Surface sites of extensively exposed basal planes of MoS2 monolayer nanosheets, prepared via BuLi exfoliation of MoS2, have been doped with transition metal atoms for the first time to produce 2D ...monolayer catalysts used for the electrochemical hydrogen evolution reaction (HER). Their HER activity is significantly higher than the corresponding thin and bulk MoS2 layers. HAADF-STEM images show direct proof that single transition metal atoms reside at the surface basal sites, which subtly modify the electro-catalytic activity of the monolayer MoS2, dependent on their electronic and stereospecific properties. It is found that these dopants play an important role in tuning the hydrogen adsorption enthalpies of the exposed surface S atoms and Mo atoms in HER. We report electrochemical testing, characterization and computational modelling and demonstrate that Co can significantly enhance the HER activity by the dominant Co–S interaction, whereas Ni substantially lowers the HER rate due to the Ni–Mo interaction at the same basal site. The two transition metal dopants show opposite doping behavior despite the fact that they are neighbors in the periodic table.
2D nanosheets give enhanced surface area to volume ratios in particle morphology and they can also provide defined surface sites to disperse foreign atoms. Placing atoms of catalytic interest on 2D ...nanosheets as Single Atom Catalysts (SAC) represents one of the novel approaches due to their unique but tunable electronic and steric characteristics. Here in this mini-review, we particularly highlight some recent and important developments on heteroatom doped MoS
2
nanosheets (SAC-MoS
2
) as catalysts for the electrochemical hydrogen evolution reaction (HER) from water, which could lead to opening up to a flagship of important renewable technologies in future. It is shown that the nature of dopants, doping positions and the polytypes of MoS
2
nanosheets are the determining factors in the overall catalytic abilities of these functionalised nanosheets. This may serve to obtain atomic models which lead to further understanding of the 'metal-support interaction' in catalysis.
2D nanosheets give enhanced surface area to volume ratios in particle morphology and they can also provide defined surface sites to disperse foreign atoms.
There has been an intense research effort to develop 2-H MoS2 based catalysts to reduce or eliminate the use of Pt/C at higher metal loading for the hydrogen evolution reaction (HER) in catalytic ...hydrolysis of water, which enables the capture of renewable energy sources as fuel and chemical. However, the study of its uncommon polymorph, 1T-MoS2, and particularly the doping effect with transition metal (TM) is rather limited due to the instability of this phase. Here, we report a simple ambient temperature modification method using sonication to dope the single layer 1T-SMoS2 with various TM precursors. It is found that 1T-SMoS2 is more active than corresponding 2H-SMoS2 and the inclusion of 3 wt % Pt or Pd can also further enhance the HER activity. STEM-EELS and XAS show that the active single TM atom doping on this surface accounts for the high activity. Kinetic and DFT analyses also illustrate that the metallic nature of 1T-SMoS2 greatly facilitates the proton reduction step from water, rendering it non-rate-limiting in contrast to that of 2H-SMoS2. The inclusion of the TM single doper such as Pd, despite at low loading, can offer the dramatic acceleration of the rate limiting recombination of H to H2. As a result, a bifunctional catalysis for HER over this tailored composite structure is demonstrated that outperforms most reported catalysts in this area.
The SARS-CoV-2 pandemic has resulted in millions of infections, yet the role of host immune responses in early COVID-19 pathogenesis remains unclear. By investigating 17 acute and 24 convalescent ...patients, we found that acute SARS-CoV-2 infection resulted in broad immune cell reduction including T, natural killer, monocyte, and dendritic cells (DCs). DCs were significantly reduced with functional impairment, and ratios of conventional DCs to plasmacytoid DCs were increased among acute severe patients. Besides lymphocytopenia, although neutralizing antibodies were rapidly and abundantly generated in patients, there were delayed receptor binding domain (RBD)- and nucleocapsid protein (NP)-specific T cell responses during the first 3 weeks after symptoms onset. Moreover, acute RBD- and NP-specific T cell responses included relatively more CD4 T cells than CD8 T cells. Our findings provided evidence that impaired DCs, together with timely inverted strong antibody but weak CD8 T cell responses, could contribute to acute COVID-19 pathogenesis and have implications for vaccine development.
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•Acute SARS-CoV-2 infection results in broad immune cell reduction•Both dendritic cells and T cells are functionally impaired•Neutralizing antibodies are rapidly and abundantly generated•RBD- and NP-specific T cells are delayed at the acute stage
COVID-19 is an acute disease caused by SARS-CoV-2 infection. We determine how the immune system responds to SARS-CoV-2 at both acute and convalescent stages. Acute SARS-CoV-2 infection results in broad immune cell reduction and functional impairment. While neutralizing antibodies are rapidly generated, antigen-specific T cells are delayed at the acute stage.
PURPOSE: To investigate the protective mechanisms of an 85 % pure extract of (−) epigallocatechin gallate (EGCG) in the development of fibrosis, oxidative stress and inflammation in a recently ...developed dietary-induced animal model of non-alcoholic fatty liver disease (NAFLD). METHODS: Female Sprague–Dawley rats were fed with either normal rat diet or high-fat diet for 8 weeks to develop NAFLD. For both treatments, rats were treated with or without EGCG (50 mg/kg, i.p. injection, 3 times per week). At the end, blood and liver tissue samples were obtained for histology, molecular, and biochemical analyses. RESULTS: Non-alcoholic fatty liver disease (NAFLD) rats showed significant amount of fatty infiltration, necrosis, fibrosis, and inflammation. This was accompanied by a significant expressional increase in markers for fibrosis, oxidative stress, and inflammation. TGF/SMAD, PI3 K/Akt/FoxO1, and NF-κB pathways were also activated. Treatment with EGCG improved hepatic histology (decreased number of fatty score, necrosis, and inflammatory foci), reduced liver injury (from ~0.5 to ~0.3 of ALT/AST ratio), attenuated hepatic changes including fibrosis (reduction in Sirius Red and synaptophysin-positive stain) with down-regulation in the expressions of key pathological oxidative (e.g. nitrotyrosine formation) and pro-inflammatory markers (e.g. iNOS, COX-2, and TNF-α). EGCG treatment also counteracted the activity of TGF/SMAD, PI3 K/Akt/FoxO1, and NF-κB pathways. Treatment with EGCG did not affect the healthy rats. CONCLUSIONS: Epigallocatechin gallate (EGCG) reduced the severity of liver injury in an experimental model of NAFLD associated with lower concentration of pro-fibrogenic, oxidative stress, and pro-inflammatory mediators partly through modulating the activities of TGF/SMAD, PI3 K/Akt/FoxO1, and NF-κB pathways. Therefore, green tea polyphenols and EGCG are useful supplements in the prevention of NAFLD.
Characterization of the proteome of organelles and subcellular domains is essential for understanding cellular organization and identifying protein complexes as well as networks of protein ...interactions. We established a proteomic mapping platform in live Drosophila tissues using an engineered ascorbate peroxidase (APEX). Upon activation, the APEX enzyme catalyzes the biotinylation of neighboring endogenous proteins that can then be isolated and identified by mass spectrometry. We demonstrate that APEX labeling functions effectively in multiple fly tissues for different subcellular compartments and maps the mitochondrial matrix proteome of Drosophila muscle to demonstrate the power of APEX for characterizing subcellular proteomes in live cells. Further, we generate "MitoMax," a database that provides an inventory of Drosophila mitochondrial proteins with subcompartmental annotation. Altogether, APEX labeling in live Drosophila tissues provides an opportunity to characterize the organelle proteome of specific cell types in different physiological conditions.
NDC80 complex (NDC80C) is composed of four subunits (SPC24, SPC25, NDC80, and NUF2) and is vital for kinetochore-microtubule (KT-MT) attachment during mitosis. Paradoxically, NDC80C also functions in ...the activation of the spindle-assembly checkpoint (SAC). This raises an interesting question regarding how mitosis is regulated when NDC80C levels are compromised. Using a degron-mediated depletion system, we found that acute silencing of SPC24 triggered a transient mitotic arrest followed by mitotic slippage. SPC24-deficient cells were unable to sustain SAC activation despite the loss of KT-MT interaction. Intriguingly, our results revealed that other subunits of the NDC80C were co-downregulated with SPC24 at a posttranslational level. Silencing any individual subunit of NDC80C likewise reduced the expression of the entire complex. We found that the SPC24-SPC25 and NDC80-NUF2 subcomplexes could be individually stabilized using ectopically expressed subunits. The synergism of SPC24 downregulation with drugs that promote either mitotic arrest or mitotic slippage further underscored the dual roles of NDC80C in KT-MT interaction and SAC maintenance. The tight coordinated regulation of NDC80C subunits suggests that targeting individual subunits could disrupt mitotic progression and provide new avenues for therapeutic intervention.
These results highlight the tight coordinated regulation of NDC80C subunits and their potential as targets for antimitotic therapies.
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•Platelets substantially contribute to the severity of epileptic seizures.•During epileptic seizures, platelets enter CNS and secrete serotonin (5-HT).•Platelet-derived 5-HT enhances ...neuronal electric activity during seizures.•Platelets stimulate neuronal synaptic activity and contribute to neuroinflammation.•Platelets induce oxidative stress in neurons during epileptic seizures.
The drugs currently available for treating epilepsy are only partially effective in managing this condition. Therefore, it is crucial to investigate new pathways that induce and promote epilepsy development. Previously, we found that platelets interact with neuronal glycolipids and actively secrete pro-inflammatory mediators during central nervous system (CNS) pathological conditions such as neuroinflammation and traumatic brain injury (TBI). These factors increase the permeability of the blood-brain barrier (BBB), which may create a predisposition to epileptic seizures. In this study, we demonstrated that platelets substantially enhanced epileptic seizures in a mouse model of pentylenetetrazole (PTZ) -induced seizures. We found that platelets actively secreted serotonin, contributed to increased BBB permeability, and were present in the CNS parenchyma during epileptic seizures. Furthermore, platelets directly stimulated neuronal electric activity and induced the expression of specific genes related to early neuronal response, neuroinflammation, and oxidative phosphorylation, leading to oxidative stress in neurons. The intracranial injection of physiological numbers of platelets that mimicked TBI-associated bleeding was sufficient to induce severe seizures, which resembled conventional PTZ-induced epileptic activity. These findings highlight a conceptually new role of platelets in the development of epileptic seizures, and indicate a potential new therapeutic approach targeting platelets to prevent and treat epilepsy.
Mechanical frothing can be used to create gas–liquid monomer foams, which can then be subsequently polymerised to produce macroporous polymers. Until recently, this technique was limited to producing ...low porosity macroporous polymers with poor pore morphology and compression properties. In this study, we show that high porosity (75–80%) biobased macroporous polymers with excellent mechanical compression properties ( E = 163 MPa, σ = 4.9 MPa) can be produced by curing of epoxy resin foams made by mechanical frothing. The key to this is to utilise the very viscous nature and very short working time of a biobased epoxy resin. It was found that increasing the frothing time of the biobased epoxy resin reduces the pore diameter of the resulting macroporous polymers. These macroporous polymers were also found to be partially interconnected. The compression properties of the macroporous polymers with smaller average pore diameter were found to be higher than those of foams with larger pore diameters. Unlike emulsion templating, which uses high internal phase emulsions to produce macroporous polymers, called polyHIPEs, the mechanical frothing technique has the advantage of creating macroporous polymers from monomers which cannot be easily emulsified.
Background
There is limited work on the impact of chemotherapy‐induced nausea and vomiting (CINV) on quality of life (QoL) in adriamycin‐cyclophosphamide (AC)–treated patients with breast cancer. The ...objectives of the study were the following: (a) to confirm if symptoms of CINV led to lower QoL during AC; (b) to evaluate the pattern of changes in patients’ QoL during multiple cycles of AC; and (c) to assess if the QoL in an earlier cycle affected the QoL in subsequent cycles of AC.
Materials and Methods
This is a secondary pooled data analysis that included 303 Chinese patients with breast cancer who received 1,177 cycles of adjuvant AC in three prospective antiemetic studies. QoL data were based on Functional Living Index–emesis (FLIE) scored over three to four AC cycles. CINV symptoms assessed included “no significant nausea” (NSN), “significant nausea” (SN), “no vomiting” (NoV), “vomiting” (V), and complete response (CR).
Results
Across all AC cycles, the mean scores for the FLIE nausea domain for patients who experienced NSN versus SN were 10.92 versus 53.92, respectively (p < .0001), with lower scores indicating better QoL; the mean scores for the FLIE vomiting domain for patients who experienced NoV versus V were 1.44 versus 19.11, respectively (p < .0001), with similar results across subsequent cycles. Analysis of the effect of the QoL in cycle 1 on the QoL of subsequent cycles revealed the following: for the nausea domain, among patients who had cycle 1 FLIE scores ≥ versus < the mean, the corresponding scores in cycle 2 were 6.87 versus 36.71 (p < .0001); whereas those for cycle 3 were 7.07 versus 36.87 (p < .0001); and those for cycle 4 were 5.92 versus 21.48 (p < .0001). Similar findings were observed for the vomiting domain. Netupitant + palonosetron– or aprepitant/olanzapine–based antiemetics had significantly better QoL outcomes.
Conclusion
CINV had a significant impact on the QoL of patients with breast cancer treated with AC over multiple cycles.
Implications for Practice
In this post‐hoc analysis of three prospective studies on chemotherapy‐induced nausea and vomiting (CINV), quality of life (QoL) using contemporary antiemetic regimens in Chinese breast cancer patients receiving doxorubicin‐cyclophosphamide (AC) was evaluated. During the first and subsequent AC cycles, QoL was significantly better for patients who did not experience vomiting or significant nausea. QoL in an earlier cycle affected the QoL in subsequent AC cycles. Furthermore, recent regimens involving olanzapine/aprepitant or netupitant‐palonosetron were associated with a positive impact in QoL. Antiemetic guideline‐consistent practice and higher clinician awareness of the impact of CINV on QoL can further mitigate the negative effects of CINV on QoL
This article focuses on chemotherapy‐induced nausea and vomiting and quality of life of breast cancer patients through multiple cycles of treatment.
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