Chronic increasing nitrogen and endogenous phosphorus release from sediment threaten to the water quality in a semi-humid region reservoir.

The water quality in the drinking water reservoir directly affects people's quality of life and health. When external pollution input is effectively controlled, endogenous release is considered the main cause of water quality deterioration. As the major nitrogen (N) and phosphorus (P) sources in reservoirs, sediment plays a vital role in affecting the water quality. To understand the spatial and temporal variation of N and P in the sediment, this study analyzed the current characteristics and cumulative effects of a semi-humid reservoir, Yuqiao Reservoir, in North China. The N and P concentrations in the reservoir sediment were decreased along the flow direction, while the minimum values were recorded at the central sediment profile. External input and algal deposition were the main factors leading to higher sediment concentrations in the east (Re-E) and west (Re-W) areas of reservoir sediment profiles. According to the long-term datasets, the peaks of both sediment total nitrogen content and deposition rate were observed in the 2010s, which has increased about three times and six times than in the1990s, respectively. Therefore, the increase in phosphorus concentration may be the main reason for eutrophication in water in recent years. The mineralization of organic matter has a significant promoting effect on releasing N and P from sediments, which will intensify eutrophication in water dominated by P and bring huge challenges to water environment management. This study highlights that the current imbalance in N and P inputs into reservoirs and the endogenous P release from sediment will have a significant impact on water quality.

Melatonin promotes cell cycle progression of neural stem cells subjected to manganese via Nurr1.

Excessive exposure to manganese (Mn) through drinking water and food during pregnancy significantly heightens the likelihood of neurodevelopmental damage in offspring. Multiple studies have indicated that melatonin (Mel) may help to relieve neurodevelopmental disorders caused by Mn, but potential mechanisms underlying this effect require further exploration. Here, we utilized primary neural stem cells (NSCs) as a model to elucidate the molecular mechanism underlying the protective function of Mel on Mn-induced cell proliferation dysfunction and cycle arrest. Our results showed that Mn disrupted the cell cycle in NSCs by suppressing positive regulatory proteins (CDK2, Cyclin A, Cyclin D1, and E2F1) and enhancing negative ones (p27KIP1 and p57KIP2), leading to cell proliferation dysfunction. Mel inhibited the Mn-dependent changes to these proteins and the cell cycle through nuclear receptor-related protein 1 (Nurr1), thus alleviating the proliferation dysfunction. Knockdown of Nurr1 using lentivirus-expressed shRNA in NSCs resulted in a diminished protective effect of Mel. We concluded that Mel mitigated Mn-induced proliferation dysfunction and cycle arrest in NSCs through Nurr1.

Conductive and capacitive network for enriching the exoelectrogens and enhancing the extracellular electron transfer in microbial fuel cells.

Although lots of nanomaterials modified anodes have been reported to improve the bacterial attachment and extracellular electron transfer (EET) in microbial fuel cells (MFCs), the lack of a three dimensional (3D) conductive and capacitive network severely limited MFCs performance. In this work, 3D conductive networks derived from mucor mycelia were grown on carbon cloth (CC), and capacitive FeMn phosphides/oxides were further anchored on these 3D networks by electrochemical deposition (denoted as FeMn/CMM@CC) to simultaneously address the above challenges. As a result, the multivalent metal active sites were evenly distributed on 3D conductive network, which favored the enrichment of exoelectrogens, mass transport and EET. Consequently, the as-prepared FeMn/CMM@CC anode displayed accumulated charge of 131.4C/m2, higher than bare CC. Meanwhile, FeMn/CMM@CC anode substantially promoted flavin excretion and the amounts of nano conduits. The abundance of Geobacter was 63 % on bare CC, and greatly increased to 83 % on FeMn/CMM@CC. MFCs equipped by FeMn/CMM@CC anode presented the power density of 3.06 W/m2 and coulombic efficiency (29.9 %), evidently higher than bare CC (1.29 W/m2, 7.3 %), and the daily chemical oxygen demand (COD) removal amount also increased to 92.6 mg/L/d. This work developed a facile method to optimize the abiotic-biotic interface by introducing 3D conductive and capacitive network, which was proved to be a promising strategy to modify macro-porous electrodes.

Prevalence of aggressive care among patients with cancer near the end of life: a systematic review and meta-analysis.

Background: Aggressive care near patients' end-of-life (EOL) entails limited therapeutic values, high costs, and compromised quality of life (QoL). In this study, we aimed to estimate the global prevalence of aggressive care in patients with cancer and explore potential subgroup differences. Methods: We searched PubMed, Embase, and the Cochrane Library from database inception to Feb 16, 2024. Eligible studies reported the prevalence of aggressive EOL care using at least one quantifiable measure. Random-effects models were used to derive the pooled prevalence and subgroup analyses were performed to investigate differences in the prevalence of aggressive care across regions, the country's level of economic development, tumor types, ages, and sample sizes. This review is registered with PROSPERO, number CRD42023467839. Findings: A total of 129 studies were included in this systematic review, of which 118 (91.5%) were from high-income countries. Studies were mostly conducted in the Americas (60, 46.5%), Europe (34, 26.4%), and Western Pacific (31, 24.0%). Measures of aggressive care were inconsistent across studies, with the most commonly used measure being the use of chemotherapy in the last 14 days of life (DOLs) (n = 87, 67.4%) and intensive care unit (ICU) stay in the last 30 DOLs (n = 87, 67.4%). The prevalence of the five claims-based measures of aggressive care, i.e., chemotherapy in the last 14 DOLs, ICU stay in the last 30 DOLs, repeated hospital admission in the last 30 DOLs, repeated emergency room (ER) visit in the last 30 DOLs, and hospice care <3 days before death were 11.6% (95% CI, 9.8%-13.4%), 14.4% (95% CI, 11.8%-17.0%), 17.9% (95% CI, 14.4%-21.4%), 14.8% (95% CI, 12.0%-17.6%), and 14.4% (95% CI, 11.2%-17.6%), respectively. Regional differences were statistically significant in the prevalence of ICU stay and repeated hospital admission in the last 30 DOLs (p < 0.01; p = 0.03). Patients with hematologic malignancies were more likely to receive aggressive care than those with solid tumors, as seen in their higher rates of chemotherapy in the last 14 DOLs (21.7% versus 11.6%; p = 0.03), ICU stay in the last 30 DOLs (25.5% versus 10.8%; p < 0.01), and hospice care <3 days before death (26.7% versus 14.2%; p < 0.01). In addition, the prevalence of chemotherapy in the last 14 DOLs (26.2%; p < 0.01) and repeated hospital admission in the last 30 DOLs (31.4%; p < 0.01) were highest among pediatric patients with cancer. Interpretation: This meta-analysis found that aggressive EOL care was common in patients with cancer, regardless of the definition used, and varied by regions and populations. It is necessary to be aware of the global burden of aggressive care for patients with cancer near their EOL and take prompt action to address it. Funding: National Natural Science Foundation of China (Grant No. 72274004).

Ni─Co─O─S Derived Catalysts on Hierarchical N-doped Carbon Supports with Strong Interfacial Interactions for Improved Hybrid Water Splitting Performance.

Simultaneously improving electrochemical activity and stability is a long-term goal for water splitting. Herein, hierarchical N-doped carbon nanotubes on carbon nanowires derived from PPy are grown on carbon cloth, serving as a support for NiCo oxides/sulfides. The hierarchical electrodes annealed in N2 or H2/N2 display improved intrinsic activity and stability for hydrogen evolution reaction (HER) and glucose oxidation reaction. Compared with Pt/C||Ir/C in alkaline media, the glucose electrolysis assembled with electrodes exhibits a cell voltage of 1.38 V at 10 mA cm-2, durability for >12 h at 50 mA cm-2, and resistance to glucose/gluconic acid poisoning. In addition, electrocatalysts can also be applied in ethanol oxidation reactions. Systematic characterizations reveal the strong interactions between NiCo and N-doped carbon support-induced partial charge transfer at the interface and regulate the local electronic structure of active sites. Density functional theory calculations demonstrate that the synergistic effect between N-doped carbon supports, metallic NiCo, and NiCo oxides/sulfides optimize the adsorption energy of H2O and the H* free energy for HER. The energy barrier of the dehydrogenation of glucose effectively decreased. This work will attract attention to the role of metal-support interactions in enhancing the intrinsic activity and stability of electrocatalysts.

Anticancer drug-induced interstitial lung disease: a critical appraisal of clinical practice guidelines and consensus statements.

Anticancer drug-induced interstitial lung disease (DIILD) has received increasing clinical attention, and the quality of relevant guidance documents has become critical. Our purpose was to assess the quality of documents for anticancer DIILD and summarize the recommendations. Clinical practice guidelines (CPGs) and consensus statements with recommendations were searched in electronic databases, websites of guideline organizations, and professional societies. The quality of documents was assessed using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) methodology, and the specific recommendations were aggregated and compared. A total of 11 documents were eligible, including 6 CPGs and 5 consensus statements, and the quality of AGREE II assessments differed greatly. The domains of scope and purpose and clarity of presentation received the highest median scores, while the stakeholder involvement domain received the lowest score. Recommendations were inconsistent between documents, particularly regarding the selection of steroid regimens. The methodological quality of the guidance documents needs to be enhanced, especially in the domain of stakeholder involvement. Inconsistencies exist in documents, and further discussions among multidisciplinary experts are needed. Particularly, differences in steroid regimens require attentions, and researches on the risks of adverse events and discovery of precise biomarkers are necessary.

Ethical and legal challenges of medical AI on informed consent: China as an example.

The escalating integration of Artificial Intelligence (AI) in clinical settings carries profound implications for the doctrine of informed consent, presenting challenges that necessitate immediate attention. China, in its advancement in the deployment of medical AI, is proactively engaging in the formulation of legal and ethical regulations. This paper takes China as an example to undertake a theoretical examination rooted in the principles of medical ethics and legal norms, analyzing informed consent and medical AI through relevant literature data. The study reveals that medical AI poses fundamental challenges to the accuracy, adequacy, and objectivity of information disclosed by doctors, alongside impacting patient competency and willingness to give consent. To enhance adherence to informed consent rules in the context of medical AI, this paper advocates for a shift towards a patient-centric information disclosure standard, the restructuring of medical liability rules, the augmentation of professional training, and the advancement of public understanding through educational initiatives.

An early warning model to predict acute kidney injury in sepsis patients with prior hypertension.

Background: In the context of sepsis patients, hypertension has a significant impact on the likelihood of developing sepsis-associated acute kidney injury (S-AKI), leading to a considerable burden. Moreover, sepsis is responsible for over 50 % of cases of acute kidney injuries (AKI) and is linked to an increased likelihood of death during hospitalization. The objective of this research is to develop a dependable and strong nomogram framework, utilizing the variables accessible within the first 24 h of admission, for the anticipation of S-AKI in sepsis patients who have hypertension. Methods: In this study that looked back, a total of 462 patients with sepsis and high blood pressure were identified from Nanfang Hospital. These patients were then split into a training set (consisting of 347 patients) and a validation set (consisting of 115 patients). A multivariate logistic regression analysis and a univariate logistic regression analysis were performed to identify the factors that independently predict S-AKI. Based on these independent predictors, the model was constructed. To evaluate the efficacy of the designed nomogram, several analyses were conducted, including calibration curves, receiver operating characteristics curves, and decision curve analysis. Results: The findings of this research indicated that diabetes, prothrombin time activity (PTA), thrombin time (TT), cystatin C, creatinine (Cr), and procalcitonin (PCT) were autonomous prognosticators for S-AKI in sepsis individuals with hypertension. The nomogram model, built using these predictors, demonstrated satisfactory discrimination in both the training (AUC = 0.823) and validation (AUC = 0.929) groups. The S-AKI nomogram demonstrated superior predictive ability in assessing S-AKI within the hypertension grade I (AUC = 0.901) set, surpassing the hypertension grade II (AUC = 0.816) and III (AUC = 0.810) sets. The nomogram exhibited satisfactory calibration and clinical utility based on the calibration curve and decision curve analysis. Conclusion: In patients with sepsis and high blood pressure, the nomogram that was created offers a dependable and strong evaluation for predicting S-AKI. This evaluation provides valuable insights to enhance individualized treatment, ultimately resulting in improved clinical outcomes.

Manganese disrupts the maturation and degradation of axonal autophagosome leading to hippocampal synaptic toxicity in mice via the activation of LRRK2 on phosphorylation of Rab10.

Manganese (Mn) overexposure induces hippocampal synaptotoxicity by the accumulation of dysfunctional synaptic vesicles (SVs). Leucine-rich repeat kinase 2 (LRRK2) kinase activity is involved in regulating axonal transport (autophagosomal maturation) and lysosomal function. Nevertheless, it remains unclear whether Mn-induced synaptotoxicity is associated with the LRRK2-mediated disruption of autophagosomal maturation in axonal transport and the impairment of lysosomes in hippocampal neurons. Here, we established models of manganism in C57BL/6 mice and hippocampal neuronal HT22 cells to verify the role of LRRK2-mediated Rab10 phosphorylation in the Mn-induced dysfunction of autophagy- lysosomal fusion. Our results proved that Mn-induced the disorder of axonal transport and that lysosome impairments were associated with the increased recruitment of phospho-Rab10 at the axon and lysosomes. Next, we established Lrrk2-KD and LRRK2 kinase- specific inhibitor (GNE-0877, GNE) pre-treated HT22 cells to inhibit Lrrk2 gene expression and kinase activity, respectively. In Mn-treated Lrrk2-KD or GNE-pretreated normal neurons, our results indicated that lysosomal pH and integrity and autophagic flow were restored, indicating by decreased levels of phospho-Rab10 on lysosomes and JNK-interacting proteins (JIP4). In addition, GNE pretreatment could provide protection against Mn-induced synaptotoxicity in vivo, which was evidenced by the partial recovery in synaptic plasticity and synaptic damage. Thus, the Mn-induced abnormal activation of LRRK2 affected lysosomes and the recruitment of phospho-Rab10 by JIP4, which disrupted autophagosomal maturation in proximal axons and resulted in the hippocampal synaptic toxicity of mice.

Melatonin modulates the differentiation of neural stem cells exposed to manganese via SIRT1/ß-catenin signaling.

Excessive exposure of children to manganese (Mn) in the environment has a bearing on developmental neurotoxicity. Although melatonin (Mel) can play a neuroprotective role by modulating the differentiation of neural stem cells (NSCs) in the developing brain, its specific mechanism under Mn overexposure remains to be explored. Here, we cultured primary NSCs as an available model to investigate the relevant molecular mechanism of Mel mitigation on Mn-induced disorder of NSCs differentiation through sirtuin 1 (SIRT1)/ß-catenin pathway. It was found that Mel could facilitate the differentiation of Mn-treated NSCs into neurons. Further, our results uncovered that the pro-differentiation mechanism of Mel depended upon ascending the activity of SIRT1, thereby weakening ß-catenin acetylation and increasing phosphorylation of ß-catenin ser675 in the cytoplasm, which facilitates the nuclear translocation of ß-catenin. Furthermore, the role of SIRT1 in Mel-mediated signal transduction was investigated through the pretreatment of NSCs using a highly specific SIRT1 inhibitor, EX527. After EX527 pretreatment, Mel could not maintain its protective effect. Overall, our results revealed that Mel could alleviate Mn-induced disorder of NSCs differentiation through the activation of the SIRT1/ß-catenin pathway.

A Synergistic Antibacterial Study of Copper-Doped Polydopamine on Ti3C2Tx Nanosheets with Enhanced Photothermal and Fenton-like Activities.

In response to the trend of drug-resistant and super bacteria, the existing single antibacterial methods are not sufficient to kill bacteria, and the development of multifunctional antibacterial nanomaterials is urgent. Our study aims to construct copper-doped polydopamine-coated Ti3C2Tx (CuPDA@Ti3C2Tx) with an enhanced photothermal property and Fenton-like activity. The nanocomposite hydrogel consisting of CuPDA@Ti3C2Tx and alginate can improve the antioxidant activity of two-dimensional MXene nanosheets by coating them with a thin layer of PDA nanofilm. Meanwhile, Cu ions are adsorbed through the coordination of PDA-rich oxygen-containing functional groups and amino groups. Calcium ions were further used to crosslink sodium alginate to obtain antibacterial hydrogel materials with combined chemotherapy and photothermal therapy properties. The photothermal conversion efficiency of CuPDA@Ti3C2Tx is as high as 57.7% and the antibacterial rate of Escherichia coli reaches 96.12%. The photothermal effect leads to oxidative stress in bacteria, increases cell membrane permeability, and a high amount of ROS and copper ions enter the interior of the bacteria, causing protein denaturation and DNA damage, synergistically leading to bacterial death. Our study involves a multifunctional synergistic antibacterial nanodrug platform, which is conducive to the development of high-performance antibacterial agents and provides important research ideas for solving the problem of drug-resistant bacteria.

Femtosecond Laser Direct Writing of Gecko-Inspired Switchable Adhesion Interfaces on a Flexible Substrate.

Biomimetic switchable adhesion interfaces (BSAIs) with dynamic adhesion states have demonstrated significant advantages in micro-manipulation and bio-detection. Among them, gecko-inspired adhesives have garnered considerable attention due to their exceptional adaptability to extreme environments. However, their high adhesion strength poses challenges in achieving flexible control. Herein, we propose an elegant and efficient approach by fabricating three-dimensional mushroom-shaped polydimethylsiloxane (PDMS) micropillars on a flexible PDMS substrate to mimic the bending and stretching of gecko footpads. The fabrication process that employs two-photon polymerization ensures high spatial resolution, resulting in micropillars with exquisite structures and ultra-smooth surfaces, even for tip/stem ratios exceeding 2 (a critical factor for maintaining adhesion strength). Furthermore, these adhesive structures display outstanding resilience, enduring 175% deformation and severe bending without collapse, ascribing to the excellent compatibility of the micropillar's composition and physical properties with the substrate. Our BSAIs can achieve highly controllable adhesion force and rapid manipulation of liquid droplets through mechanical bending and stretching of the PDMS substrate. By adjusting the spacing between the micropillars, precise control of adhesion strength is achieved. These intriguing properties make them promising candidates for various applications in the fields of microfluidics, micro-assembly, flexible electronics, and beyond.

Fermentation of Persimmon Leaves Extract by Lactiplantibacillus plantarum and Saccharomyces cerevisiae.

Persimmon leaves usually as agricultural and forestry waste were fermented by Lactiplantibacillus plantarum and Saccharomyces cerevisiae. Growth and metabolic performances of L. plantarum and S. cerevisiae, as well as the effect of fermentation on the antioxidant abilities of the extract was investigated, including the content of flavonoids, 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radical clearance rates. Growth of L. plantarum was limited, even though the acid production was sustainable, while S. cerevisiae was more suitable to inhabit in the persimmon leaves extract. A symbiotic relationship was observed between the two microbes, reflected in aspects of growth of S. cerevisiae, pH reduction, and ethanol production. The DPPH radical clearance rates of all groups decreased at the early period, and increased later. The co-culture group reached the second highest value of DPPH radical clearance rate only next to the single group of L. plantarum at 9 h. All groups showed an overall downward trend of the hydroxyl radical clearance rates during the 9 h-fermentation. These findings highlight the promising industrial application of fermentation of the plant-based materials with Lactiplantibacillus and Saccharomyces species to improve the biological properties.

Deciphering early human pancreas development at the single-cell level.

Understanding pancreas development can provide clues for better treatments of pancreatic diseases. However, the molecular heterogeneity and developmental trajectory of the early human pancreas are poorly explored. Here, we performed large-scale single-cell RNA sequencing and single-cell assay for transposase accessible chromatin sequencing of human embryonic pancreas tissue obtained from first-trimester embryos. We unraveled the molecular heterogeneity, developmental trajectories and regulatory networks of the major cell types. The results reveal that dorsal pancreatic multipotent cells in humans exhibit different gene expression patterns than ventral multipotent cells. Pancreato-biliary progenitors that generate ventral multipotent cells in humans were identified. Notch and MAPK signals from mesenchymal cells regulate the differentiation of multipotent cells into trunk and duct cells. Notably, we identified endocrine progenitor subclusters with different differentiation potentials. Although the developmental trajectories are largely conserved between humans and mice, some distinct gene expression patterns have also been identified. Overall, we provide a comprehensive landscape of early human pancreas development to understand its lineage transitions and molecular complexity.

Multidisciplinary considerations of fairness in medical AI: A scoping review.

INTRODUCTION: Artificial Intelligence (AI) technology has been developed significantly in recent years. The fairness of medical AI is of great concern due to its direct relation to human life and health. This review aims to analyze the existing research literature on fairness in medical AI from the perspectives of computer science, medical science, and social science (including law and ethics). The objective of the review is to examine the similarities and differences in the understanding of fairness, explore influencing factors, and investigate potential measures to implement fairness in medical AI across English and Chinese literature. METHODS: This study employed a scoping review methodology and selected the following databases: Web of Science, MEDLINE, Pubmed, OVID, CNKI, WANFANG Data, etc., for the fairness issues in medical AI through February 2023. The search was conducted using various keywords such as "artificial intelligence," "machine learning," "medical," "algorithm," "fairness," "decision-making," and "bias." The collected data were charted, synthesized, and subjected to descriptive and thematic analysis. RESULTS: After reviewing 468 English papers and 356 Chinese papers, 53 and 42 were included in the final analysis. Our results show the three different disciplines all show significant differences in the research on the core issues. Data is the foundation that affects medical AI fairness in addition to algorithmic bias and human bias. Legal, ethical, and technological measures all promote the implementation of medical AI fairness. CONCLUSIONS: Our review indicates a consensus regarding the importance of data fairness as the foundation for achieving fairness in medical AI across multidisciplinary perspectives. However, there are substantial discrepancies in core aspects such as the concept, influencing factors, and implementation measures of fairness in medical AI. Consequently, future research should facilitate interdisciplinary discussions to bridge the cognitive gaps between different fields and enhance the practical implementation of fairness in medical AI.

Phosphatidylinositol 3 kinase inhibitor-related pneumonitis: a systematic review and meta-analysis.

INTRODUCTION: Serious phosphatidylinositol 3 kinase (PI3K) inhibitor-related pneumonitis has raised clinical concerns, and integrated data for this condition are lacking. METHODS: Randomized controlled trials (RCTs) comparing PI3K inhibitor therapy with control treatments from electronic databases and registrations were searched from inception to 1 April 20231 April 2023seven1 April 2023. The outcomes of our study were the incidence and risk of all-grade and grade ≥ 3 PI3K inhibitor-associated pneumonitis compared with controls. RESULTS: The meta-analysis included 13 studies comprising 3916 patients. The incidence of all-grade and grade ≥ 3 pneumonitis was 3.7% (82/2210) and 3.0% (35/1162) in patients treated with PI3K inhibitors. PI3K inhibitors significantly increased the risk of all-grade and grade ≥ 3 pneumonitis compared with controls (RR 5.63, 95% CI [2.97, 10.65], P < 0.00001; RR 6.85, 95% CI [2.45, 19.11], P = 0.0002, respectively) with no significant heterogeneity across studies. In terms of different PI3K inhibitors, copanlisib and idelalisib significantly increased the risk of pneumonitis compared to controls (RR 4.99, 95% CI [1.19, 21.01], P = 0.03; RR 5.53, 95% CI [2.35, 13.01], P < 0.0001, respectively). CONCLUSION: PI3K inhibitors significantly increased the risk of pneumonitis compared with controls, and most cases are severe or even life-threatening. PROSPERO REGISTRATION NUMBER: CRD42022318878.

Enhanced microorganism attachment and flavin excretion in microbial fuel cells via an N,S-codoped carbon microflower anode.

Commonly used dense arrays of nanomaterials on carbon cloth (CC) are not suitable to accommodate microorganisms in microbial fuel cells (MFCs) due to their unmatched size. To simultaneously enrich exoelectrogens and accelerate the extracellular electron transfer (EET) process, SnS2 nanosheets were selected as sacrificial templates to prepare binder-free N,S-codoped carbon microflowers (N,S-CMF@CC) by polymer coating and pyrolysis. N,S-CMF@CC showed a cumulative total charge of 125.70C/m2, approximately 2.11 times higher than that of CC, indicating its better electricity storage capacity. Moreover, the interface transfer resistance and diffusion coefficient in bioanodes were 42.68 Ω and 9.27 × 10-10 cm2/s, respectively, superior to CC (141.3 Ω and 1.06 × 10-11 cm2/s). Remarkably, N,S-codoped carbon microflowers excreted more flavin than CC, as confirmed by continuous fluorescence monitoring. Biofilm and 16S rRNA gene sequence analysis revealed that exoelectrogens were enriched, and nanoconduits were generated on the N,S-CMF@CC anode. In particular, flavin excretion was also promoted on our hierarchical electrode, effectively driving the EET process. MFCs equipped with the N,S-CMF@CC anode could deliver a power density of 2.50 W/m2, coulombic efficiency of 22.77 %, and chemical oxygen demand (COD) removal amount of 90.72 mg/L/d, higher than that of bare CC. These findings not only demonstrate that our anode is capable of solving the cell enrichment issue, but it may also increase EET rates by bound flavin with outer membrane c-type cytochromes (OMCs) to simultaneously boost the power generation and wastewater treatment performance of MFCs.

Comparative analysis of absent in melanoma 2-inflammasome activation in Francisella tularensis and Francisella novicida.

Francisella tularensis is a highly virulent Gram-negative bacterium that causes the fatal zoonotic disease tularemia. The mechanisms and signaling pathways leading to the absent in melanoma 2 (Aim2) inflammasome activation have been elegantly elucidated using Francisella novicida as a model. Although not pathogenic for humans, F. novicida can cause tularemia in mice, and the inflammatory response it triggers is the polar opposite to that observed in mice infected with F. tularensis strains. This study aimed to understand the mechanisms of Aim2 inflammasome activation in F. tularensis-infected macrophages. The results reveal that macrophages infected with the F. tularensis live vaccine strain (LVS) induce lower levels of Aim2-dependent IL-1ß than those infected with F. novicida. The suppression/weak activation of Aim2 in F. tularensis LVS-infected macrophages is due to the suppression of the cGAS-STING DNA-sensing pathway. Furthermore, the introduction of exogenous F. tularensis LVS DNA into the cytosol of the F. tularensis LVS-infected macrophages, alone or in conjunction with a priming signal, failed to restore IL-1ß levels similar to those observed for F. novicida-infected macrophages. These results indicated that, in addition to the bacterial DNA, DNA from some other sources, specifically from the damaged mitochondria, might contribute to the robust Aim2-dependent IL-1ß levels observed in F. novicida-infected macrophages. The results indicate that F. tularensis LVS induces mitophagy that may potentially prevent the leakage of mitochondrial DNA and the subsequent activation of the Aim2 inflammasome. Collectively, this study demonstrates that the mechanisms of Aim2 inflammasome activation established for F. novicida are not operative in F. tularensis.

Cost-effectiveness of endovascular thrombectomy with alteplase versus endovascular thrombectomy alone for acute ischemic stroke secondary to large vessel occlusion.

BACKGROUND: Recent randomized trials have suggested that endovascular thrombectomy (EVT) alone may provide similar functional outcomes as the current standard of care, EVT combined with intravenous alteplase treatment, for acute ischemic stroke secondary to large vessel occlusion. We conducted an economic evaluation of these 2 therapeutic options. METHODS: We constructed a decision analytic model with a hypothetical cohort of 1000 patients to assess the cost-effectiveness of EVT with intravenous alteplase treatment versus EVT alone for acute ischemic stroke secondary to large vessel occlusion from both the societal and public health care payer perspectives. We used studies and data published in 2009-2021 for model inputs, and acquired cost data for Canada and China, representing high- and middle-income countries, respectively. We calculated incremental cost-effectiveness ratios (ICERs) using a lifetime horizon and accounted for uncertainty using 1-way and probabilistic sensitivity analyses. All costs are reported in 2021 Canadian dollars. RESULTS: In Canada, the difference in quality-adjusted life-years (QALYs) gained between EVT with alteplase and EVT alone was 0.10 from both the societal and health care payer perspectives. The difference in cost was $2847 from a societal perspective and $2767 from the payer perspective. In China, the difference in QALYs gained was 0.07 from both perspectives, and the difference in cost was $1550 from the societal perspective and $1607 from the payer perspective. One-way sensitivity analyses showed that the distributions of modified Rankin Scale scores at 90 days after stroke were the most influential factor on ICERs. For Canada, compared to EVT alone, the probability that EVT with alteplase would be cost-effective at a willingness-to-pay threshold of $50 000 per QALY gained was 58.7% from a societal perspective and 58.4% from a payer perspective. The corresponding values for at a willingness-to-pay threshold of $47 185 (3 times the Chinese gross domestic product per capita in 2021) were 65.2% and 67.4%. INTERPRETATION: For patients with acute ischemic stroke due to large vessel occlusion eligible for immediate treatment with both EVT alone and EVT with intravenous alteplase treatment, it is uncertain whether EVT with alteplase is cost-effective compared to EVT alone in Canada and China.

Manganese triggers persistent activation of the integrated stress response by inhibition of SIRT1 on deacetylation of GADD34.

Overexposure to manganese (Mn) is conducive to neurodegenerative diseases and neuronal injury. Persistent activation of the integrated stress response (ISR) has a substantial impact on the etiology of neurodegenerative disorders by interfering with intracellular homeostasis. Nevertheless, the precise mechanism through which ISR engages in Mn-related neurotoxicity remains unclear. Sirtuin 1 (SIRT1), a typical NAD+-dependent protein deacetylase, which is known to participate in Mn-induced neuronal damage. Therefore, the aim of our study was to clarify how SIRT1 regulates persistent ISR activation in mouse hippocampal neuronal cells (HT-22 cells) exposed to various concentrations of Mn. We discovered that persistent ISR activation was engaged in Mn-triggered mitochondrial and exogenous apoptotic signaling pathways, which was attributed to the excessive phosphorylation of eukaryotic translation initiation factor 2α (eIF2α). Growth arrest and DNA damage-inducible protein 34 (GADD34) is known to be responsible for down-regulating the phosphorylation of eIF2α. However, Mn promoted GADD34 protein expression and its acetylation level. We further investigated the effect of SIRT1 on the acetylation of GADD34 by overexpressing and silencing SIRT1. We discovered that SIRT1 activation significantly declined the acetylation level of GADD34, thus alleviating persistent ISR activation-mediated neuronal apoptosis in HT-22 cells-treated with Mn. In summary, these results suggested that Mn induced persistent activation of the ISR by inhibition of SIRT1 on deacetylation of GADD34.