Developing high‐efficiency and cost‐effective alloy catalysts toward hydrogen‐evolution reaction (HER) is crucial for large‐scale hydrogen production via electrochemical water splitting, but ...conventional single‐principal‐element alloy design usually causes insufficient activity and durability of state‐of‐the‐art multimetallic catalysts based on non‐precious transition metals. Herein, we report multicomponent intermetallic Mo(NiFeCo)4 nanoparticles seamlessly integrated on hierarchical nickel network (Mo(NiFeCo)4/Ni) as robust hydrogen‐evolution electrocatalysts with remarkably improved activity and durability by making use of iron and cobalt atoms partially substituting nickel sites to form high‐entropy NiFeCo sublattice in intermetallic MoNi4 matrix, which serve as bifunctional electroactive sites for both water dissociation and adsorption/combination of hydrogen intermediate and improves thermodynamic stability. By virtue of bicontinuous nanoporous nickel skeleton facilitating electron/ion transportation, self‐supported nanoporous Mo(NiFeCo)4/Ni electrode exhibits exceptional HER electrocatalysis, with low Tafel slope (≈35 mV dec−1), high current density (≈2300 mA cm−2) at low overpotential (200 mV) and long‐term durability in 1 m KOH. When coupled to its electrooxidized and nitrified derivative for oxygen‐evolution reaction, their alkaline water electrolyzers operate with a superior overall water‐splitting output, outperforming the one constructed with commercially available noble‐metal‐based catalysts. These electrochemical properties make it an attractive candidate as electrocatalyst in alkaline water electrolysis for large‐scale hydrogen generation.
Multicomponent intermetallic Mo(NiFeCo)4 nanoparticles that are seamlessly integrated on hierarchical nanoporous nickel network (Mo(NiFeCo)4/Ni) hold great promise as low‐cost verstile electrocatalysts for highly efficient water splitting. Associated with hierarchical nanoporous architecture to facilitate electron transfer and offer abundant multicomponent intermetallic active sites, the self‐supported nanoporous Mo(NiFeCo)4/Ni electrode and its electrooxidized/nitrified derivative exhibit remarkably enhanced hydrogen‐evolution and oxygen‐evolution activities and durability.
Ubiquitin-conjugating enzyme E2C (UBE2C) has been shown to be associated with the occurrence of various cancers and involved in many tumorigenic processes. This study aimed to investigate the ...specific molecular mechanism through which UBE2C affects breast cancer (BC) proliferation.
BC-related datasets were screened according to filter criteria in the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database. Then differentially expressed genes (DEGs) were identified using Venn diagram analysis. By using DEGs, we conducted the following analyses including Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI), and survival analysis, and then validated the function of the hub gene UBE2C using quantitative reverse transcription-polymerase chain reaction (RT-qPCR), cell counting kit-8 (CCK-8) assay, transwell assay, and Western blot assay.
In total, 151 DEGs were identified from the GEO and TCGA databases. The results of GO analysis demonstrated that the DEGs were significantly enriched with mitotic nuclear division, lipid droplet, and organic acid-binding. KEGG analysis showed that the peroxisome proliferators-activated receptor (PPAR) signaling pathway, regulation of lipolysis in adipocytes, and proximal tubule bicarbonate reclamation were significantly enriched in the signal transduction pathway category. The top three hub genes that resulted from the PPI network were FOXM1, UBE2C, and CDKN3. The results of survival analysis showed a close relationship between UBE2C and BC. The results of CCK-8 and transwell assays suggested that the proliferation and invasion of UBE2C knockdown cells were significantly inhibited (P < 0.050). The results of Western blot assay showed that the level of phosphorylated phosphatase and tensin homology deleted on chromosome 10 (p-PTEN) was obviously increased (P < 0.050), whereas the levels of phosphorylated protein kinase B (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR), and hypoxia-inducible factor-1 alpha (HIF-1α) were dramatically decreased (P < 0.050) in the UBE2C knockdown cell.
UBE2C can promote BC proliferation by activating the AKT/mTOR signaling pathway.
Procyanidins (PCs), which are organic antioxidants, suppress oxidative stress, exhibit anti-apoptotic properties, and chelate metal ions. The potential defense mechanism of PCs against cerebral ...ischemia/reperfusion injury (CIRI) was investigated in this study. Pre-administration for 7 days of a PC enhanced nerve function and decreased cerebellar infarct volume in a mouse middle cerebral artery embolization paradigm. In addition, mitochondrial ferroptosis was enhanced, exhibited by mitochondrial shrinkage and roundness, increased membrane density, and reduced or absent ridges. The level of Fe
and lipid peroxidation that cause ferroptosis was significantly reduced by PC administration. According to the Western blot findings, PCs altered the expression of proteins associated with ferroptosis, promoting the expression of GPX4 and SLC7A11 while reducing the expression of TFR1, hence inhibiting ferroptosis. Moreover, the treatment of PCs markedly elevated the expression of HO-1 and Nuclear-Nrf2. The PCs' ability to prevent ferroptosis due to CIRI was decreased by the Nrf2 inhibitor ML385. Our findings showed that the protective effect of PCs may be achieved via activation of the Nrf2/HO-1 pathway and inhibiting ferroptosis. This study provides a new perspective on the treatment of CIRI with PCs.
In China, medical staff of children's hospitals are commonly exposed to violence. However, few studies on medical violence are conducted in the settings of children's hospitals. The aim of this study ...is to assess the incidence, magnitude, consequences, and potential risk factors of workplace violence (WPV) against medical staff of children's hospitals.
A retrospective cross-sectional design was used. A self-administered questionnaire was utilized to collect data on 12 children's hospitals. The questionnaires were distributed to a stratified proportional random sample of 2,400 medical staff; 1,932 valid questionnaires were collected. A chi-square test and multiple logistic regression analysis were conducted.
A total of 68.6% of respondents had experienced at least one WPV incident involving non-physical and/or physical violence in the past year. The perpetrators were mainly family members of patients (94.9%). Most of the WPV occurred during the day shift (70.7%) and in wards (41.8%). Males were 1.979 times (95% CI, 1.378 to 2.841) more likely than females to experience physical violence. Emergency departments were more exposed to physical violence than other departments. Oncology was 2.733 times (95% CI, 1.126 to 6.633) more exposed to non-physical violence than the emergency department. As a result of WPV, victims felt aggrieved and angry, work enthusiasm declined, and work efficiency was reduced. However, only 5.6% of the victims received psychological counseling.
Medical staff are at high risk of violence in China's children's hospitals. Hospital administrators and related departments should pay attention to the consequences of these incidents. There is a need for preventive measures to protect medical staff and provide a safer workplace environment. Our results can provide reference information for intervention strategies and safety measures.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The purpose of this study was to assess the value of metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) for the diagnosis of severe respiratory diseases based on ...interpretation of sequencing results. BALF samples were harvested and used for mNGS as well as microbiological detection. Infectious bacteria or fungi were defined according to relative abundance and number of unique reads. We performed mNGS on 35 BALF samples from 32 patients. The positive rate reached 100% in the mNGS analysis of nine immunocompromised patients. Compared with the culture method, mNGS had a diagnostic sensitivity of 88.89% and a specificity of 74.07% with an agreement rate of 77.78% between these two methods. Compared with the smear method and PCR, mNGS had a diagnostic sensitivity of 77.78% and a specificity of 70.00%. In 13 cases, detection results were positive by mNGS but negative by culture/smear and PCR. The mNGS findings in 11/32 (34.4%) cases led to changes in treatment strategies. Linear regression analysis showed that diversity was significantly correlated with interval between disease onset and sampling. Dynamic changes in reads could indirectly reflect therapeutic effectiveness. BALF mNGS improves sensitivity of pathogen detection and provides guidance in clinical practice. Potential pathogens can be identified based on relative abundance and number of unique reads.
Hypoxemia frequently occurs during bronchoscopy. High-flow nasal cannula (HFNC) oxygen therapy may be a feasible alternative to prevent the deterioration of gas exchange during bronchoscopy. With the ...convenience of clinical use in mind, we modified an HFNC using a single cannula. This clinical trial was designed to test the hypothesis that a modified HFNC would decrease the proportion of patients with a single moment of peripheral arterial oxygen saturation (SpO
) < 90% during bronchoscopy.
In this single-center, prospective randomized controlled trial, hospitalized patients in the respiratory department in need of diagnostic bronchoscopy were randomly assigned to a modified HFNC oxygen therapy group or a conventional oxygen therapy (COT) group. The primary outcome was the proportion of patients with a single moment of SpO
< 90% during bronchoscopy.
Eight hundred and twelve patients were randomized to the modified HFNC (n = 406) or COT (n = 406) group. Twenty-four patients were unable to cooperate or comply with bronchoscopy. Thus, 788 patients were included in the analysis. The proportion of patients with a single moment of SpO
< 90% during bronchoscopy in the modified HFNC group was significantly lower than that in the COT group (12.5% vs. 28.8%, p < 0.001). There were no significant differences in the fraction of inspired oxygen between the two groups. The lowest SpO
during bronchoscopy and 5 min after bronchoscopy in the modified HFNC group was significantly higher than that in the COT group. Multivariate analysis showed that a baseline forced vital capacity (FVC) < 2.7 L (OR, 0.276; 95% CI, 0.083-0.919, p = 0.036) and a volume of fluid instilled > 60 ml (OR, 1.034; 95% CI, 1.002-1.067, p = 0.036) were independent risk factors for hypoxemia during bronchoscopy in the modified HFNC group.
A modified HFNC could decrease the proportion of patients with a single moment of SpO
< 90% during bronchoscopy. A lower baseline FVC and large-volume bronchoalveolar lavage may predict desaturation during bronchoscopy when using a modified HFNC. Trial registration ClinicalTrials. Gov: NCT02606188. Registered 17 November 2015.
The effects of key parameters on locked mode induced disruption (LMiD) are investigated in EAST experiments. The experimental data for locked mode are collected from 2015 to 2022 when the externally ...applied resonant magnetic perturbation is successfully employed in EAST. In this dataset, ∼42% of the total shots are LMiD, while the remaining 58% are LM without disruption. To better analyze the LMiD, an intuitive physical process is proposed. The LMiD process can be divided into two stages, the evolution of magnetic islands and the loss of plasma stored energy. The LMiD can also be related to the evolution of the other 8 physical quantities. On the basis of this physical process analysis, the time scale and the influencing factors for LMiD are investigated using statistical analysis. It is found that the density (ne), the distance from the magnetic island outer boundary to the plasma last closed surface (dedge), the loop-voltage (Vloop), and the plasma core electron temperature (Te), which are consistent with the intuitive physical model, are key parameters to LMiD. In addition, other potentially important parameters, the relevant reasons, and statistical analysis on the parameter intervals where rapid disruption with greater harmfulness occurred have also been investigated.
Abstract
Background
Pneumocystis
pneumonia (PCP) is a life-threatening opportunistic fungal infection with a high mortality rate in immunocompromised patients, ranging from 20 to 80%. However, ...current understanding of the variation in host immune response against
Pneumocystis
across different timepoints is limited.
Methods
In this study, we conducted a time-resolved single-cell RNA sequencing analysis of CD45
+
cells sorted from lung tissues of mice infected with
Pneumocystis
. The dynamically changes of the number, transcriptome and interaction of multiply immune cell subsets in the process of
Pneumocystis
pneumonia were identified according to bioinformatic analysis. Then, the accumulation of Trem2
hi
interstitial macrophages after
Pneumocystis
infection was verified by flow cytometry and immunofluorescence. We also investigate the role of Trem2 in resolving the
Pneumocystis
infection by depletion of Trem2 in mouse models.
Results
Our results characterized the CD45
+
cell composition of lung in mice infected with
Pneumocystis
from 0 to 5 weeks, which revealed a dramatic reconstitution of myeloid compartments and an emergence of PCP-associated macrophage (PAM) following
Pneumocystis
infection. PAM was marked by the high expression of Trem2. We also predicted that PAMs were differentiated from Ly6C
+
monocytes and interacted with effector CD4
+
T cell subsets via multiple ligand and receptor pairs. Furthermore, we determine the surface markers of PAMs and validated the presence and expansion of Trem2
hi
interstitial macrophages in PCP by flow cytometry. PAMs secreted abundant pro-inflammation cytokines, including IL-6, TNF-α, GM-CSF, and IP-10. Moreover, PAMs inhibited the proliferation of T cells, and depletion of Trem2 in mouse lead to reduced fungal burden and decreased lung injury in PCP.
Conclusion
Our study delineated the dynamic transcriptional changes in immune cells and suggests a role for PAMs in PCP, providing a framework for further investigation into PCP’s cellular and molecular basis, which could provide a resource for further discovery of novel therapeutic targets.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Stroke is one of the leading causes of death and long-term disability worldwide. More than 80 % of strokes are ischemic, caused by an occlusion of cerebral arteries. Without question, restoration of ...blood supply as soon as possible is the first therapeutic strategy. Nonetheless paradoxically, reperfusion can further aggravate the injury through a series of reactions known as cerebral ischemia-reperfusion injury (CIRI). Mitochondria play a vital role in promoting nerve survival and neurological function recovery and mitochondrial dysfunction is considered one of the characteristics of CIRI. Neurons often die due to oxidative stress and an imbalance in energy metabolism following CIRI, and there is a strong association with mitochondrial dysfunction. Altered mitochondrial dynamics is the first reaction of mitochondrial stress. Mitochondrial dynamics refers to the maintenance of the integrity, distribution, and size of mitochondria as well as their ability to resist external stimuli through a continuous cycle of mitochondrial fission and fusion. Therefore, improving mitochondrial dynamics is a vital means of treating CIRI. This review discusses the relationship between mitochondria and CIRI and emphasizes improving mitochondrial dynamics as a potential therapeutic approach to improve the prognosis of CIRI.
Display omitted
•The physiopathological mechanisms of cerebral ischemia-reperfusion injury are elaborated.•The role of mitochondria in cerebral ischemia-reperfusion injury is discussed.•The strategy proposed that mitochondrial dynamic may be the therapeutic target of cerebral ischemia-reperfusion injury.
Developing robust nonprecious metal‐based electrocatalysts toward hydrogen evolution reaction is crucial for large‐scale hydrogen production via electrochemical water splitting. Herein, surface ...high‐entropy NiFeCoCuTi alloy on column‐nanostructured nanoporous Ni skeleton is reported as multisite electrocatalyst for highly efficient hydrogen evolution in nonacidic environments by making use of surface heterogeneous atoms with distinct hydrogen and hydroxyl adsorption behaviors to accelerate water dissociation and mediate adsorption of hydrogen intermediates for combination into molecules. Associated with the column‐nanostructured nanoporous Ni skeleton that facilitates electron transfer/mass transportation and enables highly accessible and abundant electroactive sites, self‐supported monolithic nanoporous high‐entropy NiFeCoCuTi alloy electrode exhibits superior nonacidic hydrogen evolution reaction (HER) electrocatalysis, with low onset overpotentials and Tafel slopes. It only takes overpotential of as low as ≈209 mV to deliver ultrahigh current density of 2 A cm
−2
, along with exceptional stability for more than 240 h, in 1
m
KOH electrolyte. These outstanding properties make nanoporous NiFeCoCuTi high‐entropy alloy (HEA) electrode attractive candidate as cathode material in the water electrolysis for large‐scale hydrogen production and suggest HEAs as ideal platform to develop multisite electrocatalysts.
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