: high temperature greatly enhances the transport property of solid CO2 by facilitating its diffusion into the framework; high pressure effectively modifies the pore size and shape via changing the linker orientation and creating new adsorption sites within ZIF-8. Our study thus provides important new insights into the tunability and enhancement of CO2 adsorptive capability in MOFs/ZIFs using pressure and temperature combined as a synergetic approach.