Multidimensional Electrochemistry Decodes the Operando Mechanism of Hydrogen Oxidation.

Being an efficient approach to the utilization of hydrogen energy, the hydrogen oxidation reaction (HOR) is of particular significance in the current carbon-neutrality time. Yet the mechanistic picture of the HOR is still blurred, mostly because the elemental steps of this reaction are rapid and highly entangled, especially when deviating from the thermodynamic equilibrium state. Here we report a strategy for decoding the HOR mechanism under operando conditions. In addition to the wide-potential-range I-V curves obtained using gas diffusion electrodes, we have applied the AC impedance spectroscopy to provide independent and complementary kinetic information. Combining multidimensional data sources has enabled us to fit, in mathematical rigor, the core kinetic parameter set in a 5-D data space. The reaction rate of the three elemental steps (Tafel, Heyrovsky, and Volmer reactions), as a function of the overpotential, can thus be distilled individually. Such an undocumented kinetic picture unravels, in detail, how the HOR is controlled by the elemental steps on polarization. For instance, at low polarization region, the Heyrovsky reaction is relatively slow and can be ignored; but at high polarization region, the Heyrovsky reaction will surpass the Tafel reaction. Additionally, the Volmer reaction has been the fastest within overpotentials of interest. Our findings not only offer a better understanding of the HOR mechanism, but also lay the foundation for the development of improved hydrogen energy utilization systems.

Illness perception profile among cancer patients and its influencing factors: A cross-sectional study.

PURPOSE: The purpose of this study was to explore latent profiles of illness perception among cancer patients and its influencing factors. METHODS: This study was a cross-sectional study adopting convenience sampling to select cancer patients from two hospitals in China. A total of 286 patients completed Brief Illness Perception Questionnaire, Post-traumatic Growth Inventory, Fear of Disease Progression Questionnaire and Psychosocial Adjustment to Illness Scale. Latent profile analysis and multiple linear regression were performed to explore the subgroups and factors influencing classification. RESULTS: Three subgroups were identified, which were labelled as "Moderate Illness Perception Group" (16.8%; C1), "High Illness Perception with Heightened Concerns Group" (68.5%; C2) and "High Resilience and Low Symptomatic Impact Group" (14.7%; C3). Specifically, "Normal", "Mild symptom" and "Bed time during the day <50%" of "Functional Status" were more associated with C3. "Worker", "Farmer" and "Self-employed" were more associated with C1 and C2. Patients who had more "knowledge of the disease" were more associated with C2 and C3, who had less "post-traumatic growth" were more associated with C1, and who had less "fear of disease progression" and more "psychosocial adjustment" were more associated with C3 (all P < 0.05). CONCLUSIONS: There was significant variability of illness perception among three subgroups of cancer patients, which emphasized the complexity of psychological condition. The insights derived from these distinct profiles enables tailored interventions and patient-centered communication strategies. However, integrating objective measures or biomarkers is needed to complement self-reported data.

Two-Dimensional Ga2O3/C Nanosheets as Durable and High-Rate Anode Material for Lithium Ion Batteries.

The self-healing feature of gallium (Ga) is unique, making Ga-based materials attract attention for their potential to solve the anode pulverization issue of lithium ion batteries. In this work, a hierarchical two-dimensional (2D) Ga2O3/C structure has been synthesized by a facile NaCl template method. Ga2O3 nanoparticles (3.8 nm) are uniformly embedded in 2D carbon nanosheets. The long horizontal length of the carbon nanosheets (10 µm) provides long-range electron conductivity, and the thin vertical thickness (75 nm) shortens the Li ion diffusion path. Benefited from the integrated 2D structure and the high electron conductivity, the obtained 2D Ga2O3/C nanosheets exhibit excellent overall performance, including high lithium storage capacity (1026 mAh g-1 at 0.5 A g-1), high rate capability (378 mAh g-1 at 10.0 A g-1), and high cyclability (500 cycles at 0.5 A g-1). The lithiation/delithiation mechanism of 2D Ga2O3/C has been further studied with combined electrochemical and ex situ X-ray diffraction methods.

Hydrazine-Assisted Liquid Exfoliation of MoS2 for Catalytic Hydrodeoxygenation of 4-Methylphenol.

A simple but effective method to exfoliate bulk MoS2 in a range of solvents is presented for the preparation of colloid flakes consisted of one to a few molecular layers by application of ultrasonic treatment in N2 H4 . Their high yield in solution and exposure of more active surface sites allows the synthesis of corresponding solid catalysts with remarkably high activity in hydrodeoxygenation of 4-methylphenol and this method can also be applied to other two dimensional materials.

Microglial P2Y12 deficiency/inhibition protects against brain ischemia.

OBJECTIVE: Microglia are among the first immune cells to respond to ischemic insults. Triggering of this inflammatory response may involve the microglial purinergic GPCR, P2Y12, activation via extracellular release of nucleotides from injured cells. It is also the inhibitory target of the widely used antiplatelet drug, clopidogrel. Thus, inhibiting this GPCR in microglia should inhibit microglial mediated neurotoxicity following ischemic brain injury. METHODS: Experimental cerebral ischemia was induced, in vitro with oxygen-glucose deprivation (OGD), or in vivo via bilateral common carotid artery occlusion (BCCAO). Genetic knock-down in vitro via siRNA, or in vivo P2Y12 transgenic mice (P2Y12-/- or P2Y12+/-), or in vivo treatment with clopidogrel, were used to manipulate the receptor. Neuron death, microglial activation, and microglial migration were assessed. RESULTS: The addition of microglia to neuron-astrocyte cultures increases neurotoxicity following OGD, which is mitigated by microglial P2Y12 deficiency (P<0.05). Wildtype microglia form clusters around these neurons following injury, which is also prevented in P2Y12 deficient microglia (P<0.01). P2Y12 knock-out microglia migrated less than WT controls in response to OGD-conditioned neuronal supernatant. P2Y12 (+/-) or clopidogrel treated mice subjected to global cerebral ischemia suffered less neuronal injury (P<0.01, P<0.001) compared to wild-type littermates or placebo treated controls. There were also fewer microglia surrounding areas of injury, and less activation of the pro-inflammatory transcription factor, nuclear factor Kappa B (NFkB). INTERPRETATION: P2Y12 participates in ischemia related inflammation by mediating microglial migration and potentiation of neurotoxicity. These data also suggest an additional anti-inflammatory, neuroprotective benefit of clopidogrel.

Glucose and NADPH oxidase drive neuronal superoxide formation in stroke.

OBJECTIVE: Hyperglycemia has been recognized for decades to be an exacerbating factor in ischemic stroke, but the mechanism of this effect remains unresolved. Here, we evaluated superoxide production by neuronal nicotinamide adenine dinucleotide phosphate (NADPH) oxidase as a possible link between glucose metabolism and neuronal death in ischemia-reperfusion. METHODS: Superoxide production was measured by the ethidium method in cultured neurons treated with oxygen-glucose deprivation and in mice treated with forebrain ischemia-reperfusion. The role of NADPH oxidase was examined using genetic disruption of its p47(phox) subunit and with the pharmacological inhibitor apocynin. RESULTS: In neuron cultures, postischemic superoxide production and cell death were completely prevented by removing glucose from the medium, by inactivating NADPH oxidase, or by inhibiting the hexose monophosphate shunt that generates NADPH from glucose. In murine stroke, neuronal superoxide production and death were decreased by the glucose antimetabolite 2-deoxyglucose and increased by high blood glucose concentrations. Inactivating NADPH oxidase with either apocynin or deletion of the p47(phox) subunit blocked neuronal superoxide production and negated the deleterious effects of hyperglycemia. INTERPRETATION: These findings identify glucose as the requisite electron donor for reperfusion-induced neuronal superoxide production and establish a previously unrecognized mechanism by which hyperglycemia can exacerbate ischemic brain injury.

Acetylcholine receptor gamma-subunits mRNA isoforms expressed in denervated rat muscle.

The fetal acetylcholine (ACh) receptor, composed of the alphabetagammadelta subunits, is expressed in fetal, neonatal, and denervated muscle. Single-channel recording has revealed three kinetically distinct classes in neonatal and denervated muscle, suggesting that at least three forms of the gamma-subunit are required. To account for the kinetic classes observed, we compared the messenger ribonucleic acid (mRNA) forms expressed in neonatal and denervated muscle using reverse transcriptase polymerase chain reaction, cloning, and RNAse protection assays. We found five novel forms arising from alternative splicing, which we named gamma5-gamma9. The forms gamma5, gamma6, and gamma7 lack exon 4 and 63-, 89-, and 136 bp of exon 5, respectively. A gamma8 form lacks exons 3 and 4 and 19 bp of exon 5. The last, gamma9, lacks exons 3, 4, and 5. Results indicate that gamma4 predominates in fetal muscle and gamma7 in denervated adult muscle. Some of the gamma-subunit mRNAs found may generate the receptors observed in muscle.

FasL shedding is reduced by hypothermia in experimental stroke.

Protection by mild hypothermia has previously been associated with better mitochondrial preservation and suppression of the intrinsic apoptotic pathway. It is also known that the brain may undergo apoptotic death via extrinsic, or receptor-mediated pathways, such as that triggered by Fas/FasL. Male Sprague-Dawley rats subjected to 2 h middle cerebral artery occlusion with 2 h intraischemic mild hypothermia (33 degrees C) were assayed for Fas, FasL and caspase-8 expression. Ischemia increased Fas, but decreased FasL by approximately 50-60% at 6 and 24 h post-insult. Mild hypothermia significantly reduced expression of Fas and processed caspase-8 both by approximately 50%, but prevented ischemia-induced FasL decreases. Fractionation revealed that soluble/shed FasL (sFasL) was decreased by hypothermia, while membrane-bound FasL (mFasL) increased. To more directly assess the significance of the Fas/FasL pathway in ischemic stroke, primary neuron cultures were exposed to oxygen glucose deprivation. Since FasL is cleaved by matrix metalloproteinases (MMPs), and mild hypothermia decreases MMP expression, treatment with a pan-MMP inhibitor also decreased sFasL. Thus, mild hypothermia is associated with reduced Fas expression and caspase-8 activation. Hypothermia prevented total FasL decreases, and most of it remained membrane-bound. These findings reveal new observations regarding the effect of mild hypothermia on the Fas/FasL and MMP systems.

Anti-inflammatory effects of the 70 kDa heat shock protein in experimental stroke.

The 70-kDa heat shock protein (Hsp70) is involved in protecting the brain from a variety of insults including stroke. Although the mechanism has been largely considered to be because of its chaperone functions, recent work indicates that Hsp70 also modulates inflammatory responses. To explore how and whether Hsp70 regulate immune responses in brain ischemia, mice overexpressing Hsp70 (Hsp Tg) were subjected to 2 h middle cerebral artery occlusion, followed by 24 h reperfusion. Parallel experiments were performed using a brain inflammation model. Hsp Tg microglia cocultured with astrocytes were used to evaluate the direct effects of Hsp70 on cytotoxicity of microglia. Compared with wild-type (Wt) littermates, Hsp Tg mice showed decreased infarct size and improved neurological deficits. The number of activated microglia/macrophages were also reduced in ischemic brains of Hsp Tg mice. Similar observations were made in a model of brain inflammation that does not result in brain cell death. Overexpression of Hsp70 in microglia completely prevented microglia-induced cytotoxicity to astrocytes. Activation of the inflammatory transcription factor, nuclear factor-kappaB (NF-kappaB) was inhibited significantly in Hsp Tg mice and microglia. This was associated with decreased phosphorylation of NF-kappaB inhibitor protein, IkappaBalpha, and decreased expression of several NFkappaB-regulated genes. Co-immunoprecipitation studies revealed an interaction of Hsp70 with NF-kappaB and IkappaBalpha, but not with IkappaB kinase, IKKgamma, suggesting that Hsp70 binds to the NF-kappaB:IkappaB complex preventing IkappaB phosphorylation by IKK. The findings of the present work establish an anti-inflammatory role for Hsp70 in the context of brain ischemia as a novel mechanism of protection.

Defective neuromuscular synaptogenesis in mice expressing constitutively active ErbB2 in skeletal muscle fibers.

We overexpressed a constitutively active form of the neuregulin receptor ErbB2 (CAErbB2) in skeletal muscle fibers in vivo and in vitro by tetracycline-inducible expression. Surprisingly, CAErbB2 expression during embryonic development was lethal and impaired synaptogenesis yielding a phenotype with loss of synaptic contacts, extensive axonal sprouting, and diffuse distribution of acetylcholine receptor (AChR) transcripts, reminiscent of agrin-deficient mice. CAErbB2 expression in cultured myotubes inhibited the formation and maintenance of agrin-induced AChR clusters, suggesting a muscle- and not a nerve-origin for the defect in CAErbB2-expressing mice. Levels of tyrosine phosphorylated MuSK, the signaling component of the agrin receptor, were similar, while tyrosine phosphorylation of AChRbeta subunits was dramatically reduced in CAErbB2-expressing embryos relative to controls. Thus, a gain-of-function manipulation of ErbB2 signaling pathways renders an agrin-deficient-like phenotype that uncouples MuSK and AChR tyrosine phosphorylation.