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BACKGROUND & AIMS: The optimal timing of measurement and hemodynamic targets of portacaval pressure gradient (PPG) after TIPS remains inconclusive. This study aimed to identify the ideal moment of hemodynamic measurements and the optimal target of PPG in patients undergoing covered TIPS for variceal bleeding. METHODS: Between May 2018 and December 2021, 466 consecutive patients with recurrent variceal bleeding treated with covered TIPS were prospectively included. Post-TIPS PPG were measured immediately (immediate PPG), 24-72 hours (early PPG), and again 1 month (late PPG) after TIPS placement. The agreement among PPGs measured at different time points was assessed by intra-class correlation coefficient (ICC) and Bland-Altman method. The unadjusted and confounder-adjusted effects of PPGs on the clinical outcomes (portal hypertension complications [PHC], overt hepatic encephalopathy [OHE], further decompensation, and death) were assessed using Fine and Gray competing risk regression models. RESULTS: The agreement between early PPG and late PPG (ICC: 0.34) was better than that between immediate PPG and late PPG (ICC: 0.23, p<0.001). Early PPG revealed an excellent predictive value for PHC risk (early PPG ≥ vs <12 mmHg: adjusted HR [95%CI]: 2.17 [1.33-3.55], p=0.002) as well as OHE (0.40 [0.17-0.91], p=0.030) while immediate PPG did not. Late PPG showed a predictive value for PHC risk but not OHE. By targeting the lowest risk of further decompensation, we identified an optimal hemodynamic target with early PPG ranging 11 to 14 mmHg that was associated with a decreased risk of OHE while effectively preventing PHC. CONCLUSIONS: PPG measured 24 to 72 hours after TIPS correlates with long term PPG and clinical outcomes, and hemodynamic target with a PPG 11-14 mmHg reduced encephalopathy but not compromised clinical efficacy. IMPACT AND IMPLICATIONS: The optimal timing of measurement and hemodynamic targets of portacaval pressure gradient (PPG) after transjugular intrahepatic portosystemic shunt (TIPS) remains inconclusive. Here we show that post-TIPS PPG measured at least 24 hours but not immediately after the procedure correlated with long-term PPG and clinical events, therefore should be used for decision making in order to improve clinical outcomes. Targeting post-TIPS PPG at 11-14 mmHg or 20%-50% relative reduction from pre-TIPS baseline that measured 24-72 hours after procedure reduced encephalopathy but not compromised clinical efficacy, therefore could be used to guide TIPS creation and revision in patients with cirrhosis and variceal bleeding undergoing covered TIPS. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, ID: NCT03590288.
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Throughout the history of coal mining in all countries of the world, large areas of goaf have been left behind, and sudden collapses and surface subsidence of large areas of goaf may occur, especially for mining areas with long mining cycles. The northern new district of the Liaoyuan mining area has been subjected to nearly half a century of mining activities, accompanied by a gradual accumulation of disasters, which have occurred frequently in recent years. In order to assess the stability of the goaf in the study area, this paper proposes a hybrid decision-making multi-factor integrated evaluation method. The distribution of underground goafs was determined using geophysical exploration techniques (seismic survey and transient electromagnetic method) and geological drilling exploration. First, an evaluation index system was established based on the specifications of the goaf, the ecological and geological environment, and the mining conditions; the system included 14 indicators. Two weight calculation methods, AHP-EWM, were employed to determine the comprehensive weight of each indicator by combining subjective and objective weights on the basis of improved game theory. Subsequently, the fuzzy comprehensive evaluation method was utilised to complete the stability rating of each block in the study area, and MapGIS and ArcGIS were employed to complete the drawing of the stability zoning map of the northern new district goaf. The study area was divided into three zones of stability, basic stability and instability, according to the critical value. These zones accounted for 23.03%, 36.45% and 40.52% of the total area of the study area, respectively. The comprehensive on-site investigation revealed a decrease in the size and number of collapse pits and the rate of damage to the houses from the unstable zone to the stable zone. This indicates that the results of the division are consistent with the actual situation. The classification results are consistent with the actual ground disaster situation, thus verifying the rationality and validity of the evaluation method. The results indicate that the stability of the study area is generally at the lower middle level.
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Silicon (Si) is an appealing choice of anode for next-generation lithium ion batteries with high energy density, but its dramatic volume expansion makes it a tremendous challenge to achieve acceptable stability. Herein, we demonstrate that no capacity decay is observed during the testing period when the lithiation depth of Si nanoparticles is regulated at 2000 mAh g-1 or below, the fracture of Si anode films is well mitigated under suitable regulation of lithiation depth, and the cycled Si remains particulate without turning flocculent as under full lithiation. In addition, the solid electrolyte interphase (SEI) with a LiF-dominated outer region produced under lithiation regulation could better passivate the Si anodes and prevent further electrolyte decomposition than the mosaic-type SEI formed under full lithiation. Regulating lithiation depth proved to be a feasible solution to the pressing volume issues, and optimization of capacity utilization should be considered as much as materials-level optimization.
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Acetonitrile (AN) is a compelling electrolyte solvent for high-voltage and fast-charging batteries, but its reductive instability makes it incompatible with lithium metal anodes (LMAs). Herein, 1,1,2,2-tetrafluoroethyl-2,2,3,3-tetrafluoropropyl ether (TTE) is used as the diluent to build an AN-based local high-concentration electrolyte (LHCE) to realize dense, dendrite-free, and stable LMAs. Such LHCE exhibits an exceptional electrochemical stability window close to 6 V (vs Li+/Li), excellent wettability, and promising flame retardancy. Compared to a baseline carbonate-based electrolyte, its electrochemical performance is prominent: the overpotential of lithium nucleation is minimal (only 24 mV), the average half-cell coulombic efficiency (CE) reaches 99.5% at 0.5 mA cm-2, and its practicality in full cells with LiFePO4 (LFP) and LiNi0.8Co0.1Mn0.1O2 (NCM811) cathodes is also demonstrated. Compounding factors are identified to decipher the superiority of the AN-based LHCE. From the respect of solvation structures, both the elimination of free AN molecule and the diluent separation would contribute to prevention of anodic AN decomposition. Based on cryogenic electron microscopy (Cryo-EM) characterization and theoretical simulations results, the produced solid-electrolyte interphase (SEI) layer is uniform and compact. Thus, this work demonstrates a successful application of AN-based electrolytes in LMAs-traditionally deemed impractical-via the combined regulation of solvation and SEI structures.
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Utilizing a randomized control design, this mixed method study aimed to assess the impact of a personalized music intervention on mood, agitation level, and psychotropic drug use in individuals with moderate to advanced dementia residing in long-term care facilities. The sample comprised of 261 participants, with 148 in the intervention group and 113 in the control group. Data were collected from three sources: quantitative data from the Minimum Data Set and the Cohen-Mansfield Agitation Inventory, observational data of music-listening sessions, and an administrator survey regarding the lead staff person's perceptions of the intervention. Findings, based on Mixed Effect Models and content analyses, revealed positive impacts of the personalized music intervention on residents living with dementia. This low-cost, easily implementable intervention, requiring no special licensure for administration, can significantly enhance the quality of life for nursing facility residents.
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BACKGROUND: We hypothesized that alemtuzumab use is safe in pediatric kidney transplant recipients (KTRs) with equivalent long-term outcomes compared to other induction agents. METHODS: Using pediatric kidney transplant recipient data in the UNOS database between January 1, 2000, and June 30, 2022, multivariate logistic regression, multivariable Cox regression, and survival analyses were utilized to estimate the likelihoods of 1st-year and all-time hospitalizations, acute rejection, CMV infection, delayed graft function (DGF), graft loss, and patient mortality among recipients of three common induction regimens (ATG, alemtuzumab, and basiliximab). RESULTS: There were no differences in acute rejection or graft failure among induction or maintenance regimens. Basiliximab was associated with lower odds of DGF in deceased donor recipients (OR 0.77 [0.60-0.99], p = .04). Mortality was increased in patients treated with steroid-containing maintenance (HR 1.3 [1.005-1.7] p = .045). Alemtuzumab induction correlated with less risk of CMV infection than ATG (OR 0.76 [0.59-0.99], p = .039). Steroid-containing maintenance conferred lower rate of PTLD compared to steroid-free maintenance (HR 0.59 [0.4-0.8] p = .001). Alemtuzumab was associated with less risk of hospitalization within 1 year (OR 0.79 [0.67-0.95] p = .012) and 5 years (HR 0.54 [0.46-0.65] p < .001) of transplantation. Steroid maintenance also decreased 5 years hospitalization risk (HR 0.78 [0.69-0.89] p < .001). CONCLUSIONS: Pediatric KTRs may be safely treated with alemtuzumab induction without increased risk of acute rejection, DGF, graft loss, or patient mortality. The decreased risk of CMV infections and lower hospitalization rates compared to other agents make alemtuzumab an attractive choice for induction in pediatric KTRs, especially in those who cannot tolerate ATG.
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Alemtuzumab , Basiliximab , Rejeição de Enxerto , Hospitalização , Imunossupressores , Transplante de Rim , Humanos , Alemtuzumab/uso terapêutico , Criança , Masculino , Hospitalização/estatística & dados numéricos , Feminino , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Adolescente , Pré-Escolar , Basiliximab/uso terapêutico , Lactente , Sobrevivência de Enxerto , Soro Antilinfocitário/uso terapêutico , Resultado do Tratamento , Estudos Retrospectivos , Função Retardada do Enxerto/epidemiologia , Infecções por CitomegalovirusRESUMO
The development of low-temperature lithium metal batteries (LMBs) encounters significant challenges because of severe dendritic lithium growth during the charging/discharging processes. To date, the precise origin of lithium dendrite formation still remains elusive due to the intricate interplay between the highly reactive lithium metal anode and organic electrolytes. Herein, we unveil the critical role of interfacial defluorination kinetics of localized high-concentration electrolytes (LHCEs) in regulating lithium dendrite formation, thereby determining the performance of low-temperature LMBs. We investigate the impact of solvation structures of LHCEs on low-temperature LMBs by employing tetrahydrofuran (THF) and 2-methyltetrahydrofuran (2-MeTHF) as comparative solvents. The combination of comprehensive characterizations and theoretical simulations reveals that the THF-based LHCE featured with a strong solvation strength exhibits fast interfacial defluorination reaction kinetics, thus leading to the formation of an amorphous and inorganic-rich solid-electrolyte interphase (SEI) that can effectively suppress the growth of lithium dendrites. As a result, the highly reversible Li metal anode achieves an exceptional Coulombic efficiency (CE) of up to â¼99.63% at a low temperature of -30 °C, thereby enabling stable cycling of low-temperature LMB full cells. These findings underscore the crucial role of electrolyte interfacial reaction kinetics in shaping SEI formation and provide valuable insights into the fundamental understanding of electrolyte chemistry in LMBs.
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Introduction: Transplantation is a field with unique medical and administrative challenges that involve an equally diverse array of stakeholders. Expectantly, the litigation stemming from this field should be similarly nuanced. There is a paucity of comprehensive reviews characterizing this medicolegal landscape. Design: The Caselaw Access Project Database was used to collect official court briefs of 2053 lawsuits related to kidney, liver, heart, lung, and pancreas transplantation. A thematic analysis was undertaken to characterize grounds for litigation, defendant type, and outcomes. Cases were grouped into policy, discrimination, poor or unsuccessful outcome, or other categories. Results: One hundred sixty-four court cases were included for analysis. Cases involving disputes over policy coverage were the most common across all organ types (N = 55, 33.5%). This was followed by poor outcomes (N = 51, 31.1%), allegations of discrimination against prison systems and employers (N = 37, 22.6%) and other (N = 21, 12.8%). Defendants involved in discrimination trials won with the greatest frequency (N = 29, 90.62%). Defendants implicated in policy suits won 65.3% (N = 32), poor outcomes 62.2% (N = 28), and other 70% (N = 14). Of the 51 cases involving poor outcomes, plaintiffs indicated lack of informed consent in 23 (45.1%). Conclusion: Reconsidering the informed consent process may be a viable means of mitigating future legal action. Most discrimination suits favoring defendants suggested previous concerns of structural injustices in transplantation may not be founded. The prevalence of policy-related cases could be an indication of financial burden on patients. Future work and advocacy will need to substantiate these concerns and address change where legal recourse falls short.
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Imperícia , Transplante de Órgãos , Humanos , Transplante de Órgãos/legislação & jurisprudência , Imperícia/legislação & jurisprudência , Imperícia/estatística & dados numéricos , Estados Unidos , Preconceito , Política de Saúde/legislação & jurisprudênciaRESUMO
In this work, a novel boehmite-modified carbon adsorbent (BMCC) derived from moldy corn was used for simultaneous removal of P and bisphenol A (BPA) from livestock wastewater. The results showed that BMCC had a high specific surface area (308.82 m2/g) with boehmite nanoparticles anchored on its surface. BMCC showed high P and BPA decontamination capabilities (40.98 mg/g for P and 54.65 mg/g for BPA by Langmuir model). The adsorbed amount of P declined as pH increased from 4 to 10, while the adsorbed amount of BPA remained steady until pH increased to 10. After 6 cycles of BMCC use, the P and BPA adsorption efficiencies reduced by 21.75 % and 19.41 %, respectively. The adsorption of P was dominated by electrostatic attraction and complexation, while the adsorption of BPA was controlled by hydrogen bonding, electrostatic interaction, and π-π association. In conclusion, BMCC is an effective treatment for decontaminating P- and BPA-contaminated livestock wastewater.
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Hidróxido de Alumínio , Óxido de Alumínio , Carbono , Fenóis , Poluentes Químicos da Água , Animais , Águas Residuárias , Gado , Fósforo , Descontaminação , Cinética , Compostos Benzidrílicos , Adsorção , Concentração de Íons de HidrogênioRESUMO
Anion-exchange membrane fuel cells (AEMFCs) are promising alternative hydrogen conversion devices. However, the sluggish kinetics of the hydrogen oxidation reaction in alkaline media hinders further development of AEMFCs. As a synthesis method commonly used to prepare disordered PtRu alloys, the impregnation process is ingeniously designed herein to synthesize sub-3 nm Pt@Ru core-shell nanoparticles by sequentially reducing Pt and Ru at different annealing temperatures. This method avoids complex procedures and synthesis conditions for organic synthesis systems, and the atomic structure evolution of the synthesized core-shell nanoparticles can be tracked. The synthesized Pt@Ru electrocatalyst shows an ultrasmall average size of â¼2.5 nm and thereby a large electrochemical surface area (ECSA) of 166.66 m2 gPt+Ru-1. Exchange current densities (j0) normalized to the mass (Pt + Ru) and ECSA of this electrocatalyst are 8.0 and 5.8 times as high as those of commercial Pt/C, respectively. To the best of our knowledge, the achieved mass-normalized j0 measured by rotating disk electrodes is the highest reported so far. The membrane electrode assembly test of the Pt@Ru electrocatalyst shows a peak power density of 1.78 W cm-2 (0.152 mgPt+Ru cmanode-2), which is higher than that of commercial PtRu/C (1.62 W cm-2, 0.211 mgPt+Ru cmanode-2). The improvement of the intrinsic activity can be attributed to the electron transfer from the Ru shell to the Pt core, and the ultrafine particles further enhance the mass activity. This work reveals the feasibility of using simple impregnation to synthesize fine core-shell nanocatalysts and the importance of investigating the atomic structure of PtRu nanoparticles and other disordered alloys.
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This study aimed to estimate the prevalence of illegal kidney sales in Kalai Upazila, Bangladesh, using the Network Scale-Up Method (NSUM), an ego-centric network survey-based technique used to estimate the size of hidden populations. The study estimated the size of the kidney seller population, analysed the profiles of kidney sellers and kidney brokers and investigated the characteristics of villagers who are more likely to be connected to kidney sellers to identify possible biases of the NSUM estimate. The study found that the prevalence of kidney trafficking in Kalai Upazila was between 1.98% and 2.84%, which is consistent with the estimates provided by a local leader and reporters, but with much narrower bounds. The study also found that a large proportion of kidney sellers and brokers were men (over 70% and 90%, respectively) and relatively young (mean age of 33 and 39, respectively). Specific reasons for kidney sales included poverty (83%), loan payment (4%), drug addiction (2%) and gambling (2%). While most reported male sellers were farmers (56%) and female sellers were housewives (78%) in need of money, most reported brokers were characterised as rich, well-known individuals.
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Rim , Pobreza , Adulto , Feminino , Humanos , Masculino , Bangladesh , Prevalência , Inquéritos e Questionários , Obtenção de Tecidos e ÓrgãosRESUMO
Emerging dual-graphite batteries (DGBs) capture extensive interest for their high output voltage and exceptional cost-effectiveness. Yet, developing electrolytes compatible with both the cathode and anode stands to be a tremendous challenge, and how electrolyte impacts anion and cation intercalation into graphite remains inexplicit or controversial. Herein, we have evaluated the performance of graphite anode and cathode in typical ethyl methyl carbonate (EMC) based electrolytes and unveiled their electrode-electrolyte interphase using Cryogenic transmission electron microscopy (Cryo-TEM). The addition of fluoroethylene carbonate (FEC) brings substantial improvement in cycle stability and Coulombic efficiency for both the graphite cathode and anode, but its implication on cation and anion intercalation differs. FEC is involved in anodic side reactions to produce a LiF-embedded solid-electrolyte interphase layer. It is much thinner and more uniform than that formed in the electrolyte without FEC, which is correlated with less graphite exfoliation and enhanced stability. As for the graphite cathode, both basal and edge planes are largely bare, and only few scattered byproducts are found. In addition, we also reveal layer bending and local lattice disordering of the graphite cathode based on multiple Cryo-TEM images, which are speculated to be caused by high lattice strain induced by anion intercalation and local oxidation under high voltage. The absence of cathode-electrolyte interphase (CEI) layers overturns the paradigm of attributing cathodic performance to CEI features and is regarded as a fundamental reason for severe self-discharge of graphite cathode. FEC helps to alleviate graphite exfoliation issues and enhance cycle stability, and we ascribe it to weakened solvation, which means reduced probability of solvent co-intercalation during charging, rather than compositional changes of cathodic byproducts.
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Most attempts to synthesize supramolecular nanosystems are limited to a single mechanism, often resulting in the formation of nanomaterials that lack diversity in properties. Herein, hierarchical assemblies with appropriate variety are fabricated in bulk via a superstructure-induced organic-inorganic hybrid strategy. The dynamic balance between substructures and superstructures is managed using covalent organic frameworks (COFs) and metal-organic frameworks (MOFs) as dual building blocks to regulate the performances of hierarchical assemblies. Significantly, the superstructures resulting from the controlled cascade between COFs and MOFs create highly active photocatalytic systems through multiple topologies. Our designed tandem photocatalysis can precisely and efficiently regulate the conversion rates of bioactive molecules (benzo[d]imidazoles) through competing redox pathways. Furthermore, benzo[d]imidazoles catalyzed by such supramolecular nanosystems can be isolated in yields ranging from 70 % to 93 % within tens of minutes. The multilayered structural states within the supramolecular systems demonstrate the importance of hierarchical assemblies in facilitating photocatalytic propagation and expanding the structural repertoire of supramolecular hybrids.
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Lithium (Li) metal is considered as the "holy grail" of anode materials for next-generation high energy batteries. However, notorious dendrite growth and interfacial instability could induce irreversible capacity loss and safety issues, limiting the practical application of Li metal anodes. Herein, we develop a novel approach to construct a borate-based artificial solid-electrolyte interphase (designated as B-SEI) through the reaction of metallic Li with triethylamine borane (TEAB). According to our cryogenic electron microscopy (Cryo-EM) characterization results, the artificial SEI adopts a glass-crystal bilayer structure, which facilitates uniform Li-ion transport and inhibits dendrite growth during Li plating. Benefiting from such an artificial SEI, the Li anode delivers an improved rate performance and prolonged cycle life. The symmetric Li/B-SEI||Li/B-SEI cell can maintain stable cycling for 700 h at a high current density of 3 mA cm-2. The full-cell pairing Li/B-SEI with LiFePO4 only exhibits minimal capacity decay after 500 cycles in a conventional carbonate-based electrolyte. This work demonstrates the feasibility of building a boride-based artificial SEI to stabilize the Li metal anode based on microscopic characterization results and comprehensive electrochemical data, which represents a promising avenue to develop practical Li metal batteries.
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Synthetic macrocycles have proved to be of great application value in functional charge-transfer systems in the solid state in recent years. Here we show a switchable on-off type vapochromic system toward 1-/2-bromoalkane isomers by constructing solid-state charge-transfer complexes between electron-rich perethylated pillar[5]arene and electron-deficient aromatic acceptors including 4-nitrobenzonitrile and 1,4-dinitrobenzene. These charge-transfer complexes with different colors show opposite color changes upon exposure to the vapors of 1-bromoalkanes (fading) and 2-bromoalkanes (deepening). Single-crystal structures incorporating X-ray powder diffraction and spectral analyses demonstrate that this on-off type vapochromic behavior is mainly attributed to the destruction (off) and reconstruction (on) of the charge-transfer interactions between perethylated pillar[5]arene and the acceptors, for which the competitive host-guest binding of 1-bromoalkanes and the solid-state structural transformation triggered by 2-bromoalkanes are respectively responsible. This work provides a simple colorimetric method for distinguishing positional isomers with similar physical and chemical properties.
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This study analyzed data from the National COVID Cohort Collaborative (N3C) database to investigate whether high-density lipoprotein (HDL) and its major protein component, apolipoprotein A1 (apoA1), are associated with severe COVID-19 sequelae, specifically acute kidney injury (AKI) and severe COVID-19 disease as defined by the infection resulting in hospitalization, extracorporeal membrane oxygenation (ECMO), invasive ventilation, or death. Our study included a total of 1,415,302 subjects with HDL values and 3589 subjects with apoA1 values. Higher levels of both HDL and apoA1 were associated with a lower incidence of infection as well as a lower incidence of severe disease. Higher HDL levels were also associated with a lower incidence of developing AKI. Most comorbidities were negatively correlated with SARS-CoV-2 infection, presumably due to the behavioral changes that occurred as a result of the precautions taken by individuals with underlying comorbidities. The presence of comorbidities, however, was associated with developing severe COVID-19 disease and AKI. African American and Hispanic populations experienced worse outcomes, including a higher incidence of infection and the development of severe disease, as well as AKI. Smoking and being male were associated with a lower incidence of infection, while they were risk factors for the development of severe disease and AKI. The results on cholesterol and diabetes drugs warrant further research, given that the database included multiple drugs in each category impeding for analysis of specific medications. Despite the current limitations in the N3C data, this study is the first to investigate the roles of HDL and apoA1 on the outcomes of COVID-19 using the US population data.
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The electrolyte solvation structure and the solid-electrolyte interphase (SEI) formation are critical to dictate the morphology of lithium deposition in organic electrolytes. However, the link between the electrolyte solvation structure and SEI composition and its implications on lithium morphology evolution are poorly understood. Herein, we use a single-salt and single-solvent model electrolyte system to systematically study the correlation between the electrolyte solvation structure, SEI formation process and lithium deposition morphology. The mechanism of lithium deposition is thoroughly investigated using cryo-electron microscopy characterizations and computational simulations. It is observed that, in the high concentration electrolytes, concentrated Li+ and anion-dominated solvation structure initiate the uniform Li nucleation kinetically and favor the decomposition of anions rather than solvents, resulting in inorganic-rich amorphous SEI with high interface energy, which thermodynamically facilitates the formation of granular Li. On the contrary, solvent-dominated solvation structure in the low concentration electrolytes tends to exacerbate the solvolysis process, forming organic-rich mosaic SEI with low interface energy, which leads to aggregated whisker-like nucleation and growth. These results are helpful to tackle the long-standing question on the origin of lithium dendrite formation and guide the rational design of high-performance electrolytes for advanced lithium metal batteries.
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Terbuthylazine (TBA) is an emerging environmental contaminant that poses moderate to high risk to non-target organisms. In this study, a newly TBA-degrading strain, Agrobacterium rhizogenes AT13, was isolated. This bacterium degraded 98.7% of TBA (100 mg/L) within 39 h. Based on the six detected metabolites, three novel pathways of strain AT13, including dealkylation, deamination-hydroxylation, and ring-opening reactions, were proposed. The risk assessment demonstrated that most degradation products might be substantially less harmful than TBA. Whole-genome sequencing and RT-qPCR analysis revealed that ttzA, which encodes S-adenosylhomocysteine deaminase (TtzA), is closely related to TBA degradation in AT13. Recombinant TtzA showed 75.3% degradation of 50 mg/L of TBA within 13 h and presented a Km value of 0.299 mmol/L and a Vmax value of 0.041 mmol/L/min. The molecular docking results indicated that the binding energy of TtzA to TBA was -32.9 kcal/mol and TtzA residue ASP161 formed two hydrogen bonds with TBA at distances of 2.23 and 1.80 Å. Moreover, AT13 efficiently degraded TBA in water and soil. Overall, this study provides a foundation for the characterization and mechanism of TBA biodegradation and may enhance our understanding of the TBA biodegradation by microbes.
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Agrobacterium , Bactérias , Simulação de Acoplamento Molecular , Agrobacterium/genética , Biodegradação AmbientalRESUMO
OBJECTIVE: Necroptosis, as a form of regulated cell necrosis, could participate in myocardial oxidative damage. We investigated whether donepezil attenuates H2O2-induced oxidative stress injury and necroptosis in rat cardiomyocytes. METHODS: H9c2 cells were incubated with H2O2 (final concentration of 1 mM) and then intervened with donepezil at doses of 2.5 and 10 µM. Subsequently, the necroptosis inhibitor necrostatin-1 (Nec-1) was introduced to treat H9c2 cells. For cell function experiments, cell proliferation; the contents of creatine kinase (CK), lactate dehydrogenase (LDH), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and malondialdehyde (MDA); the protein and mRNA levels of the necroptosis-related proteins receptor-interacting serine-threonine kinase 3 (RIP3) and mixed lineage kinase-like (MLKL); and calcium ion fluorescence intensity were detected using Cell Counting Kit-8, enzyme-linked immunosorbent assay (ELISA), Western blotting, quantitative reverse transcription polymerase chain reaction, and flow cytometry, respectively. RESULTS: Cell viability was conspicuously decreased; CK and LDH contents, RIP3 and MLKL expression levels, and MDA production were preeminently elevated; and the production of SOD, CAT, and GSH was prominently reduced under H2O2 stimulation, which were dose-dependently countered by donepezil intervention. Nec-1 decreased the cell necroptosis, oxidative stress, and calcium overload caused by H2O2. However, on the premise of donepezil intervention, the addition of Nec-1 failed to further improve the situation, suggesting that donepezil exerts cardioprotective effects partly by inhibiting RIP3 and MLKL levels. CONCLUSION: Donepezil reduced H2O2-inflicted oxidative stress and necroptosis in cardiomyocytes by suppressing RIP3 and MLKL levels and calcium ion overload.
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Peróxido de Hidrogênio , Miócitos Cardíacos , Ratos , Animais , Peróxido de Hidrogênio/farmacologia , Donepezila/metabolismo , Donepezila/farmacologia , Necroptose , Cálcio/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/farmacologia , Estresse Oxidativo , Apoptose , Necrose/metabolismoRESUMO
BACKGROUND: Liver transplantation has inherent disparities but data is scarce in liver transplant (LT) candidates with acute alcohol-associated hepatitis (AAH). We aimed to investigate demographic inequities and its impact on survival outcomes among AAH LT candidates. METHODS: A retrospective analysis using the United Network of Organ Sharing database was conducted between 2000 and 2021. 25 981 LT recipients with alcohol-associated liver cirrhosis and 662 recipients with AAH were included. Waitlisted candidates were also evaluated. RESULTS: In comparison with alcohol-associated liver cirrhosis, AAH LT recipients were more likely Asian or "other" race and younger. Hispanics demonstrated better graft and patient survival (p < 0.05) but were less likely to be waitlisted and transplanted for AAH than for liver cirrhosis. Women with AAH were more likely to be waitlisted and transplanted. Pre-existing diabetes and male sex were associated with higher graft failure (25% and 8% respectively). Increasing recipient age were 2% more likely to experience negative outcomes. Chronicity of liver disease did not impact graft (p = 0.137) or patient survival (p = 0.145). CONCLUSION: Our results revealed demographic factors have a significant impact on transplant listing, organ allocation and survival outcomes. Further investigations are imperative to minimize disparities in LT evaluation and provide equity in healthcare.