Chloroflexus aurantiacus acetyl-CoA carboxylase evolves fused biotin carboxylase and biotin carboxyl carrier protein to complete carboxylation activity.

Acetyl-CoA carboxylases (ACCs) convert acetyl-CoA to malonyl-CoA, a key step in fatty acid biosynthesis and autotrophic carbon fixation pathways. Three functionally distinct components, biotin carboxylase (BC), biotin carboxyl carrier protein (BCCP), and carboxyltransferase (CT), are either separated or partially fused in different combinations, forming heteromeric ACCs. However, an ACC with fused BC-BCCP and separate CT has not been identified, leaving its catalytic mechanism unclear. Here, we identify two BC isoforms (BC1 and BC2) from Chloroflexus aurantiacus, a filamentous anoxygenic phototroph that employs 3-hydroxypropionate (3-HP) bi-cycle rather than Calvin cycle for autotrophic carbon fixation. We reveal that BC1 possesses fused BC and BCCP domains, where BCCP could be biotinylated by E. coli or C. aurantiacus BirA on Lys553 residue. Crystal structures of BC1 and BC2 at 3.2 Å and 3.0 Å resolutions, respectively, further reveal a tetramer of two BC1-BC homodimers, and a BC2 homodimer, all exhibiting similar BC architectures. The two BC1-BC homodimers are connected by an eight-stranded ß-barrel of the partially resolved BCCP domain. Disruption of ß-barrel results in dissociation of the tetramer into dimers in solution and decreased biotin carboxylase activity. Biotinylation of the BCCP domain further promotes BC1 and CTß-CTα interactions to form an enzymatically active ACC, which converts acetyl-CoA to malonyl-CoA in vitro and produces 3-HP via co-expression with a recombinant malonyl-CoA reductase in E. coli cells. This study revealed a heteromeric ACC that evolves fused BC-BCCP but separate CTα and CTß to complete ACC activity.IMPORTANCEAcetyl-CoA carboxylase (ACC) catalyzes the rate-limiting step in fatty acid biosynthesis and autotrophic carbon fixation pathways across a wide range of organisms, making them attractive targets for drug discovery against various infections and diseases. Although structural studies on homomeric ACCs, which consist of a single protein with three subunits, have revealed the "swing domain model" where the biotin carboxyl carrier protein (BCCP) domain translocates between biotin carboxylase (BC) and carboxyltransferase (CT) active sites to facilitate the reaction, our understanding of the subunit composition and catalytic mechanism in heteromeric ACCs remains limited. Here, we identify a novel ACC from an ancient anoxygenic photosynthetic bacterium Chloroflexus aurantiacus, it evolves fused BC and BCCP domain, but separate CT components to form an enzymatically active ACC, which converts acetyl-CoA to malonyl-CoA in vitro and produces 3-hydroxypropionate (3-HP) via co-expression with recombinant malonyl-CoA reductase in E. coli cells. These findings expand the diversity and molecular evolution of heteromeric ACCs and provide a structural basis for potential applications in 3-HP biosynthesis.

Reutilization of Silicon-Cutting Waste via Constructing Multilayer Si@SiO2@C Composites as Anode Materials for Li-Ion Batteries.

The rapid development of the photovoltaic industry has also brought some economic losses and environmental problems due to the waste generated during silicon ingot cutting. This study introduces an effective and facile method to reutilize silicon-cutting waste by constructing a multilayer Si@SiO2@C composite for Li-ion batteries via two-step annealing. The double-layer structure of the resultant composite alleviates the severe volume changes of silicon effectively, and the surrounding slightly graphitic carbon, known for its high conductivity and mechanical strength, tightly envelops the silicon nanoflakes, facilitates ion and electron transport and maintains electrode structural integrity throughout repeated charge/discharge cycles. With an optimization of the carbon content, the initial coulombic efficiency (ICE) was improved from 53% to 84%. The refined Si@SiO2@C anode exhibits outstanding cycling stability (711.4 mAh g-1 after 500 cycles) and rate performance (973.5 mAh g-1 at 2 C). This research presents a direct and cost-efficient strategy for transforming photovoltaic silicon-cutting waste into high-energy-density lithium-ion battery (LIB) anode materials.

Love-hate relationship between hepatitis B virus and type 2 diabetes: a Mendelian randomization study.

Objective: The impact of hepatitis B virus (HBV) on the risk of type 2 diabetes (T2D) remains a controversial topic. This study aims to analyze the causal relationship between HBV and T2D using Mendelian randomization (MR). Methods: Single nucleotide polymorphisms on chronic hepatitis B (CHB), liver fibrosis, liver cirrhosis, and T2D were obtained from BioBank Japan Project, European Bioinformatics Institute, and FinnGen. Mendelian randomization was utilized to evaluate exposure-outcome causality. Inverse variance weighted was used as the primary method for MR analysis. To assess horizontal pleiotropy and heterogeneity, we conducted MR-Egger intercept analysis and Cochran's Q test, and the robustness of the MR analysis results was evaluated through leave-one-out sensitivity analysis. Results: MR analysis revealed that CHB was associated with a decreased genetic susceptibility to T2D (OR, 0.975; 95% CI, 0.962-0.989; p < 0.001) while liver cirrhosis (OR, 1.021; 95% CI, 1.007-1.036; p = 0.004) as well as liver cirrhosis and liver fibrosis (OR, 1.015; 95% CI, 1.002-1.028; p = 0.020) were associated with an increased genetic susceptibility to T2D. MR-Egger intercept showed no horizontal pleiotropy (p > 0.05). Cochran's Q showed no heterogeneity (p > 0.05). Leave-one-out sensitivity analysis showed that the results were robust. Conclusion: CHB has the potential to act as a protective factor for T2D, but its effectiveness is constrained by viral load and disease stage. This protective effect diminishes or disappears as viral load decreases, and it transforms into a risk factor with the progression to liver fibrosis and cirrhosis.

High-Energy Symmetric Li-Ion Battery Enabled by Binder-Free FeOF-MXene Heterostructure with Doubly Matched Capacity and Kinetics.

Fluorides are viewed as promising conversion-type Li-ion battery cathodes to meet the desired high energy density. FeOF is a typical member of conversion-type fluorides, but its major drawback is sluggish kinetics upon deep discharge. Herein, a heterostructured FeOF-MXene composite (FeOF-MX) is demonstrated to overcome this limitation. The rationally designed FeOF-MX electrode features a microsphere morphology consisting of closely packed FeOF nanoparticles, providing fast transport pathways for lithium ions while a continuous wrapping network of MXene nanosheets ensures unobstructed electron transport, thus enabling high-rate lithium storage with enhanced pseudocapacitive contribution. In/ex situ characterization techniques and theoretical calculations, both reveal that the lithium storage mechanism in FeOF arises from a hybrid intercalation-conversion process, and strong interfacial interactions between FeOF and MXene promote Li-ion adsorption and migration. Remarkably, through demarcating the conversion-type reaction with a controlled potential window, a symmetric full battery with prelithiated FeOF-MX as both cathode and anode is fabricated, achieving a high energy density of 185.5 Wh kg-1 and impressive capacity retention of 88.9% after 3000 cycles at 1 A g-1. This work showcases an effective route toward high-performance MXene engineered fluoride-based electrodes and provides new insights into constructing symmetric batteries yet with high-energy/power densities.

Impacts of active mobility on individual health mediated by physical activities.

Active mobility, encompassing walking and cycling for transportation, is a potential solution to health issues arising from inadequate physical activity in modern society. However, the extent of active mobility's impact on individual physical activity levels, and its association with health as mediated by physical activities, is not fully quantified. This study aims to clarify the direct relationship between active mobility usage and individual health, as well as the indirect relationship mediated by physical activity, with a focus on varying levels of physical activity intensity. Utilizing data from the 2017 U.S. National Household Travel Survey (NHTS), we employed Poisson regression to predict active mobility usage based on socio-demographic and household socio-economic characteristics. A Structural Equation Model (SEM) was then used to investigate the direct and indirect effects of active mobility on individual health, mediated by physical activity. We further segmented individuals according to their intensity of physical activity to examine how such effect differs between different levels of physical activity. The study demonstrates that active mobility usage positively correlates with both the amount and intensity of physical activity. The effect of active mobility on individual health includes a direct positive effect (29% for intensity, 67.7% for amount) and an indirect effect mediated by physical activity (71% for intensity, 32.3% for amount). Notably, the mediation effect of active mobility on health is more substantial in the context of vigorous physical activities compared to light or moderate activities. Our findings reveal a significant positive influence of active mobility on individual health, encompassing both direct and indirect effects mediated by physical activities. These results quantitatively underscore the health benefits of active mobility and suggest the importance of promoting active mobility as a strategy to improve public health.

Risk of intracranial hemorrhage in patients using anticoagulant therapy for atrial fibrillation after cerebral microbleeds combined with acute ischemic stroke: a meta-analysis.

Objective: To evaluate intracerebral hemorrhage (ICH) risk in patients with ischemic stroke (IS) and cerebral microbleeds (CMBs) undergoing anticoagulation therapy for non-valvular atrial fibrillation (AF). Methods: We conducted a comprehensive search across multiple databases, including Embase, PubMed, Cochrane, UpToDate, Scopus, WOS, and SinoMed. The search covered observational literature published from each database inception until February 1, 2023. We analyzed the prevalence of CMBs during the follow-up period, compared future ICH risk between patients with and without baseline CMBs (CMBs presence/absence, ≧5 CMBs), and examined factors influencing ICH occurrence in patients with CMBs. Also studied recurrent stroke during anticoagulation therapy, the risk of future ICH when white matter hyperintensity (WMH) and CMBs coexist, and the effects of anticoagulants vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) on future ICH. Results: We included 7 articles involving 5,134 participants. The incidence of CMBs was 24%; baseline CMBs were associated with an increased ICH risk compared to patients without CMBs. ICH-risk was more significant in patients with baseline ≥5 CMBs. After anticoagulant therapy, ICH risk was higher than that of recurrent IS. The risk of future ICH was significantly increased with anticoagulant VKAs compared with NOAC. Conclusion: Anticoagulant therapy for ischemic stroke patients with non-valvular AF and CMBs increases future ICH risk. Discontinuing anticoagulation due to ICH risk should be avoided. NOACs are safe and effective for patients with CMBs and IS.

Oncolytic adenovirus encoding apolipoprotein A1 suppresses metastasis of triple-negative breast cancer in mice.

BACKGROUND: Dysregulation of cholesterol metabolism is associated with the metastasis of triple-negative breast cancer (TNBC). Apolipoprotein A1 (ApoA1) is widely recognized for its pivotal role in regulating cholesterol efflux and maintaining cellular cholesterol homeostasis. However, further exploration is needed to determine whether it inhibits TNBC metastasis by affecting cholesterol metabolism. Additionally, it is necessary to investigate whether ApoA1-based oncolytic virus therapy can be used to treat TNBC. METHODS: In vitro experiments and mouse breast cancer models were utilized to evaluate the molecular mechanism of ApoA1 in regulating cholesterol efflux and inhibiting breast cancer progression and metastasis. The gene encoding ApoA1 was inserted into the adenovirus genome to construct a recombinant adenovirus (ADV-ApoA1). Subsequently, the efficacy of ADV-ApoA1 in inhibiting the growth and metastasis of TNBC was evaluated in several mouse models, including orthotopic breast cancer, spontaneous breast cancer, and human xenografts. In addition, a comprehensive safety assessment of Syrian hamsters and rhesus monkeys injected with oncolytic adenovirus was conducted. RESULTS: This study found that dysregulation of cholesterol homeostasis is critical for the progression and metastasis of TNBC. In a mouse orthotopic model of TNBC, a high-cholesterol diet promoted lung and liver metastasis, which was associated with keratin 14 (KRT14), a protein responsible for TNBC metastasis. Furthermore, studies have shown that ApoA1, a cholesterol reverse transporter, inhibits TNBC metastasis by regulating the cholesterol/IKBKB/FOXO3a/KRT14 axis. Moreover, ADV-ApoA1 was found to promote cholesterol efflux, inhibit tumor growth, reduce lung metastasis, and prolonged the survival of mice with TNBC. Importantly, high doses of ADV-ApoA1 administered intravenously and subcutaneously were well tolerated in rhesus monkeys and Syrian hamsters. CONCLUSIONS: This study provides a promising oncolytic virus treatment strategy for TNBC based on targeting dysregulated cholesterol metabolism. It also establishes a basis for subsequent clinical trials of ADV-ApoA1 in the treatment of TNBC.

RP105 Attenuates Ischemia/Reperfusion-Induced Oxidative Stress in the Myocardium via Activation of the Lyn/Syk/STAT3 Signaling Pathway.

Although our previous studies have established the crucial role of RP105 in myocardial ischemia/reperfusion injury (MI/RI), its involvement in regulating oxidative stress induced by MI/RI remains unclear. To investigate this, we conducted experiments using a rat model of ischemia/reperfusion (I/R) injury. Adenovirus carrying RP105 was injected apically at multiple points, and after 72 h, the left anterior descending coronary artery was ligated for 30 min followed by 2 h of reperfusion. In vitro experiments were performed on H9C2 cells, which were transfected with recombinant adenoviral vectors for 48 h, subjected to 4 h of hypoxia, and then reoxygenated for 2 h. We measured oxidative stress markers, including superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, as well as malondialdehyde (MDA) concentration, using a microplate reader. The fluorescence intensity of reactive oxygen species (ROS) in myocardial tissue was measured using a DHE probe. We also investigated the upstream and downstream components of the signal transducer and activator of transcription 3 (STAT3). Upregulation of RP105 increased SOD and GSH-Px activities, reduced MDA concentration, and inhibited ROS production in response to I/R injury in vivo and hypoxia reoxygenation (H/R) stimulation in vitro. The overexpression of RP105 led to a decrease in the myocardial enzyme LDH in serum and cell culture supernatant, as well as a reduction in infarct size. Additionally, left ventricular fraction (LVEF) and fractional shortening (LVFS) were improved in the RP105 overexpression group compared to the control. Upregulation of RP105 promoted the expression of Lyn and Syk and further activated STAT phosphorylation, which was blocked by PP2 (a Lyn inhibitor). Our findings suggest that RP105 can inhibit MI/RI-induced oxidative stress by activating STAT3 via the Lyn/Syk signaling pathway.

Aquatic photolysis of high-risk fluorinated liquid crystal monomers: Kinetics, toxicity evaluation, and mechanisms.

Despite the frequent detection of fluorinated liquid-crystal monomers (FLCMs) in the environment, the level of understanding of their fate, toxicity, and transformation remains insufficient. Herein, we investigated the degradation kinetics and mechanism of an FLCM (4-cyano-3-fluorophenyl 4-ethylbenzoate, CEB-F) under ultraviolet (UV) photolysis in aquatic environment. Our findings demonstrated that the UV photolysis of CEB-F followed first-order kinetics. Photodegradation products were identified using liquid chromatography with mass spectrometry, and detailed reaction pathways were proposed. It is postulated that through the attack of reactive oxygen species, hydroxylation, and CO/C-F bond cleavage, CEB-F gradually degraded into small molecular compounds, releasing fluorine ions. Acute immobilization tests with Daphnia magna (D. magna) revealed significant acute toxicity of CEB-F, with LC50 values ranging from 1.023 to 0.0536 µM over 24 to 96 h, emphasizing the potential high risk of FLCMs in aquatic ecosystems if inadvertently discharged. Interestingly, we found that the toxicity of CEB-F photolysis reaction solutions was effectively reduced. Through catalase and acetylcholinesterase activities analysis along with molecular docking simulation, we proposed differences in the underlying toxicity mechanisms of CEB-F and its photolysis products to D. magna. These findings highlight the potential harmful effects of FLCMs on aquatic ecosystems and enrich our understanding of the photolysis behavior of FLCMs.

Design of heterostructured hydrangea-like FeS2/MoS2 encapsulated in nitrogen-doped carbon as high-performance anode for potassium-ion capacitors.

The means of structural hybridization such as heterojunction construction and carbon-coating engineering for facilitating charge transfer and electron transport are considered viable strategies to address the challenges associated with the low rate capability and poor cycling stability of sulfide-based anodes in potassium-ion batteries (PIBs). Motivated by these concepts, we have successfully prepared a hydrangea-like bimetallic sulfide heterostructure encapsulated in nitrogen-doped carbon (FMS@NC) using a simple solvothermal method, followed by poly-dopamine wrapping and a one-step sulfidation/carbonization process. When served as an anode for PIBs, this FMS@NC demonstrates a high specific capacity (585 mAh g-1 at 0.05 A/g) and long cycling stability. Synergetic effects of mitigated volume expansions and enhanced conductivity that are responsbile for such high performance have been verified to originate from the heterostructured sulfides and the N-doped carbon matrix. Meanwhile, comprehensive characterization reveals existence of an intercalation-conversion hybrid K-ion storage mechanism in this material. Impressively, a K-ion capacitor with the FMS@NC anode and a commercial activated carbon cathode exhibits a superior energy density of up to 192 Wh kg-1, a high power density, and outstanding cycling stability. This study provides constructive guidance for designing high-performance and durable potassium-ion storage anodes for next-generation energy storage devices.

Effect of viral hepatitis on type 2 diabetes: A Mendelian randomization study.

BACKGROUND: The effects of viral hepatitis (VH) on type 2 diabetes (T2D) remain controversial. AIM: To analyze the causal correlation between different types of VH and T2D using Mendelian randomization (MR). METHODS: Single nucleotide polymorphisms of VH, chronic hepatitis B (CHB), chronic hepatitis C (CHC) and T2D were obtained from the BioBank Japan Project, European Bioinformatics Institute, and FinnGen. Inverse variance weighted, MR-Egger, and weighted median were used to test exposure-outcome associations. The MR-Egger intercept analysis and Cochran's Q test were used to assess horizontal pleiotropy and heterogeneity, respectively. Leave-one-out sensitivity analysis was used to evaluate the robustness of the MR analysis results. RESULTS: The MR analysis showed no significant causal relationship between VH and T2D in Europeans [odds ratio (OR) = 1.028; 95% confidence interval (CI): 0.995-1.062, P = 0.101]. There was a negative causal association between CHB and T2D among East Asians (OR = 0.949; 95%CI: 0.931-0.968, P < 0.001), while there was no significant causal association between CHC and T2D among East Asians (OR = 1.018; 95%CI: 0.959-1.081, P = 0.551). Intercept analysis and Cochran's Q test showed no horizontal pleiotropy or heterogeneity (P > 0.05). Sensitivity analysis showed that the results were robust. CONCLUSION: Among East Asians, CHB is associated with a reduced T2D risk, but this association is limited by HBV load and cirrhosis. Although VH among Europeans and CHC among East Asians are not associated with the risk of T2D, focusing on blood glucose in patients with CHC is still relevant for the early detection of T2D induced by CHC-mediated pathways of hepatic steatosis, liver fibrosis, and cirrhosis.

BMSCs-derived exosomes inhibit macrophage/microglia pyroptosis by increasing autophagy through the miR-21a-5p/PELI1 axis in spinal cord injury.

Spinal cord injury (SCI) results in a diverse range of disabilities and lacks effective treatment options. In recent years, exosomes derived from bone mesenchymal stem cells (BMSCs) have emerged as a promising cell-free therapeutic approach for treating ischemic brain injury and other inflammatory conditions. Macrophage/microglial pyroptosis has been identified as a contributing factor to neuroinflammation following SCI. The therapeutic potential of BMSC-derived exosomes in macrophage/microglia pyroptosis-induced neuroinflammation, however, has to be determined. Our findings demonstrate that exosomes derived from BMSCs can enhance motor function recovery and mitigate neuroinflammation subsequent to SCI by upregulating the expression of autophagy-related proteins and inhibiting the activation of NLRP3 inflammasomes in macrophage/microglia. Moreover, miR-21a-5p is markedly increased in BMSCs-derived exosomes, and knocking down miR-21a-5p in BMSCs-derived exosomes eliminates the beneficial effects of administration; upregulation of miR-21a-5p in BMSCs-derived exosomes enhances the beneficial effects of administration. Mechanistically, miR-21a-5p positively regulates the autophagy of macrophage/microglia by reducing PELI1 expression, which in turn inhibits their pyroptosis. This research provides novel evidence that exosomes derived from BMSCs can effectively suppress macrophage/microglia pyroptosis through the miR-21a-5p/PELI1 axis-mediated autophagy pathway, ultimately facilitating functional restoration following SCI. In particular, our constructed miR-21a-5p overexpression exosomes greatly improved the efficacy of BMSCs-derived exosomes in treating spinal cord injury. These results establish a foundation for the prospective utilization of exosomes derived from BMSCs as a novel biological intervention for spinal cord injury.

Association between electrocardiographic abnormalities and flood exposure among middle-aged and elderly people: A national longitudinal study in China.

BACKGROUND: Flooding has become more frequent and intensive due to climate change, particularly in Asian countries. However, evidence on the long-term health effects of floods from large-scale studies on the vulnerable aged population in China is insufficient. This study analyzed the long-term effects of exposure to flood on electrocardiographic (ECG) abnormalities, a commonly used indicator of cardiovascular disease (CVD) screening, in middle-aged and elderly people. METHOD: We evaluated the Chinese National Stroke Screening Survey data of 80,711 follow-up records from 38,375 participants aged > 40 years with two or more visits between 2013 and 2018 in this longitudinal study. Flood exposure was assessed as the presence of a satellite-detected flooded area within 500 m of the residence within 5 years before the survey date. The association between ECG abnormalities and flood exposure was analyzed using a random effects model with multiple adjustments. As age is an important CVD risk factor, a varying-coefficient function was derived to estimate the nonlinear modifying effect of age on the association between ECG abnormalities and flood exposure. The strata-specific associations between ECG abnormalities and flood exposure were applied to characterize vulnerability to flood. RESULTS: The fully adjusted model suggested that flood exposure was associated with an increased risk for ECG abnormalities among the middle-aged and elderly population (odds ratio [OR] 1.74, 95 % confidence interval [CI] 1.49, 2.03). The ORs of flood exposure for ECG suggesting atrial fibrillation, ST depression, and left ventricular hypertrophy were 1.85 (95 % CI 1.16, 2.94), 6.92 (95 % CI 5.23, 9.16), and 1.55 (95 % CI 0.66, 3.65), respectively. These associations were generally robust in various subpopulations, while a sublinear curve for the negative modifying effect of age was observed on the population vulnerability to flood. CONCLUSION: Flood exposure was associated with an increased long-term risk for an ECG abnormality. The need for effective measures to mitigate vulnerability to flood is not negligible in China.

Efficient Ion Percolating Network for High-Performance All-Solid-State Cathodes.

All-solid-state lithium batteries (ASSLBs) face critical challenges of low cathode loading and poor rate performances, which handicaps their energy/power densities. The widely-accepted aim of high ionic conductivity and low interfacial resistance seems insufficient to overcome these challenges. Here, it is revealed that an efficient ion percolating network in the cathode exerts a more critical influence on the electrochemical performance of ASSLBs. By constructing vertical alignment of Li0.35 La0.55 TiO3 nanowires (LLTO NWs) in solid-state cathode through magnetic manipulation, the ionic conductivity of the cathode increases twice compared with the cathode consisted of randomly distributed LLTO NWs. The all-solid-state LiFePO4 /Li cells using poly(ethylene oxide) as the electrolyte is able to deliver high capacities of 151 mAh g-1 (2 C) and 100 mAh g-1 (5 C) at 60 °C, and a room-temperature capacity of 108 mAh g-1 can be achieved at a charging rate of 2 C. Furthermore, the cell can reach a high areal capacity of 3 mAh cm-2 even with a practical LFP loading of 20 mg cm-2 . The universality of this strategy is also presented showing the demonstration in LiNi0.8 Co0.1 Mn0.1 O2 cathodes. This work offers new pathways for designing ASSLBs with improved energy/power densities.

Heterostructured CoS2/SnS2 encapsulated in sulfur-doped carbon exhibiting high potassium ion storage capacity.

Metallic sulfides are currently considered as ideal anode materials for potassium-ion batteries by virtue of their high specific capacities. However, their low intrinsic electronic conductivity, large volume variation and dissolution of polysulfides in electrochemical reactions hinder their further development toward practical applications. Here, we propose an effective structural design strategy by encapsulating CoS2/SnS2 in sulfur-doped carbon layers, in which internal voids are created to relieve the strain in the CoS2/SnS2 core, while the sulfur-doped carbon layer serves to improve the electron transport and inhibit the dissolution of polysulfides. These features enable the as-designed anode to deliver a high specific capacity (520 mAh/g at 0.1 A/g), a high rate capability (185 mA h g-1 at 10 A/g) and lifespan (0.016 % capacity loss per cycle up to 1500 cycles). Our comprehensive electrochemical characterization reveals that the heterostructure of CoS2/SnS2 not only promotes charge transfer at its interfaces, but also enhances the rate of K+ diffusion. Additionally, potassium-ion capacitors based on this novel anode are able to attain an energy density up to 162 Wh kg-1 and âˆ¼ 96 % capacity retention after 3000 cycles at 10 A/g.The demonstrated design rule combining morphological and structural engineering strategies sheds light on the development of advanced electrodes for high performance potassium-based energy storage devices.

Cryo-EM structure of HQNO-bound Alternative Complex III from the anoxygenic phototrophic bacterium Chloroflexus aurantiacus.

Alternative complex III (ACIII) couples quinol oxidation and electron acceptor reduction with potential transmembrane proton translocation. It is compositionally and structurally different from the cytochrome bc1/b6f complexes, but functionally replaces these enzymes in the photosynthetic and/or respiratory electron transport chains (ETCs) of many bacteria. However, the true compositions and architectures of ACIIIs remain unclear, as do their structural and functional relevance in mediating the ETCs. We here determined cryogenic electron microscopy structures of photosynthetic ACIII isolated from Chloroflexus aurantiacus (CaACIIIp), in apo-form and in complexed form bound to a menadiol analog 2-heptyl-4-hydroxyquinoline-N-oxide (HQNO). Besides six canonical subunits (ActABCDEF), the structures revealed conformations of two previously unresolved subunits, ActG and I, which contributed to the complex stability. We also elucidated the structural basis of menaquinol oxidation and subsequent electron transfer along the [3Fe-4S]-6 hemes wire to its periplasmic electron acceptors, using electron paramagnetic resonance (EPR), spectroelectrochemistry, enzymatic analyses and molecular dynamics (MD) simulations. A unique insertion loop in ActE was shown to function in determining the binding specificity of CaACIIIp for downstream electron acceptors. This study broadens our understanding of the structural diversity and molecular evolution of ACIIIs, enabling further investigation of the (mena)quinol oxidoreductases evolved coupling mechanism in bacterial energy conservation.

A spatial cell atlas of neuroblastoma reveals developmental, epigenetic and spatial axis of tumor heterogeneity.

Neuroblastoma is a pediatric cancer arising from the developing sympathoadrenal lineage with complex inter- and intra-tumoral heterogeneity. To chart this complexity, we generated a comprehensive cell atlas of 55 neuroblastoma patient tumors, collected from two pediatric cancer institutions, spanning a range of clinical, genetic, and histologic features. Our atlas combines single-cell/nucleus RNA-seq (sc/scRNA-seq), bulk RNA-seq, whole exome sequencing, DNA methylation profiling, spatial transcriptomics, and two spatial proteomic methods. Sc/snRNA-seq revealed three malignant cell states with features of sympathoadrenal lineage development. All of the neuroblastomas had malignant cells that resembled sympathoblasts and the more differentiated adrenergic cells. A subset of tumors had malignant cells in a mesenchymal cell state with molecular features of Schwann cell precursors. DNA methylation profiles defined four groupings of patients, which differ in the degree of malignant cell heterogeneity and clinical outcomes. Using spatial proteomics, we found that neuroblastomas are spatially compartmentalized, with malignant tumor cells sequestered away from immune cells. Finally, we identify spatially restricted signaling patterns in immune cells from spatial transcriptomics. To facilitate the visualization and analysis of our atlas as a resource for further research in neuroblastoma, single cell, and spatial-omics, all data are shared through the Human Tumor Atlas Network Data Commons at www.humantumoratlas.org.

Biogenic Selenium Nanoparticles Synthesized by L. brevis 23017 Enhance Aluminum Adjuvanticity and Make Up for its Disadvantage in Mice.

The most popular vaccine adjuvants are aluminum ones, which have significantly reduced the incidence and mortality of many diseases. However, aluminum-adjuvanted vaccines are constrained by their limited capacity to elicit cellular and mucosal immune responses, thus constraining their broader utilization. Biogenic selenium nanoparticles are a low-cost, environmentally friendly, low-toxicity, and highly bioactive form of selenium supplementation. Here, we purified selenium nanoparticles synthesized by Levilactobacillus brevis 23017 (L-SeNP) and characterized them using Fourier-transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, scanning electron microscopy, and transmission electron microscopy. The results indicate that the L-SeNP has a particle size ranging from 30 to 200 nm and is coated with proteins and polysaccharides. Subsequently, we assessed the immune-enhancing properties of L-SeNP in combination with an adjuvant-inactivated Clostridium perfringens type A vaccine using a mouse model. The findings demonstrate that L-SeNP can elevate the IgG and SIgA titers in immunized mice and modulate the Th1/Th2 immune response, thereby enhancing the protective effect of aluminum-adjuvanted vaccines. Furthermore, we observed that L-SeNP increases selenoprotein expression and regulates oxidative stress in immunized mice, which may be how L-SeNP regulates immunity. In conclusion, L-SeNP has the potential to augment the immune response of aluminum adjuvant vaccines and compensate for their limitations in eliciting Th1 and mucosal immune responses.

"Fishbone" Design of Amino/N-Spirocyclic Cations toward High-Performance Poly(triphenylene piperidine) Anion-Exchange Membranes for Fuel Cells.

N-Spirocyclic cations have excellent alkali resistance stability, and precise design of the structure of N-spirocyclic anion-exchange membranes (AEMs) improves their comprehensive performance. Here, we design and synthesize high-performance poly(triphenylene piperidine) membranes based on the "fishbone" design of amino/N-spirocyclic cations. The "fishbone" design does not disrupt the overall stabilized conformation but promotes a microphase separation structure, while exerting the synergistic effect of piperidine cations and spirocyclic cations, resulting in a membrane with good conductivity and alkali resistance stability. The hydroxide conductivity of the QPTPip-ASU-X membrane reached up to 133.5 mS cm-1 at 80 °C. The QPTPip-ASU-15 membrane was immersed in a 2 M NaOH solution at 80 °C for 1200 h, and the conductivity was maintained at 91.02%. In addition, the QPTPip-ASU-5 membrane had the highest peak power density of 255 mW cm-2.

Pulsatile microvascular cerebral blood flow waveforms change with intracranial compliance and age.

Significance: Diffuse correlation spectroscopy (DCS) is an optical method to measure relative changes in cerebral blood flow (rCBF) in the microvasculature. Each heartbeat generates a pulsatile signal with distinct morphological features that we hypothesized to be related to intracranial compliance (ICC). Aim: We aim to study how three features of the pulsatile rCBF waveforms: the augmentation index (AIx), the pulsatility index, and the area under the curve, change with respect to ICC. We describe ICC as a combination of vascular compliance and extravascular compliance. Approach: Since patients with Chiari malformations (CM) (n=30) have been shown to have altered extravascular compliance, we compare the morphology of rCBF waveforms in CM patients with age-matched healthy control (n=30). Results: AIx measured in the supine position was significantly less in patients with CM compared to healthy controls (p<0.05). Since physiologic aging also leads to changes in vessel stiffness and intravascular compliance, we evaluate how the rCBF waveform changes with respect to age and find that the AIx feature was strongly correlated with age (Rhealthy subjects=-0.63, Rpreoperative CM patient=-0.70, and Rpostoperative CM patients=-0.62, p<0.01). Conclusions: These results suggest that the AIx measured in the cerebral microvasculature using DCS may be correlated to changes in ICC.