Miracle-dz/UniFAR-FTUs huggingface dataset:
A nitrogen and fluorine enriched Fe/Fe3C@C oxygen reduction reaction electrocatalyst for anion/proton exchange membrane fuel cells.

Nitrogen-doped carbon-encapsulated non-noble metals are promising electrocatalytic alternatives to Pt for the oxygen reduction reaction (ORR). Herein, we describe the efficient synthesis of nitrogen- and fluorine-doped carbon-encapsulated Fe/Fe3C (NFC@Fe/Fe3C) crystals from a Fe-poly(aniline-fluoro-aniline) co-polymer and demonstrate their use as efficient ORR electrocatalysts in acidic and alkaline environments. X-ray diffraction patterns, scanning electron microscopy, transmission electron microscopy, Raman spectra, and X-ray photoelectron spectroscopy are used to determine the structural properties of NFC@Fe/Fe3C. Of the NFC@Fe/Fe3C catalysts, NFC@Fe/Fe3C-9 demonstrates superior ORR electrocatalytic activity in both alkaline and acidic environments. NFC@Fe/Fe3C-9 follows a four-electron-transfer ORR pathway in alkaline and acidic media. Under alkaline conditions, NFC@Fe/Fe3C-9 displays a half-wave potential (E1/2) as 0.870 V, which is 16 mV higher than that of Pt/C, and its durability decay is 26 mV over 50 000 cycles. In acidic medium, the NFC@Fe/Fe3C-9 electrode shows inferior ORR performance than does Pt/C, but it is more durable, with only 27 mV decay over 30 000 cycles. A single cell performance of NFC@Fe/Fe3C-9 was tested with a proton-exchange membrane fuel cells (PEMFC) and an anion-exchange membrane fuel cell (AEMFC) with an active area of 5 cm2. The PEMFC single cell exhibits the maximum power density of 237 mW cm-2 with a back pressure of 250 kPa, while the AEMFC delivers a maximum power density of 96 mW cm-2 without back pressure.
A spatial ecology study in a high‐diversity host community to understand blood‐feeding behaviour in Phlebotomus sandfly vectors of Leishmania

Molecular studies indicate that Phlebotomine sandflies (Diptera: Psychodidae) blood feed on many vertebrate species, of which only a few are proven parasite reservoirs. Investigating sandfly vector feeding preferences is therefore important and requires taking into account the availability and accessibility of host species. In terms of the latter, it is necessary to consider the metabolic cost to the insect of reaching the host and moving on to a suitable breeding site. The present study used statistical modelling to compare the feeding patterns of Phlebotomus perniciosus (n = 150), Phlebotomus papatasi (n = 35) and Phlebotomus ariasi (n = 7) on each of an average of 30 host species in a wildlife park in Murcia, Spain. Sandfly feeding movement costs were estimated as a function of the distance and altitude gradients saved by the insect, assuming that they displayed ‘site fidelity’. Most (87%) engorged females were caught <100 m from the host on which they had fed. Although the percentage of bloodmeals was highest on fallow deer (Dama dama) (30%) and red deer (Cervus elaphus) (26%), the predicted feeding probability after considering movement cost was highest for red deer and common eland (Taurotragus oryx), and positively associated with host census. These results suggest that, under similar circumstances, sandflies prefer to feed on some host species more than on others.
A Redox-Sensitive Thiol in Wis1 Modulates the Fission Yeast Mitogen-Activated Protein Kinase Response to H2O2 and Is the Target of a Small Molecule

Oxidation of a highly conserved cysteine (Cys) residue located in the kinase activation loop of mitogen-activated protein kinase kinases (MAPKK) inactivates mammalian MKK6. This residue is conserved in the fission yeast Schizosaccharomyces pombe MAPKK Wis1, which belongs to the H2O2-responsive MAPK Sty1 pathway. Here, we show that H2O2 reversibly inactivates Wis1 through this residue (C458) in vitro. ABSTRACT Oxidation of a highly conserved cysteine (Cys) residue located in the kinase activation loop of mitogen-activated protein kinase kinases (MAPKK) inactivates mammalian MKK6. This residue is conserved in the fission yeast Schizosaccharomyces pombe MAPKK Wis1, which belongs to the H2O2-responsive MAPK Sty1 pathway. Here, we show that H2O2 reversibly inactivates Wis1 through this residue (C458) in vitro. We found that C458 is oxidized in vivo and that serine replacement of this residue significantly enhances Wis1 activation upon addition of H2O2. The allosteric MAPKK inhibitor INR119, which binds in a pocket next to the activation loop and C458, prevented the inhibition of Wis1 by H2O2 in vitro and significantly increased Wis1 activation by low levels of H2O2 in vivo. We propose that oxidation of C458 inhibits Wis1 and that INR119 cancels out this inhibitory effect by binding close to this residue. Kinase inhibition through the oxidation of a conserved Cys residue in MKK6 (C196) is thus conserved in the S. pombe MAPKK Wis1.
Costs and factors associated with heart failure following kidney transplantation – a single‐center retrospective cohort study

The number of adults with heart failure (HF) will increase by ~50% between 2012 and 2030. Among kidney transplant recipients, HF accounts for 16% of all post‐transplant admissions. We describe the burden of HF and predictors of healthcare utilization following kidney transplantation. We retrospectively identified adults who underwent kidney transplantation at our institution (01/2007–12/2017). Data were acquired from electronic health records, with healthcare utilization obtained from a statewide database. The HF incidence rate and prevalence were estimated for each year, total charges for HF and non‐HF patients were compared, and logistic regression was employed for a 3‐year predictive model of healthcare utilization associated with HF. Among 1731 kidney transplant recipients, the post‐transplant HF incidence rate ranged from 1.91 (year 3) to 6.80 (year 10) per 100 person‐years, while the prevalence increased from 31.7% (year 1) to 48.1% (year 10). Median charges were $75 837 (HF) compared to $42 940 (non‐HF) per person‐year (P < 0.001). Pretransplant HF [odds ratio (OR) = 3.12] and an eGFR < 45 (OR = 4.73) were the strongest predictors of HF encounters (P < 0.05 for both). We observed a high and increasing prevalence of HF, which was associated with twice the costs. Kidney transplant recipients would benefit from interventions aimed at mitigating HF risk factors.
Foodborne Klebsiella pneumoniae: virulence potential, antibiotic resistance and risks to food safety.

Gastrointestinal carriage of Klebsiella pneumoniae is a predisposing factor for liver abscess in several Asian countries. To determine whether hypervirulent K. pneumoniae in the gut may be transmitted through food, we screened a range of raw and ready-to-eat (RTE) retail food by culture and recovered K. pneumoniae in 21% (147/698) of samples tested. Based on polymerase chain reactions (PCR), no K. pneumoniae isolates carried the rmpA gene linked to community-acquired pyogenic liver abscess, providing no evidence of a link between food and the liver disease. However, phenotypic resistance to multiple antibiotic classes was seen through disk diffusion tests and carriage of genetic elements ( wcaG , capsule types K1, K2, K54) associated with increased virulence (8%, 11/147) were observed by PCRs. Multidrug-resistant (MDR) isolates were from raw vegetables, chicken/pork livers, and a RTE poultry dish; one MDR K. pneumoniae isolate from raw beansprouts was resistant to a 3rd generation cephalosporin (ceftriaxone). While K. pneumoniae may be present in food without causing harm, we found isolates belonging to the K1 capsular serotype co-existing with the wcaG gene, once also conferring multidrug resistance. K. pneumoniae that carry antibiotic resistance genes, regardless of pathogenicity, may increase the available genetic pool of resistance along the food chain. Hygienic food handling practices are necessary to lower risks of acquiring K. pneumoniae and other opportunistic pathogens.
Subinhibitory Concentrations of Mupirocin Stimulate Staphylococcus aureus Biofilm Formation by Upregulating cidA

Previous studies have shown that the administration of antibiotics at subinhibitory concentrations stimulates biofilm formation by the majority of multidrug-resistant Staphylococcus aureus (MRSA) strains. Here, we investigated the effect of subinhibitory concentrations of mupirocin on biofilm formation by the community-associated (CA) mupirocin-sensitive MRSA strain USA300 and the highly mupirocin-resistant clinical S. aureus SA01 to SA05 isolates. ABSTRACT Previous studies have shown that the administration of antibiotics at subinhibitory concentrations stimulates biofilm formation by the majority of multidrug-resistant Staphylococcus aureus (MRSA) strains. Here, we investigated the effect of subinhibitory concentrations of mupirocin on biofilm formation by the community-associated (CA) mupirocin-sensitive MRSA strain USA300 and the highly mupirocin-resistant clinical S. aureus SA01 to SA05 isolates. We found that mupirocin increased the ability of MRSA cells to attach to surfaces and form biofilms. Confocal laser scanning microscopy (CLSM) demonstrated that mupirocin treatment promoted thicker biofilm formation, which also correlated with the production of extracellular DNA (eDNA). Furthermore, quantitative real-time PCR (RT-qPCR) results revealed that this effect was largely due to the involvement of holin-like and antiholin-like proteins (encoded by the cidA gene), which are responsible for modulating cell death and lysis during biofilm development. We found that cidA expression levels significantly increased by 6.05- to 35.52-fold (P < 0.01) after mupirocin administration. We generated a cidA-deficient mutant of the USA300 S. aureus strain. Exposure of the ΔcidA mutant to mupirocin did not result in thicker biofilm formation than that in the parent strain. We therefore hypothesize that the mupirocin-induced stimulation of S. aureus biofilm formation may involve the upregulation of cidA.
Persistent double strand break accumulation does not precede cell death in an Olaparib-sensitive BRCA-deficient colorectal cancer cell model

Abstract The poly (adenosine diphosphate (ADP)-ribosyl) polymerase inhibitors (PARPi) selectively kill cancer cells with BRCA1 or BRCA2 (BRCA)-mutations. It has been proposed that cell death induction after PARPi depends on unrepaired double strand breaks (DSBs) that accumulate due to the homologous recombination deficiency of BRCA-mutated cells. Such accumulation of DSBs is inferred mainly from the high levels of DNA damage markers like phosphorylated histone H2AX. Herein, we developed a model of isogenic cell lines to show that depletion of BRCA causes PARPi-triggered cell death, replication stress (phosphorylated-H2AX and 53BP1 foci), and genomic instability. However, persistent DSBs accumulation was not detected under the same experimental conditions. Hence, at least in this cellular model, the trigger for cell death in PARPi-treated BRCA-depleted samples is not the accumulation of unrepaired DSBs. Instead, cell death better correlates with a rapid and aberrant resolution of DSBs by error-prone pathways that leads to severe chromosomic aberrations. Therefore, our results suggest that in PARPi-treated BRCA-deficient cells, chromosome aberrations may dually trigger both genomic instability and cell death.
Combination of electrospinning with other techniques for the fabrication of 3D polymeric and composite nanofibrous scaffolds with improved cellular interactions

The development of three-dimensional (3D) scaffolds with physical and chemical topological cues at the macro-, micro-, and nanometer scale is urgently needed for successful tissue engineering applications. 3D scaffolds can be manufactured by a wide variety of techniques. Electrospinning technology has emerged as a powerful manufacturing technique to produce non-woven nanofibrous scaffolds with very interesting features for tissue engineering products. However, electrospun scaffolds have some inherent limitations that compromise the regeneration of thick and complex tissues. By integrating electrospinning and other fabrication technologies, multifunctional 3D fibrous assemblies with micro/nanotopographical features can be created. The proper combination of techniques leads to materials with nano and macro-structure, allowing an improvement in the biological performance of tissue-engineered constructs. In this review, we focus on the most relevant strategies to produce electrospun polymer/composite scaffolds with 3D architecture. A detailed description of procedures involving physical and chemical agents to create structures with large pores and 3D fiber assemblies is introduced. Finally, characterization and biological assays including in vitro and in vivo studies of structures intended for the regeneration of functional tissues are briefly presented and discussed.
Single-nucleus RNA sequencing reveals transcriptional changes of hippocampal neurons in APP23 mouse model of Alzheimer’s disease

ABSTRACT Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that mostly strikes the elderly. However, the exact molecular and cellular pathogenesis of AD, especially the dynamic changes of neurons during disease progression, remains poorly understood. Here we used single-nucleus RNA sequencing (snRNA-seq) to access the transcriptional changes of hippocampal neurons in APP23 mouse model of AD. We performed snRNA-seq using a modified Smart-seq2 technique on 3,280 neuronal nuclei from the hippocampus of young and aged APP23 and control mice and identified four distinct subpopulations. Comparative transcriptional analysis showed multiple changes in different subtypes of hippocampal neurons of APP23 mice in comparison to control mice, as well as the transcriptional changes in these neurons during disease progression. Our findings revealed multiple neuronal subtype-specific transcriptional changes that may lead to targets for future studies of AD. Graphical abstract Single-nucleus RNA-seq for identifying the transcriptional changes in hippocampal neurons of an Alzheimer’s disease mouse model.
Clinical study on the treatment of fatal hepatitis with artificial liver support system

Objective:To observe the clinical curative effects of artificial liver support system(ALSS) and the application of plasma exchange(PE),plasma perfusion(PP) and direct hemoperfusion(DHP) in the treatment of fatal hepatitis.Methods:64 cases served as treatment group and 60 cases as control group,both groups were similar in basic medical treatment,but an additional ALSS was used in the treatment group.PE was to replace each time with the heterogenous,but homeotypical plasma at an equivalent amount of 40 to 60 ml/kg;PP was to replace each time with 100 to 150 ml/kg of plasma;DHP was to replace each time with 170 to 250 ml/kg of the whole blood volume,once every 2 or 7 days until the patient′s condition was improved.Results:168 times of treatment were performed in the treatment group,2 6 times averagely.44 cases survived in the treatment gorup,and the total survival rate was 68 75%;However,in the control group,28 cases survived and the total survival rate was 46 67%. In the treatment group,the survival rate during the early,intermediate and late stages of fatal hepatitis cases respectively were 85 71%,76 47% and 52 17%. PE was applicable in the treatment of various acute toxipathic hepatitis,PP was applicable in the treatment of acute cholestatic hepatitis and DHP was available to reduce NH 3 on the whole,applicable in the treatment of hyperammonemia and hepatic encephalopathy.During the process of treatment,24 times of side effects were found(15 58%),but they were relieved after expectant treatment.Conclusions:The ALSS treatment will effectively remove the pathological compositions,including total bilirubin(TBIL),NH 3,tumor necrosis factorα and endotoxin,out of the liver associated with fatal hepatitis,and it is available to improve the survival rate and reduce the mortality rate in patients with fatal hepatitis.
Effect of Induced Membrane on Guided Bone Regeneration in an Experimental Calvarial Model.

OBJECTIVE The aim of this study was to evaluate the effect of induced membrane on guided bone regeneration and to compare its effect with poly-tetra-flourur-ethylene (PTFE) membrane and collagen membrane. METHODS Sixteen white Vienna rabbits were used for experiments. Initially 1 defect was created on the parietal bone of all animals and cement was placed inside the defects. After 8 weeks, the bone cements were removed, without damaging the induced membrane formed in the defect cavity. And then 2 more defects were created. All defects were filled with xsenogenic graft materials and were covered with newly formed induced membrane, d-PTFE membrane and collagen membrane. Eight animals were sacrificed at 4th week and other 8 animals were sacrificed at 8th week and all bone specimens were histologically evaluated. RESULTS New bone formation and bone marrow ratios were significantly higher in induced membrane and d-PTFE membrane group compared to collagen membrane group (P < 0.05) at 4th week. Mature bone ratios were significantly higher in induced membrane and d-PTFE membrane group compared to collagen membrane group (P < 0.05) at 8th week. The best CD31 value was detected with d-PTFE membrane group at 4th week and with induced membrane at 8th week. CONCLUSION Induced membrane can act as a strong barrier membrane and stimulate bone regeneration. Induced membrane technique can be accepted as a good alternative for the reconstruction of critical size defects in maxillofacial region.
Nociceptin attenuates the escalation of oxycodone self-administration by normalizing CeA–GABA transmission in highly addicted rats

Significance More than 2 million individuals in the United States currently have a substance use disorder that is related to prescription opioid pain relievers. We identified individual differences in oxycodone addiction-like behaviors in outbred heterogenous stock rats with high and low addiction-like behaviors. We found that the downregulation of nociceptin levels in the central nucleus of the amygdala (CeA) may be responsible for hyper–γ-aminobutyric acid (GABA)ergic tone in the CeA that is observed in individuals who develop addiction-like behaviors. The development of small molecules that target the nociceptin system may have therapeutic efficacy for the treatment of opioid use disorder. Approximately 25% of patients who are prescribed opioids for chronic pain misuse them, and 5 to 10% develop an opioid use disorder. Although the neurobiological target of opioids is well known, the molecular mechanisms that are responsible for the development of addiction-like behaviors in some but not all individuals are poorly known. To address this issue, we used a unique outbred rat population (heterogeneous stock) that better models the behavioral and genetic diversity that is found in humans. We characterized individual differences in addiction-like behaviors using an addiction index that incorporates the key criteria of opioid use disorder: escalated intake, highly motivated responding, and hyperalgesia. Using in vitro electrophysiological recordings in the central nucleus of the amygdala (CeA), we found that rats with high addiction-like behaviors (HA) exhibited a significant increase in γ-aminobutyric acid (GABA) transmission compared with rats with low addiction-like behaviors (LA) and naive rats. The superfusion of CeA slices with nociceptin/orphanin FQ peptide (N/OFQ; 500 nM), an endogenous opioid-like peptide, normalized GABA transmission in HA rats. Intra-CeA levels of N/OFQ were lower in HA rats than in LA rats. Intra-CeA infusions of N/OFQ (1 μg per site) reversed the escalation of oxycodone self-administration in HA rats but not in LA rats. These results demonstrate that the downregulation of N/OFQ levels in the CeA may be responsible for hyper-GABAergic tone in the CeA that is observed in individuals who develop addiction-like behaviors. Based on these results, we hypothesize that small molecules that target the N/OFQ system might be useful for the treatment of opioid use disorder.
Temporal Trends in Population-Level Cure of Cancer: The Australian Context

Background: With the improvements in cancer diagnosis and treatment, more patients with cancer are surviving for longer periods than before. This study aims to quantify the proportion cured and median survival time for those who are not cured for major cancers in Australia. Methods: Australian population-based cohort of 2,164,172 cases, ages 15 to 89 years, whose first cancer diagnosis between 1982 and 2014 was one of 22 leading cancers, were followed up to December 2014. Flexible parametric cure models were used to estimate the proportion cured and median survival time for those uncured by age, sex, and spread of disease, and temporal trends in these measures. Results: Cure estimates could be generated for 19 of the 22 cancer types. The unadjusted proportion cured ranged from 5.0% for pancreatic cancer to 90.0% for melanoma. Median survival time for those uncured ranged from 0.35 years for pancreatic cancer to 6.05 years for prostate cancer. Cancers were divided into four groups according to their proportion cured in the 1980s and the degree of improvement over 28 years. Esophageal, stomach, pancreatic, liver, gallbladder, lung, and brain cancer had lower proportion cured and smaller improvements over time. Conclusions: For cancers with poor survival in which little has changed over time either in prolonging life or achieving statistical cure, efforts should be focused on reducing the prevalence of known risk factors and earlier detection, thereby enabling more effective treatment. Impact: Cure models provide unique insights into whether survival improvements are due to prolonging life or through curing the disease.
Surgery/Anesthesia disturbs mitochondrial fission/fusion dynamics in the brain of aged mice with postoperative delirium

Postoperative delirium (POD) is a common complication following surgery and anesthesia (Surgery/Anesthesia). Mitochondrial dysfunction, which is demonstrated by energy deficits and excessively activated oxidative stress, has been reported to contribute to POD. The dynamic balance between mitochondrial fusion and fission processes is critical in regulating mitochondrial function. However, the impact of Surgery/Anesthesia on mitochondrial fusion/fission dynamics remains unclear. Here, we evaluate the effects of laparotomy under 1.4% isoflurane anesthesia for 2 hours on mitochondrial fission/fusion dynamics in the brain of aged mice. Mice in Surgery/Anesthesia group showed unbalanced fission/fusion dynamics, with decreased DISC1 expression and increased expression of Drp1 and Mfn2 in the mitochondrial fraction, leading to excessive mitochondrial fission and disturbed mitochondrial morphogenesis in the hippocampus and prefrontal cortex. In addition, surgical mice presented mitochondrial dysfunction, demonstrated by abnormally activated oxidative stress (increased ROS level, decreased SOD level) and energy deficits (decreased levels of ATP and MMP). Surgery/Anesthesia also decreased the expression of neuronal/synaptic plasticity-related proteins such as PSD-95 and BDNF. Furthermore, Surgery/Anesthesia induced delirium-like behavior in aged mice. In conclusion, Surgery/Anesthesia disturbed mitochondrial fission/fusion dynamics and then impaired mitochondrial function in the brain of aged mice; these effects may be involved in the underlying mechanism of POD.